General Embryology, Organogenesis and Organ structure

Spermiogenesis

spermatids become sperm

In the basal compartment we find:

spermatogonia and early primary spermatocytes

Basal compartment and adluminal compartment separated by junctional processes (tight junctions) formed by

SERTOLI CELLS

What is an example of how immune-tolerance is established?

An example of how immune tolerance is established is when during the second phase of the menstrual cycle some leukocytes invade the endometrium and they do it because if the blastocyst is ready to implant the leukocytes start producing factors like interleukin 2 which is a cytokine that prevents the recognition of the embryo as a foreign body.

The embryo is a

curved object that changes its shape over time.

germ cells (gametes)

sex cells (sperm = in testes and egg = in ovaries).

Some primary follicles proceed...

their development and become late primary follicles or farther growing follicles, while others die.

System of vessels which is around the vitelline sac:

vitelline vein and vitelline artery.

List the key components of the female reproductive system:

(1) Vagina ● the lower part of the female reproductive tract: a muscular tube, lined with mucous membrane, connecting the cervix of the uterus to the exterior. It receives semen that is ejaculated into the upper part of the vagina and from there the sperms must pass through the cervix and uterus to fertilize an ovum in the Fallopian tube. (2) Cervix ● the lower third of the Uterus, being a small neck shaped connective canal which links the cavity of the uterus with the vagina. The canal is lined with mucous membrane and normally contains mucus, the viscosity of which changes throughout the menstrual cycle. The cells are stratified columnar epithelium. (3) Uterus ● (womb) a pear-shaped organ that is about 3 inches (7.5cm). Suspended in the pelvic cavity by peritoneal folds (ligaments) and fibrous bands. The upper two thirds are connected to the fallopian tubes, whilst the lower third being the Cervix projects into the vagina. (4) Fallopian tubes ● a pair of tubes that conduct ova from the ovaries to the uterus. The ovarian end opens into the abdominal cavity with a funnel shaped structure with fine finger-like projections called Fimbriae. (5) Fimbriae ● Finger-like projects located at the ovary side of the fallopian tubes. The movement of the projections at ovulation assist in directing the ovum to the fallopian tube. (6) Ovary ● there are two ovaries, one of each located at the lateral end of each fallopian tube within the abdominal cavity. Each ovary contains numerous primary follicles. As a result of hormone production during the menstrual cycle, a few follicles will mature, with a mature Graafian follicle releasing an ovum during ovulation. After the release of the ovum, the remainder of the Graafian Follicle, reseals and becomes a young corpus luteum, releasing progesterone, in preparation for a potential fertilization event to occur.

What is the amnion?

(outer layer of the amniotic sac) contains amniotic fluid that cushions and protects the embryo.

What is gastrulation and when does it occur?

-Gastrulation is when some cells start to proliferate from the epiblast, and then underneath the epiblast will be formation of other layer of cells which forms the Mesoderm. -the process that establishes the three definitive germ layers of embryo (ectoderm, intraembryonic mesoderm, and endoderm), thereby forming a trilaminar embryonic disk by day 21 of development -occurs in week 3 (by day 21) Cells of the epiblast, which are differentiated forming an epithelial layer, undergo a process of dedifferentiation and start to migrate towards the primitive streak and when they reach it, either the groove or the pit within the node, they enter into it, so they invaginate. → Differentiated epithelial cells cannot move around because for example there are junctions between the cells and there's polarization of the membrane: they undergo an epithelial-mesenchymal transition and once they reach a certain place they go through a mesenchymal-epithelial transition (Mesenchymal cells are very undifferentiated precursors of connective tissue cells). → This transition is guided by a lot of molecular factors, for example by fibroblast growth factor which is a signaling molecule. → There are changes from cell-to-cell adhesion, typical of a differentiated epithelium, to cell-to-substrate adhesion: if a cell wants to move around in the body it must lose contact with the other epithelial cells and attach progressively for example to extracellular matrix. → The shape and the cytoskeletal organization of the cells changes: in order to invaginate in the primitive streak, they have to move by adhering to substrates, but they also form cytoplasmic projections.

Are the organs functional during the fourth week period?

1. During this period the organ function is minimal except for the cardiovascular system because up to a certain point the embryo is nursed by diffusion from the maternal blood in the lacunae but then it becomes quite big and it needs a cardiovascular system. 2. This cardiovascular system, even if it is quite simple and still embryonal, has to be working properly.

What do we see in this image of the folding in the region of the heart tubes?

1. On the diagram below, image (B) shows the tubes one on the right and one on the left. 2. Then they get closer to one another in (C) because of the folding of the embryo. 3. In (D) they fuse together to form a single tubular heart.

Summary of how the mesoderm is divided:

1. Parietal layer (close to the body wall): somatopleure 2. Visceral layer (close to the intestinal tube): splanchnopleure ("splancho" refers to viscera)

What does the follicular fluid in the antrum contain?

1. 20 enzymes 2. Dissolved hormones (LH, FSH, steroids) 3. Negatively charged proteoglycans (which attract water and increase size of antrum)

What else, other than the production of factor motlity protein, occurs during the maturation of spermatozoa?

1. A cascade of events that trigger and regulate the motility of the flagellum 2. While the spermatozoa are residing in the epididymis some biochemical changes occur. E.g. the head of the spermatozoa is coated by a glycoprotein. 3. When the spermatozoa are inside the female genital tract, this coating has to be removed for the spermatozoa to be able to fertilize the egg

What is an example of a teratogen that can affect the development of the embryo in the 4th week?

1. A drug that can cause problems in the development of the embryo when taken by pregnant women very early is thalidomide. 2. It is a drug used in the 50s and in the 60s to prevent nausea during pregnancy. 3. After a while it was discovered that mothers who took the drug early on in the pregnancy would give birth to babies with very poorly developed upper (more frequent if taken during the fourth week) or lower (more frequent if taken during the fifth week) limbs, or both of them. 4. The testing of that drug hadn't been done on pregnant animals; that's why nowadays it's mandatory to test drugs on pregnant animals as well in order to know the possible collateral effects on fetuses.

Male infertility could be associated to:

1. A reduced number of spermatozoa (less than 10 million x milliliter) - their likelihood of survival inside the female tract is very slim. 2. Lack of motility 3. Abnormal sperms - even in a perfectly fertile male there are some abnormal spermatozoa (e.g. with a double head, a double tail, problems in the division of the initial part of the flagellum) 4. Genomic alteration 5. Medications or drugs - substances that can go through the blood-testis barrier or can reach the spermatogonia and affect either only the spermatogonia or the spermatocytes as well (this can reduce motility) 6. Endocrine disorders - the harmony of the hormonal control is disrupted 7. Environmental pollutants - can reach seminiferous tubules and affect the motility of the spermatozoa 8. Cigarette smoking 9. Obstruction of the genital duct system - for example, inflammation caused by STDs which causes scarring can cause a block

To be functionally mature for fertilization the sperm must be:

1. Actively motile Have to be able to swim spontaneously towards the oocyte even though the female genital tract helps, with the contraction of the uterine wall, to propel the spermatozoa towards the uterine tubes (aka. fallopian tube -- Barajon uses uterine tube interchangeably for fallopian tube). 2. Able to recognise the oocyte Have to be able to connect with the oocyte 3. Able to pass across the membrane of the oocyte Not only the plasma membrane, but all the cells that surround it

What happens after luteinization?

1. After luteinization we are now able to see granulosa lutein and theca lutein cells. 2. These cells of the corpus luteum produce progesterone (in much higher amounts) and oestrogens. 3. These hormones are important in the preparation of the endometrium and the mucosa of the uterine tubes (aka. fallopian tubes) for a possible pregnancy. 4. Progesterone is especially important; in fact, the second phase of the menstrual cycle is also called the progestinic phase, while the first phase before ovulation is also called the estrogenic phase of the cycle. 5. The corpus luteum is functional for about 2 weeks after ovulation. After this there are two options...

How the corpus luteum is formed: What is the Luteinization?

1. After this short moment in which it is the corpus haemorragicum, this body of cells transforms in a process called Luteinization, in which cells that belong to the granulosa and to the theca interna undergo some changes: there is an accumulation of lipid droplets, an increase of cell size, the structure becomes steroid producing and richly vascularized. 2. This is because it acts as an endocrine gland and needs to secrete its products in the bloodstream.

Early stages of cardiovascular system formation (development of the heart to understand the process of folding). How is the cardiovascular system formed?

1. Among the cells that migrated through the primitive streak, there are the cells that are going to give rise to the primary heart field. 2. These cells migrate through the primitive streak and go rostrally and position themselves in the region of the lateral plate mesoderm, where the splanchnopleure is being formed. 3. Due to their organisation, they form what we call the cardiac crescent, a curved shaped area. Very early on, the mesenchymal cells of the cardiac crescent on the right and on the left change and form two endocardial tubes, one of the left and one on the right.

What are Sertoli Cells?

1. An important structural element of the seminiferous tubule is represented by Sertoli cells, which are somatic cells of the testis. 2. We highlighted the importance of Sertoli cells to form the blood-testis barrier, creating in the wall of the seminiferous tubules a basal compartment to be separated from the adluminal compartment, where spermatocytes entering the meiotic cycle become antigenically different. Cells that fill gaps between spermatogenic cells, but they also serve many other purposes in spermatogenesis.

How is the spermatozoon nucleus decondensed?

1. An increase in the permeability of the nuclear membrane of the spermatozoon 2. Removal of protamines that were keeping the genetic material together 3. Spreading of chromatin of the male chromosomes to allow the mechanisms of duplication to begin 4. Demethylation of paternal DNA, which allows the increased contact with the female genetic material. This is because when the gametes were formed, much methylation(mechanism that impedes the transcription of the genetic material) was going on. Now that the paternal genetic material has entered the oocyte, it must be demethylated to be more available to come into contact with the female genetic material. Up until this point there are two polar bodies: one coming from meiosis I and one from the second meiotic division. If the second one manages to undergo meiosis, we may have the formation of a third polar body, but not necessarily.

During the fourth week, what is established?

1. During the fourth week, the organs' plan is developing as well (organogenetic period = organogenesis = organs are established). 2. During the fourth week the body plan is established, meaning this week marks the beginning of the organogenetic period which lasts up to the eighth week. 3. All major internal and external structures of the embryo are roughly established during this window of time (the blueprint of the rudiments of the organs are established).

What is another example of the molecules being swept from the right to the left?

1. Another example of the molecules which are swept from the right to the left is serotonin (5HT). 2. This is one of the neurotransmitters of the nervous system and is also one of the molecules present during development that are swept on the left side. 3. At some point it'll be more concentrated on the left side because on the right side there's a higher concentration of the enzyme that degrades serotonin as well, also known as MAO (mono-amine oxidator enzyme). 4. For this reason we need to pay attention if a pregnant woman uses some antidepressants which act as MAO inhibitors. Using MAO inhibitors during the early stages of pregnancy can cause a greater than usual concentration of serotonin on the right side (because serotonin it's not degraded by MAO). This is a typical example of why pregnant women have to be very careful with what they eat and take as far as medication, especially during early stages of pregnancy.

What are the apposition & adhesion stages of implantation of the blastocyst?

1. Apposition of the blastocyst can only occur in the period of time known as the "implantation window" = the endometrium is not in the right stage of the implantation to take place. This reception-ready phase of the endometrium lasts 4 days, and comes 6 days after the LH peak. 2. During this phase the mucosa of the uterus is really ready for implantation. 3. If adhesion doesn't take place the blastocyst can still be washed away.In this stage the blastocyst can still be eliminated by being flushed out (flushed out = blastocyst is not attached at the apposition stage).

Meiosis in males (how many days the separate processes last):

1. Asynchronous 2. 1st meiotic division lasts 24 days 3. 2nd meiotic division 8 hours Spermiogenesis 24 days Total 48 days In the broadest sense spermatogenesis begins with proliferation of spermatogonia (16 days) Grand total: around 64 days

What happens during the fifth phase of fertilization?

1. At fertilization there is the completion of meiosis II and the formation of the second polar body. 2. Remember that the cytoplasm of the oocyte when dividing cannot be shared because it is needed for the embryo and so the second cell produced by meiosis is a polar body. 3. There is also the metabolic activation of the egg; all of the material that can sustain the development of the embryo comes from the oocyte, none of it is contributed by the spermatozoon. 4. All of the years that the oocyte was in the ovary before meiosis II was spent gathering materials such as mRNA. During this metabolic process maternal mRNA becomes active (is recruited) and many metabolic changes take place in the oocyte because of the addition of spermatozoon genetic material. 5. The oocyte gets ready for the fusion of the two types of genetic material and sustains the beginning of pregnancy. The maternal genetic material supports the embryo in the stages before the DNA of the new forming human is able to be used for transcription. 6. At this point there are two nuclei in the oocyte(the one of the oocyte and the one of the spermatozoon) Before fertilization, the genetic material of the sperm was incredibly compacted to allow it to travel, and so once fertilization has occurred there needs to be a decondensation (needs to be unpacked, because how can the chromosomes be compact when they need to replicate) of spermatozoon nucleus.

To summarize the production of amniotic fluid:

1. At the beginning it is a transudate that comes from the maternal blood vessels from different sources 2. But then, at some point, the embryo starts to develop a urinary system and kidneys and starts to produce a prequitive urine (not the urine that we produce as adults which contain a lot of wastes, but it is a watery mean, because the wastes are eliminated by the placenta). When we reach the latest stages of pregnancy the can be up to half a liter (1000mL) per day.

ONLY ONE of the growing antral follicle will continue its maturation

1. At the beginning of the cycle follicles start maturation from the primordial follicle, as many as 50, but only around 3 attain a size of 8mm. 2. The initial growth of the follicles is hormone independent. If you look at the graph, the dashed line is FSH and the continuous line is LH. At the beginning of the cycle both are very low. 3. Then if some of these follicles want to keep maturing they need a minimum tonic level of FSH (a bit higher in production). 4. At some point one of these large follicles - a dominant large follicle becomes independent from FSH and secretes inhibin. 5. Inhibin goes back to the adenohypophysis where it inhibits the production of FSH (reduction of FSH), so the other follicles still depending on FSH degenerate and die (FSH-dependent die).

What is the amniotic fluid at the beginning?

1. At the beginning the amniotic fluid is a transudate of maternal plasma through the decidua parietalis (endometrium after the changes through which it has undergone after the implantation of the blastocyst). 2. The decidua can be divided into territories: there is the decidua basalis which is where the blastocyst implants on the site of the implantation of the blastocyst; when it has implanted the endometrium surrounds the blastocyst and that is the decidua capsularis; then the blastocyst starts to protrude into the uterine cavity and still has a covering membrane on it and that is the decidua capsularis; the rest of the decidua is called the decidua parietalis. 3. This one at the beginning of the developmental story starts to produce a fluid which contributes to the formation of the amniotic fluid. 4. Later there will be a contribution from the chorionic plate, the mesodermal layer of the chorion. 5. From the 11th week there is the addition of fetal urine

What happens in the beginning of establishing the body axes?

1. At the beginning there are some factors that are expressed throughout the embryonic disk but then we have a repression of the primitive streak expression in the rostral part of the embryo because of the activity of the region that corresponds to the anterior visceral endoderm. 2. In the caudal part, instead, this expression remains and therefore contributes to establishing the rostral-caudal axis. 3. Within the future body of the embryo there are three organizing regions (these regions sometimes are real morphological regions): head, trunk and tail organizers.

Sperm Transport and Maturation:

1. During the process of intercourse there is the moment of ejaculation, the sperm that were inside the epididymis (that were maturing) are ejected rapidly through the ductus deferens and urethra. 2. Whilst traveling along the urethra, substances are added to the semen from specialized glands, the prostate which contributes acidic secretions (citric acid, acid phosphates, magnesiums and zinc) and the seminal vesicles which contribute sugars in the form of fructose as a source of energy for the spermatozoa and this secretion is weakly basic. 3. To reiterate, the majority of the seminal fluid is made of glandular secretions whilst only a small portion consists of the spermatozoa.

What do we see at this stage of development of the embryo?

1. At the level of the cytotrophoblast something is changing, it is forming a sort of crown in it, because all around the chorionic cavity, the cytotrophoblast starts to proliferate, forming these sort of protrusions, projections, that at this level are called primary villi, made only of cytotrophoblast. 2. They will eventually form the chorionic villi, which form from the components of the chorion. These villi will grow more on the side of the embryo, and in that region they take the name of chorion frondosum (trees with a lot of branches). On the other side, the abembryonic pole, the chorion laeve (light) will form. The most important villi, where the capillary network will form, are the ones on the side of the embryo, belonging to the chorion frondosum. 3. So at this stage of development we find the embryo suspended inside the chorionic cavity, while the chorion is changing, with its different villi, more branched in the chorion frondosum and less branched in the chorion laeve.

Clinical drop: Mittelschmerz

1. At the moment of ovulation there may be some form of abdominal/pelvic pain known as Mittleschmerz. 2. Ovulation is considered a trauma to the surface of the ovary and there is an irritation of the serosa, which lines the abdominal and peritoneal cavity, due to any blood that may enter these spaces.

Why is a parasitic relationship?

1. Because basically the embryo needs the mother to acquire oxygen and nutrients and eliminate wastes. It can not do these on its own. 2. And also the embryo and then the fetus must avoid to be rejected as a foreign body, because we have said that the fetus is a part of it = it is recognized by the maternal immune system as proper (the rest has the paternal genome and is recognized as foreign). 3. Nourishment, elimination of wastes and avoidance of rejection are fulfilled by the placenta and the extraembryonic membranes that surround the embryo and serve as an interface with the mother.

What happens to the septum transversum with the folding of the embryo?

1. Because of the rostral fold the septum transversum ends up centrally, which now lies caudal to the heart, in fact it's an important component of the diaphragm. 2. Its repositioning causes the separation of the coelomatic cavity in a thoracic portion and abdominal portion. Up to this moment the cavity is continuous, there is no separation between what is going to become the thorax or the abdominal cavity. 3. There is a separation but there are also structures that pass through, like the aorta, the inferior vena cava, the esophagus, so it's not a complete closure. 4. We can see the heart is above the diaphragm. The heart lies above the tendinous center of the diaphragm, thet is the portion of it that generates from the septum transversum.

What distinguishes meiosis in females?

1. By the 5th month of fetal gestation all oogonia begin meiosis and they are called primary oocytes. 2. Meiosis begins as a synchronous process, as all oogonia enter meiosis I in the 5th month. 3. Then the process is slow-paced (some primary oocytes are stuck in meiosis I until menopause). 4. Meiosis I is completed at ovulation. 5. Meanwhile a supportive follicle complex is developed and a lot of material is accumulated in the cytoplasm, in case the oocyte is fertilized and has to complete also meiosis II.

What does capacitation involve?

1. Capacitation process occurs in the female genital tract. 2. The spermatozoa which reside for short amounts of time in the female genital tract are not as capacitated as those who reside there longer 3. Poorly able to fertilize = the spermatozoa that reach the oocyte too quickly are unlikely to fertilize the egg 4. Important to allow the acrosomal reaction (which consists in the exocytosis of hydrolytic enzymes) -- The acrosome contains enzymes. When these enzymes are released upon contact between the spermatozoa and the oocyte, there is an acrosomal reaction, meaning the enzymes from the acrosome can help digest what surrounds the oocyte so the spermatozoa can go through the membrane and the nucleus 5. Capacitation is associated with the removal of sperm plasma membrane proteins, reorganisation of plasma membrane lipids and proteins -- In the female genital tract the plasma membrane of the spermatozoa is changed. Some antigenic domains of the membrane are changed and the glycoproteins which are added when the spermatozoa was inside the epididymis are mostly removed. -- This makes the head of the spermatozoa more able to perform its function

What do we find in the caudal region of the embryonic disk?

1. Caudal region of the embryo: we find the remains of the primitive streak, which is regressing very caudally. 2. We also find the cloacal membrane, which is like the oropharyngeal membrane and is a region of the disk where the mesoderm does not migrate and is the region where the future anal pit and external openings of the genital tracts and digestive tracts will form. 3. We also see the connecting stalk, which is the extraembryonic mesoderm which serves as a peduncle holding together the embryo with the amniotic sac and the yolk sac inside the chorionic cavity. 4. We also see something that we never mentioned, the allantois, which is the extension of the yolk sac within the connecting stalk. From the functional point of view, the allantois is not so important in humans, just mostly in the development of the urinary system.

What is cleavage?

1. Cleavage is part of the early development of the embryo = the process in which the cell will no longer be unicellular. The zygote goes through many cell divisions where it splits but does not grow. 2. Cleavage begins 30 hours after fertilization; the zygote, which is still contained in the zona pellucida, increases its cell number without increasing its overall size. 3. The whole process takes place in the fallopian tube to then reach the uterine tube. In mammals this process takes days. Mammalian cleavage is a "leisurely" process: it takes days and not hours.

What are Type A and Type B spermatogonia and spermatocytes? Explain the process of Spermatogenesis:

1. During the spermatogonial phase, primordial spermatogonia (type A dark spermatogonia), give rise to cells committed to differentiation (type A pale), connected by cytoplasmic bridges. 2. Type A pale spermatogonia evolve in differentiating spermatogonia (type B), which enter the meiotic process (proper spermatogenesis). 3. Type B spermatogonia give rise to primary spermatocytes that enter meiosis I. 4. During meiosis I, primary spermatocytes leave the basal compartment and migrate to the adluminal compartment. 5. Meanwhile, for the following 24 days, mRNA proteins are synthetized. 6. After meiosis I, primary spermatocytes remain interconnected and immediately enter meiosis II, with the name of secondary spermatocytes. 7. Meiosis II lasts 8 hours. At this point, spermatocytes are called spermatids. 8. Throughout spermatogenesis, spermatogonia, spermatocytes, and spermatids stay connected by cytoplasmic bridges. 9. These bridges are lost when spermatids are released in the lumen of the seminiferous tubules, where they are still infertile and not motile.

What do we see in this image?

1. Colored in light blue is the septum transversum. (Picture B) we can see that at the beginning the separation between the rostral and caudal part is not completed because posteriorly there's still a communication (blue arrow). 2. The communication is called pericardio-peritoneal canal. Then the canals disappear when the diaphragm is completed. The diaphragm at the beginning is quite rostral, is at the cervical level, but then the body of the embryo elongates and the diaphragm becomes more caudal (lombar level). The diaphragm is inserted between the L1 and L2 vertebrae. This is interesting because next semester we will study that the diaphragm is innervated by the phrenic nerve, that is the largest terminal branch of the cervical plexus. That's because at the beginning the diaphragm is quite rostral and the neural connections are established at the time from the section of the spinal cord that is closer to it. 3. Then when the embryo elongates, that connection is maintained and the phrenic nerve elongates too following the development of the diaphragm. One of the problems with lesions of the upper cervical segment of the spinal cord is that you have serious problems in breathing. 4. In the thoracic portion of the ceolomatic cavity we have the formation of the pleura-pericardial cavity (the serosal spaces that surround the lungs and the heart) while the abdominal portion will become the peritoneal cavity.

So the initial content of the umbilical cord is represented by:

1. Connecting stalk, with allantois and umbilical vessels 2. Vitelline duct, with the vitelline vessels that from the vitelline sac go back and forth the embryo's body; 3. Extraembryonic coelom, initially it is contained inside the umbilical cord 4. Intestinal loop (from 6 to 10 week): for a while in the umbilical cord we can find part of the midgut. This concept will be clearer when we discuss the development of the digestive tract. Part of the midgut herniates outside of the body cavity inside the umbilical cord. That is because the intestine is pretty long, with many loops. During development, in order for this intestine to grow so much, it needs to go outside the abdominal cavity, because there isn't enough space. It elongates, and then can go back and reposition itself in the correct place within the abdominal cavity (if everything goes right).

Once the blastocyst has implanted, different regions of the decidua take different names:

1. Decidua capsularis (coating, capsule): is the decidua that covers that chorionic cavity. This layer of decidua will degenerate around the third month, because it is too stretched from the growth of the chorionic cavity. 2. Decidua basalis: it is on the side of the embryo 3. Decidua parietalis: on the side not occupied by the embryo

What, related to the sperm structure leads to male infertility?

1. Deficiency in the axonemal structure causes defects in sperm motility, and often leads to sperm infertility. 2. Infertility might also be determined by damaged motile cilia. These cilia are located in the ductus deferens and help the circulation of spermatozoa. 3. Sometimes they lose their ability to be motile (ciliopathy), leading to infertility. The image shows the distribution of motile cilia in the human body. Tissues or organs with motile cilia are shown with their types (monocilia or multicilia) and internal structures.

Twinning can be:

1. Dizygotic (twins) 2. Monozygotic (twins)

What is moscaicism?

1. During cleavage Mosaicism (a mitotic error) can happen. 2. Some of the cells of this individual will have 46 chromosomes and others 47 and create a mosaic-like form (when forming a blastocyst, the mosaic cell line does not become isolated and persists throughout the trophectoderm and inner cell mass. Mosaicism can be clinically relevant). 3. In many individuals it causes developmental problems.

PHASE 1: primordial germ cells (PGC) and their migration (form very early in an embryo). PHASE 2: increase in number of PGC by mitosis PHASE 3: reduction in chromosomal number (in the amount of DNA) by meiosis PHASE 4: structural and functional maturation of egg and sperm GAMETOGENESIS PHASE 1: primordial germ cells (PGC) and their migration

1. During its early life (2nd week), the embryo is bilaminar. 2. In the epiblast (one of the two layers), we can notice the appearance of primordial germ cells (PGCs). The germ cells form inside the Epiblast (intraembryonal). 3. In phase 1, the embryo has also developed an extraembryonal yolk sac (vitelline sac) outside, where PGCs migrate (from inside to outside) during the 3rd week of pregnancy in order to give the embryo time to develop. 4. PCGs migrate back to the internal embryo (they reach the gonads) around the 5th or 6th week (from inside to outside back to inside). While they move, PGCs proliferate (they proliferate mainly in the gonads, but also during their migration).

What is an extra stage in the formation of the notochord and what does it create for a short time?

1. During the development of the notochord, a communication is formed between the amniotic cavity and the yolk sac, which then is going to disappear. 2. While the notochord is elongating, the primitive streak is becoming shorter (this is one of the notochord's inductive properties).

What happens during the folding of the embryo to the yolk sac?

1. During the folding of the embryo, that takes place during the fourth week, part of the yolk sac is incorporated in the body of the embryo and becomes the primordial intestinal tube. 2. The region where the body wall of the embryo is not completed, so there is still a communication between the coelom and the extraembryonic coelom and the vitelline sac is still in communication just in the region with the primitive intestine (now in the body of the embryo) and this communication is called the vitelline duct/canal or omphalomesenteric duct/canal. 3. This communication is at the level of the midgut. This omphalomesenteric duct at some point will be incorporated in what will become the umbilical cord.

Why is meiosis "asynchronous"?

1. When looking at different segments of the seminiferous tubules, one will never see all spermatogonia at the same stages of maturation, hence the statement: adjoining segments of the seminiferous tubules present different stages of maturation of spermatozoa. 2. This is why meiosis is defined as 'asynchronous'; it doesn't start everywhere at the same time.

What do sclerotomes form?

1. Each sclerotome contributes to the formation of 2 vertebrae and, while the vertebral column is forming, the spinal cord starts to form inside the canal and starts making connections with the periphery through the future spinal nerves. 2. The notochord is going to regress and the only part that remains is the nucleus pulposus of intervertebral disks. Between two vertebrae, we can find the intervertebral disk which has the nucleus pulposus inside.

Fertilization Age vs. Menstrual Age to date a pregnancy:

1. FERTILIZATION AGE: This method is more precise but almost impossible to use. Indeed you should be able to know the exact moment in which the spermatozoa enters the egg, which is difficult because it can survive up to 4 days and the egg up to 2 days. With this calculation the pregnancy would last 38 weeks. Pregnancy is divided into the period of early embryo, period of embryonic organogenesis and fetal period. 2. MENSTRUAL AGE: This is the method commonly used in clinical evaluation; the counting starts on the onset of the last period. Since we can not be sure of the precise moment of the fertilization, we add 2 weeks of uncertainty: so the total is 40 weeks.

Passage through the Cervix is divided into 2 phases:

1. Fast Phase 2. Slow Phase

What are the 2 options for the corpus luteum after the 2 weeks after ovulation where the corpus luteum is functional?

1. Fertilization does not take place = corpus luteum becomes the menstrual corpus luteum. 2. Fertilization takes place = corpus luteum becomes the gravidic corpus luteum.

What are fetal complications caused by Polyhydramnios?

1. Fetal complications: defect of the CNS 2. Fetal death (risk is increased even when polyhydramnios is idiopathic) 3. fetal malposition 4. Premature rupture of membranes, sometimes followed by placental abruption 5. maternal respiratory compromise 6. Uterine atony (uterine wall is impaired because of the excessive pressure on it) ... (list goes on).

From the mechanical point of view, what drives folding in all these planes?

1. First, there is a differential growth of the different embryonic structures. 2. The embryonic disc (the embryo) and the amniotic sac (the amnion) grow very much. 3. On the other hand, the vitelline sac (the yolk sac) grows very little because we don't need the yolk sac to nourish the embryo. 4. So imagine that the amniotic sac grows so much that it occupies all of the chorionic cavity, all of the extraembryonic coelom. 5. The embryo is also growing - both thickening and elongating. In addition, structures that are on the midline of the embryonic disc, such as the developing notochord, neural tube, and somites (on the side of the neural tube) grow very much and make the central part of the embryo very stiff. 6. The folding therefore takes place on the lateral portion of the embryonic disc because the central part is very stiff. So most of the folding is concentrated in the thin, flexible outer rim of the disc, the periphery of the embryonic disc. 7. The cranial, caudal, and lateral margins of the disc fold completely under the dorsal axial structures and give rise to the ventral surface of the body. The dorsal axial structures - remember, the somites in the meanwhile are forming dorsal, the neural tube axial because they are on the axis of the body of the embryo. The rest of the embryo folds below these axial structures ventrally and in doing so, creates the body wall. The trilaminar disc forms a cylindrical embryo. Folding takes place on the median/sagittal plane. Those are called longitudinal folds: rostral or caudal. In response to a student question, the professor indicates that "no, they don't touch each other." On the horizontal/transverse plane, we have lateral folds. Folds come together ventrally in the region of the future umbilicus, where we have the entrance of the umbilical cord.

What is the placental membrane (barrier)?

1. Focusing on the exchange between capillaries in the villi and the blood in the lacunae. 2. There is no direct contact between the two, thanks to the placental membrane. The term membrane is more correct than barrier, since, as we will see, many substances pass through it. 3. It is a structure found between the fetal circulation, within the core of the villi and the lacunae with maternal blood. The following image will clarify its structure. 4. Within it we find the capillaries, some blue and some pink, showing the blood coming from the foetus with poorly oxygenated blood, full of wastes, and the other side full of oxygen and nutrients. 5. Initially the membrane is double-layered, made of syncytiotrophoblast and cytotrophoblast but later, as the pregnancy proceeds, around the 5th month, the cytotrophoblast disappears and there is only the syncytiotrophoblast. There are still some cytotrophoblast cells but they do not really contribute to the membrane anymore. 5th month disappearance of cytotrophoblast cells

Folding and formation of body cavities: What does folding of the embryo lead to?

1. Folding of the embryo leads to the formation of a "tube within a tube". 2. When the embryonic disk folds (imagine a piece of paper folding) we have the formation of a tube, which is the outer body wall. 3. But, during the folding of the embryo, there is another tube that also forms, which is the intestinal tube. 4. Part of the endoderm of the yolk sac is incorporated within the body of the embryo, forming the long intestinal tube. 5. This folding of the embryo and formation of a tube within a tube also leads to the delimitation of the intraembryonic coelom.

The two main hormones are:

1. Follicle-stimulating hormone (FSH) 2. Luteinising hormone (LH) ***Which are exactly the same hypophyseal hormones that will act on the female follicle.

While the vessels are still developing there must be something that flows into them:

1. For example there is the process of erythropoiesis taking place (formation of the corpuscolated part of blood and specifically of the erythrocytes). 2. At the beginning in the yolk sac we start to have the production of red blood cells, the placenta is also the site of erythropoiesis. 3. The AGM (aortic gonadal mesoderm) is a region around the aorta from which we have the formation of erythrocytes. 4. Then a big producer during fetal life is also the liver and reduces the production after birth until it disappears. 5. The spleen is responsible, too. At some point the production starts taking place in the bone marrow and will increase during the end of pregnancy and will continue all throughout life. 6. There are differences between fetal and adult hemoglobin, because of its affinity with oxygen.

During evolution of the animal body plan there are some major "key" events that can be noted:

1. first and foremost, formation of tissues (the 3 layers are the forerunners of the actual tissues) 2. second of all, symmetry, which in humans is bilateral but in other animals could be radial (but still a symmetry) 3. formation of body cavities 4. segmentation.

HATCHING OF THE BLASTOCYST AND EARLY IMPLANTATION: How does the blastocyst hatch and before implantation?

1. For the blastocyst to the implant, it has to hatch from the zona pellucida. 2. This happens because the microvilli from the trophoblast extend to the zona pellucida and they release proteases enzymes that digest the zona pellucida ( as it is formed by glycoproteins) and the embryo protrudes. 3. After 6-7 days the zona pellucida is shed and releases the blastocysts. 1) https://www.youtube.com/watch?v=XFRXWU1frNM 2) https://www.youtube.com/watch?v=7kC6p1twkXk

We talked about stages... What are the phases of human embryology?

1. Gametogenesis: production of gametes 2. Fertilisation: Process in sexual reproduction in which male and female reproductive cells join to form a new cell (zygote). 3. Cleavage: the cytoplasm of the mother is divided into a certain number of cells to form the embryos (more and more cells proliferate from the zygote). 4. Gastrulation: formation of the basic 3 layers from which all the tissues in the embryo develop. 5. Formation of the Body Plan (morphogenesis); at the beginning the body is a flat object (initial embryo), then it folds forming tubular structures (tubes-within-tubes); the embryo changes its shape over time becoming a complex curved object with rudimental organs. 6. Organogenesis: formation of the internal organs from the 3 embryological layers

In what oder does gastrulation occur and what does this mean?

1. Gastrulation takes place in a rostral to caudal manner, which means that during the 3rd week the rostro part of the embryo is at a more advanced stage than the caudal part. 2. Differentiation of the caudal region begins at the end of the 4th week (whatever happens in the 4th week is called Caudal dysplasia: Environmental factors and mutations). If something happens to the mother, it affects a different part of the body depending on what week it happens.

Causes of birth defects can be classified in three main categories:

1. Genetics chromosomal abnormalities (numeric, structural), mutation of genes. 2. Environmental factors drugs, viruses (eg. HIV), radiations (mother is exposed to radiation = affects the cells of the embryo), chemicals (eg. hormones; chemicals in water, food, soil). 3. Multifactorial inheritance genetic and environmental factors acting together (eg. maybe some are more susceptible to teratogens than others, etc.). For 50% to 60% of birth defect the cause is unknown.

Nuclear and cytoplasmic events, that together represent spermiogenesis, can also be summarized in 4 phases:

1. Golgi phase: mitochondria align in a spiral; the Golgi apparatus is condensed 2. "cap" phase: development of the axonemal complex and acrosomal cap 3. acrosome phase: formation of microtubules of the acrosome 4. maturation phase: we are able to distinguish mature spermatozoa composed of the head (with the acrosomal cap), neck (with the centriole), middle piece (with the spiral mitochondria), principal piece of the flagellum (tail), and end piece of the flagellum.

What is the SHH signal transduction pathway?

1. Hedgehog (Hh) is one of few signaling pathways that is frequently used during development for intercellular communication. 2. Hh is important for the organogenesis of almost all organs in mammals, as well as in regeneration and homeostasis. 3. Further, Hh signaling is disrupted in diverse types of cancer. 4. The vertebrate Hh signaling is not entirely dependent on an extremely specialized organelle, the primary cilium (PC), unlike other essential developmental signaling pathways. Several evidences demonstrate that embryogenesis and tumorigenesis have common characteristics, where both processes depend on coordinated mechanisms of proliferation, differentiation and migration. Vital signaling pathways for embryonic development and organogenesis are modulated in tumorigenesis. 5. Most activity of SH-signaling pathways take place at the level of the primary cilium.

One role (mentioned above) of sertoli cells is the secretion of other proteins. Explain the process of sertoli cells producing inhibin for feed-back loop to the hypothalamus:

1. Hypophysis is under the control of the hypothalamus, which produces some releasing and inhibiting factors which, for example, act on the adenohypophysis and control the production of adenohypophyseal hormones. 2. On the other hand, the hormones which are produced at the periphery, act through the feed-back loop both on the hypophysis and on the hypothalamus. 3. For example, Sertoli cells produce this inhibiting factor, an inhibitory loop, which goes back to the hypothalamus so that less hypothalamic-releasing factor is produced, stimulating the production of the follicle-stimulating hormone instead.

What happens if neural crests don't migrate properly?

1. If neural crests don't migrate properly all these structures are not formed properly (all the places seen in the image). A) All peripheral nervous system B) The medulla of the adrenal gland C) Part of the heart D) Bones in the skull E) Eye F) Melanocytes G) Teeth 2. To migrate correctly it is necessary that they go through an epithelial-mesenchymal transition and then when they reach the right spot go back again to a differentiated state through a mesenchymal-epithelial transition.

How is segmentation early on visible?

1. In a worm, segmentation is really evident and it is important in those early events since it allows motility. 2. However, there are regions of our body which show reminiscences of the process of segmentation. 3. One of them, very clearly visible, is the vertebral column made by vertebrae, segments of bones joined one to the other (each vertebrae originates from a specific somite). 4. This allows a good degree of flexibility to the trunk of the body (allowing us to bend and turn); the movements are limited by the fact that there are ligaments and muscles attached to them.

Why do annelids have a true coelomic cavity?

1. In annelids, the mesoderm is split into 2 sides. 2. One side remains on the side of the endoderm, and the other side remains on the side of the ectoderm. 3. The cavity in between is the coelomic cavity. 4. Many organs, especially at the beginning of the development, are suspended in the coelomic cavity by a dorsal and a ventral mesentery (these terms are also used for human embryos and adults, so get used to using them).

How do villi form (development of the villi)? Annotate this image: SOL

1. In light yellow we find the maternal endometrium, in purple we find the syncytiotrophoblast, in green the cytotrophoblast and in brown the mesoderm. 2. The cytotrophoblast starts to proliferate forming the primary villi. Then, the mesoderm begins to colonize the inside of the primary villi. 3. Now that there is a core of mesoderm inside the villus we can define the secondary villi. 4. Then in the mesoderm of the secondary villi we start to have the formation of a capillary network, that will be connected with the umbilical vessels on the side of the embryo. That is called a tertiary villus.

PHASE 1: primordial germ cells (PGC) and their migration (form very early in an embryo). PHASE 2: increase in number of PGC by mitosis PHASE 3: reduction in chromosomal number (in the amount of DNA) by meiosis PHASE 4: structural and functional maturation of egg and sperm PHASE 2: increase in number of PGC by mitosis in MALES (because the following phases of gametogenesis have a different pacing in male and female).

1. In males PGCs are located in the seminiferous tubules. They are named spermatogonia and they are dormant until puberty (there are very few spermatogonia compared to oogonia). 2. Only few of them proliferate before puberty and, anyways, not after the 6th week. Proliferation of PGCs during the early embryonic period. 3. They dormant (sleep) very early = from the 6th week until puberty. 4. Intensive proliferation after puberty throughout life. After puberty and throughout life spermatogonia intensively proliferate. Males are fertile also at an old age, whereas women are not. *** Males are fertile also at an old age ≠ from females

In what animals, and why, is the allantois important?

1. In other animals - for example, birds - the allantois is important as an exchange organ. 2. The yolk sac is important for nourishment, as we saw in the large yolk sac of that bird that was developing. 3. The allantois is important for exchanges with the external environment through the eggshell.

What do all the components produced by the follicle trigger at ovulation?

1. In ovulation, all things produced by the follicle that are close to the surface of the ovary trigger an inflammatory reaction and the blood flow starts to be reduced. 2. Stigma is the region where before ovulation blood flow stops at the ovarian surface just above the mature Graafian follicle. 3. These are the conditions to break the surface of the ovary. 4. At ovulation (more or less 38 hours after LH and FSH surge) this inflammatory reaction ruptures the outer wall of the follicle and the surface of the ovary breaks. What slides out the surface of the ovary is called the ovulated complex.

In summary, what is the formation of the tail fold due to?

1. In summary, the formation of the tail fold is due to the growth of the distal part of the neural tube. 2. It grows so much that it projects over the cloacal membrane, so everything bends. It results in the formation of a posterior endodermal pocket - the hindgut. 3. The connective stalk is now located ventral to the body of the embryo. 4. It is important to remember the connecting stalk because that is the forerunner of the umbilical cord. 5. The connective stalk is now attached to the ventral surface of the embryo and it has incorporated a portion of the yolk sac, the allantois. 6. The primitive streak is now caudal to the cloacal membrane because everything is inverted like in the rostral region.

What do ectopic pregnancies cause?

1. In the large majority of cases it takes place in the uterine tube and gives rise to uterine tube rupture and haemorrhage and could cause the death of both mother and embryo. 2. It may present itself with abnormal uterine and vaginal bleeding, pelvic and abdominal pain and a massive first trimester bleeding. 3. It can be disguised with appendicitis or with aborting intrauterine pregnancy. In these cases the diagnosis depends on the type of person who is experiencing the symptoms: as if a 60 year old woman feels this array of symptoms it is unlikely to be an ectopic pregnancy. 4. Ectopic pregnancy produces 𝝱 human chronic gonadotropin at a slower rate causing a possible false negative pregnancy test.

IN THE MEANWHILE.. What happens meanwhile the blastocyst hatches and before it implants?

1. In the meanwhile, there is a preparation of the uterine mucosa for implantation at the end of the menstrual cycle. It has to create a suitable cellular and nutritional environment and has to form an immune-privileged site for the embryo to not be recognized as a foreign body. 2. The endometrium forms the decidua which is a modified mucosal lining of the uterus in preparation for the implantation. 3. Every month the mucosa undergoes this process, that will be useful only when fertilized, otherwise, it regresses.

PHASE 1: primordial germ cells (PGC) and their migration (form very early in an embryo). PHASE 2: increase in number of PGC by mitosis PHASE 3: reduction in chromosomal number (in the amount of DNA) by meiosis PHASE 4: structural and functional maturation of egg and sperm PHASE 2: increase in number of PGC by mitosis in FEMALES (because the following phases of gametogenesis have a different pacing in male and female).

1. In the ovary, PGCs are invested by support cells and become oogonia (they are 7 million and go down to 400 ovulated). 2. by the 5th month they have all entered the prophase of the first meiotic (of meiosis 1) = that is when they are called primary oocytes (surrounded by the somatic cells), which are then called primordial follicle (when they are associated with the somatic cells that surround them). 3. Meiosis I is completed at ovulation and meiosis II starts immediately after. If the oocyte is not fertilized, it will never complete meiosis II.

How does egg/zygote transport work? (2)

1. Initially the transport is slow, especially when the egg moves through the ampulla (enlargement after the infundibulum); this segment of the tube is the widest and is the area in which fertilization is most likely to take place. 2. This slow transport in the ampulla can last around 3 days (72 h), and is slowed down by the many folds of the mucosa, allowing ample time for possible fertilization. 3. After this slow period the transportation is much faster, the egg moves from the isthmus (the segment after the ampulla) to the uterine cavity in just 8 hours.

UMBILICAL CORD: PLACENTAL ATTACHMENT

1. On one side the umbilical cord enters the body of the embryo while on the other side it is attached to the fetal side of the placenta. Usually it attaches near its center (eccentric attachment) but it may also attach more peripherally (marginal attachment). It doesn't always attach in the right place. 2. NB: we can preserve the umbilical cord because it contains some foetal stem cells. They can be used for studies, or can replace for example hematopoietic stem cells (e.g. leukemia: you need to destroy the cells of the bone marrow and replace them with stem cells)

What happens during the stage of the late primary follicle?

1. Inside the oocyte there are cellular changes taking place, one of them is inside the oocyte cytoplasm where there starts to be production of granules, called cortical granules. 2. These position themselves just below the plasma membrane of the oocyte (oolemma). 3. The cortical granules have to remember when spermatozoa enter the oocyte. 4. Another thing that happens is that there is a tiny space that forms between the oolemma and the zona pellucida, called the perivitelline space. 5. Many spermatozoa manage to cross zona pellucida, reach the perivitelline space but when one of them comes into contact with the oolemma hundreds of spermatozoa get trapped in perivitelline space and die. 6. This type of follicle can be called the late primary follicle.

Later, in the trunk, we have the formation of two types of paraxial mesoderm:

1. Intermediate mesoderm 2. Lateral plate mesoderm.

If no fertilization takes place, the corpus luteum becomes...

1. It becomes the Menstrual Corpus Luteum. 2. The corpus luteum needs to degrade in order to make space in the ovary for new forming follicles and so there is regression: the hormone production declines and stops after 10 days, and vascularization decreases. 3. The corpus luteum becomes the corpus albicans; white in colour due to decreased vascularization and then becomes scar tissue. 4. In older women who have been fertile for quite some time, more scar tissue is seen on the surface of the ovary.

How can a placenta abruption be caused?

1. It can be caused by traumas, smoking, hypertension, preeclampsia (edema, proteinuria, hypertension), use of drugs. 2. Basically, it can be caused by whatever causes an increase of pressure in the blood vessels that supply the placenta. It can lead to painful bleeding in the third trimester, possible DIC (diffuse intravascular coagulation), maternal shock, fetal distress, and life threatening, if the mother bleeds to death. Also, the fetus can suffer because of reduced blood supply. 3. Bleeding can be internal and therefore concealed. This is one of the worst situations, because you don't always notice that something is wrong. In the ultrasound you can see a detachment of the placenta (shown by the arrow) and an internal bleeding.

Let's describe this image:

1. Low implantation is close to the neck of the uterus and it can cause little bleeding. 2. Partial placenta previa is when only part of the opening of the neck of the uterus is covered by the placenta. 3. Total placenta previa (the one we were talking about before)

What happens with the activation of MPF?

1. Meiosis I completed 2. Meiosis II begins and is arrested in metaphase 3. Formation of the secondary oocyte. There is also the formation of the first polar body (in the perivitelline space -- cytoplasm just for one cell).

Meiosis is

1. Meiosis is the reduction in the number of chromosomes 2. Reassortment of paternal and maternal chromosomes 3. Further redistribution of paternal and maternal genetic information during the crossing over of the first meiotic division -- so we ensure that we have all the genetic material (DNA).

Passage through the uterus

1. Most of the spermatozoa that made it to the uterus will now move towards the uterine tube with the ovulated oocyte but a good portion go towards the wrong fallopian tube. 2. Whilst moving through the uterus, many spermatozoa will be captured and phagocytosed by the cells of the immune system and die, so only several hundred will reach the tube containing the oocyte. 3. They reach the isthmus (narrow part) of the uterine tube and bind to the mucosa, for around 24h, and this is important because this allows for the capacitation reaction to take place. 4. Capacitation is the process where the components that were added to the sperm in the epididymis are now removed: some cholesterol from the plasma membrane of the sperm head and some glycoproteins from the membrane component.

Characteristics of late primary follicles:

1. Now the follicular cells are not monolayered as before, they do not have a single layer, they are cuboidal but are several layers of follicular cells that surround the oocyte and the zona pellucida. 2. These follicular cells, which can reach 10-12 layers as the follicle is growing, are now called the granulosa cells. 3. Oocytes are surrounded by granulosa cells, which are starting to express receptors for the follicle stimulating hormone (FSH). 4. Moreover, this multilayer lies on a membrane that is called the membrana granulosa, which is important because it is a barrier to capillaries from the stroma that cannot enter between follicular cells, while nutrients and fluids can pass from capillaries to granulosa cells for the maturation of the follicle.

Compare male and female gametogenesis and summarize their differences

1. On the other hand, the egg provides the other half of the DNA, but also organelles, building blocks for compounds such as proteins and nucleic acids, and other necessary materials. 2. The egg, being much larger than a sperm cell, contains almost all of the cytoplasm a developing embryo will have during its first few days of life. 3. Therefore, oogenesis is a much more complicated process than spermatogenesis. 4. Oogenesis begins before birth and is not completed until after fertilization. 5. Oogenesis begins when oogonia (singular, oogonium), which are the immature eggs that form in the ovaries before birth and have the diploid number of chromosomes, undergo mitosis to form primary oocytes, also with the diploid number. 6. Oogenesis proceeds as a primary oocyte undergoes the first cell division of meiosis to form secondary oocytes with the haploid number of chromosomes. 7. A secondary oocyte only undergoes the second meiotic cell division to form a haploid ovum if it is fertilized by a sperm. 8. The one egg cell that results from meiosis contains most of the cytoplasm, nutrients, and organelles. 9. This unequal distribution of materials produces one large cell, and one cell with little more than DNA. 10. This other cell, known as a polar body, eventually breaks down. 11. The larger cell undergoes meiosis II, once again producing a large cell and a polar body. 12. The large cell develops into the mature gamete. 13. The unequal distribution of the cytoplasm during oogenesis is necessary as the zygote that results from fertilization receives all of its cytoplasm from the egg. So the egg needs to have as much cytoplasm as possible.

What about other factors?

1. On the other hand, there are some other factors, such as Wnts and Bmps, that are more concentrated laterally. We basically have two opposite gradients of different factors. 2. The expression of these factors determines the organization of the mesoderm according to a pattern that goes from medial to lateral.

Completion of meiosis II and development of pronuclei: formation of the zygote:

1. Once the processes of replication have taken place within the two pronuclei (they are referred to as pro-nuclei because they are the forerunners to a single, combined nucleus) and have fused together into a single nucleus, this structure can be referred to as the zygote. 2. Whilst the two genetic materials are separate it cannot be referred to as a zygote/embryo, it is only from the point of fusion into a single nucleus where the genetic material mixes and mingles, that this new structure can be considered a new being/organism. 3. The zygote is a large cell and at this point is now ready for cleavage, the process in which the cell will no longer be unicellular.

What is situs inversus totalis?

1. One example of things that can go wrong during the initial development of the third week is the situs inversus totalis. 2. In fact, this condition causes everything inside our body to be positioned mirror-like. It is usually not clinically relevant. 3. If the dynein in the cilium is mutated, meaning left-to-right rather than right-to-left, the bending of the cilia it's going to be to the right as well, hence all the factors mentioned before will go to the right obtaining the so called situs inversus totalis. 4. Situs inversus can be associated with problems in other regions of the body where there are motile cilia, such as in the Kartagener Syndrome condition. 5. In this case, more than a problem in the bending of the cilia there's a problem with the motility of the cilia. This anomaly can cause infertility because the flagellum of the spermatozoa doesn't work properly (flagellum is like a bigger cilium); the patient can also suffer from pathologies of the respiratory tract because of the mucus ciliary escalator that moves the mucus towards the pharynx (if the mucus cannot be moved we get inflammation and infections).

When looking at the very simple animal like the worm, how is the mesoderm divided?

1. One layer remains in the side of the future intestine, which is the visceral layer, or splanchnopleure, whilst the other side remains in the side of the ectoderm, which is the parietal layer, and the future somatopleure in humans.

What are the different subdivisions of the mesoderm? 1. Prechordal plate: a meso-endodermal structure = important for the development of the head and of the rostral part of the nervous system 2. Notochord: what remains in the adult is just the nucleus pulposus in between the vertebrae, but during development it's very important for the formation of part of the nervous system 3. Paraxial mesoderm: it's divided into somites and is important for the formation of the vertebral bodies 4. Intermediate mesoderm: formation of the gonads, kidneys, urinary tract and initial part of genital tract 5. Lateral plate mesoderm: important for the formation of the intraembryonic coelom, so the body cavities; it's in continuity with the extraembryonic mesoderm 6. Extraembryonic mesoderm: surrounds amniotic cavity and yolk sac 7. Primitive heart field: forms within a specific region of the lateral plate mesoderm

1. One of the domains of the mesoderm is the forerunner of the heart. 2. During the migration of the mesoderm, some cells that migrate in the primitive streak they position themselves in the splanchnic mesoderm and form the primary heart field or cardiac crescent. 3. Cells when they are migrating, they already know their final destination, meaning that they know if they are going to become part of the atrium, of the ventricle or of the aorta of the heart.

Such cavities can provide numerous functional advantages. Advantages of having an intraembryonic coelomatic cavity:

1. Organs that form and develop inside the coelom (cavity lined by a smooth serosa with a layer of fluid), can move freely, grow and develop. If an organ forms inside the solid cavity (a cavity filled with mesoderm), the organ cannot grow very much, and cannot really move around much. This free movement within serosal cavities allows organs of the digestive tract to develop independently of the body wall, while the fluid inside also helps protect them from any shock. 2. Peristalsis of the gut does not affect the body wall. This is a good thing. When you eat and the food moves along your digestive tract, you do not physically see your body wall moving. 3. Movements of the body wall during locomotion do not distort internal organs. This is another very important thing because when organs develop inside the serosal cavity, the somatic movement of the body (from running or jumping) does not distort and affect the organs within the serosal cavities. 4. Organs can be attached to one another so that they can be suspended in a particular order while still being able to move freely within the cavity. Many organs of the digestive tract are surrounded by a serosa and are suspended by serosal ligaments and attached to one another. This means that they can be displaced in the abdominal cavity without losing their reciprocal relationship. Imagine a female of our species that is pregnant. At some point, the uterus will start to become bigger and bigger, as the fetus' size increases, so the organs of the abdominal cavity need to be able to push themselves aside so we can make space for the growing uterus. Once the baby is delivered, the organs will move back to their original position (this also explains the next point). This smooth serosal layer and ligaments are also what allows abdominal surgeons to remove organs and move them around during surgery. 5. Space for growth of new members of the species inside the maternal body (explained with the example above). 6. Formation of an efficient circulatory system due to all the space inside.

What is the period of hyperactivity?

1. Period of hyperactivity: Once capacitation is completed the sperm become incredibly motile and enter a "frenzy", able now to free themselves from the isthmus where they were attached and proceed to the ovulated complex. 2. They move counter-currently from the movement of the cilia and the uterine tube contraction, which is trying to move the oocyte to the uterus; the sperm must therefore swim very hard towards the ampulla, as this is the area where it is most likely to find the oocyte.

What are the phases of fertilization?

1. Phase 1: Penetration of the Corona Radiata 2. Phase 2: Attachment and Penetration of the Zona Pellucida. 3. Phase 3: Binding to the Oocyte Membrane and Fusion of the spermatozoon and Egg. 4. Phase 4: Prevention of Polyspermy 5. Phase 5: Formation of Male and Female Pronuclei

What is Pitx-2?

1. Pitx-2 is an homeobox, which are an evolutionary conserved class of transcription factors that are key regulators during developmental processes such as regional specification, patterning and differentiation. 2. It contains transcription factors that are going to promote the transcription of specific sequences of DNA downstream later on in the process. 3. As previously mentioned, they are evolutionary conserved genes, which means that they are overall very important to contribute to the general arrangement of the body (to the placement and positioning of different structures). 4. These genes code for highly conserved DNA-binding domain proteins, called homeodomain, which bind to other sequences of genes and therefore promote their transcription. Homeobox genes play a crucial role in specifying cell identity and positioning during embryonic development and mutations in these genes can cause dramatic developmental defects.

For example, in this drawing we can see many of these cases. Pathological Placenta (cases):

1. Placenta accreta 2. Placenta increta 3. Placenta percreta 4. Placenta previa

What are the different subdivisions of the mesoderm? The different pathways of migration give rise to:

1. Prechordal plate: a meso-endodermal structure = important for the development of the head and of the rostral part of the nervous system 2. Notochord: what remains in the adult is just the nucleus pulposus in between the vertebrae, but during development it's very important for the formation of part of the nervous system 3. Paraxial mesoderm: it's divided into somites and is important for the formation of the vertebral bodies 4. Intermediate mesoderm: formation of the gonads, kidneys, urinary tract and initial part of genital tract 5. Lateral plate mesoderm: important for the formation of the intraembryonic coelom, so the body cavities; it's in continuity with the extraembryonic mesoderm 6. Extraembryonic mesoderm: surrounds amniotic cavity and yolk sac 7. Primitive heart field: forms within a specific region of the lateral plate mesoderm

Recap questions: How can we classify follicles?

1. Primordial A) Primary oocyte B) one layer of follicular cells -squamous epithelial cells than are rather flat C) Formed during the 5th month D) No zona pellucida at this point 2. Primary A) Follicular cells are now cuboidal and multilayered, forming the granulosa B) Zona pellucida 3. Secondary A) Theca (stroma surrounding the granulosa)is formed B) Theca externa -connective tissue responsible for protection C) Theca interna -responsible for vascularization of the oocyte, produces hormones needed for oocyte maturation and preparation of female genital tract for possible pregnancy

What are problems during meiosis?

1. Problems during meiosis may occur. 2. Diseases such as Down syndrome are the consequence of anomalies in meiosis. 3. This syndrome is a case of trisomy: 3 chromosomes instead of 2 (consequence of a non-disjunction during meiosis II).

What is progeria?

1. Progeria is a disease resulting in rapid aging. 2. The baby becomes older very quickly and dies at 13-15 years as an old individual. 3. It is caused by the mutation of a gene which codifies a protein that is part of the nuclear lamina (gene LMNA). 4. We all have that protein, but only few people are affected by this serious disease (around 250 cases globally).

PHASE 1: primordial germ cells (PGC) and their migration (form very early in an embryo). PHASE 2: increase in number of PGC by mitosis PHASE 3: reduction in chromosomal number (in the amount of DNA) by meiosis PHASE 4: structural and functional maturation of egg and sperm

1. Reduction in the number of chromosomes 2. Reassortment of paternal and maternal chromosomes 3. Further redistribution of paternal and maternal genetic information during the crossing over of the first meiotic division 4. So mitosis and meiosis have different pacing for male and female gonocytes. 5. Formation of viable gametes: 4 in males, 1 in females -- the other 3 will eventually die, because there's only 1 viable female gamete.

How does the folding in the region of the heart tubes occur?

1. Remember that in the rostral region of the embryo there were 2 endocardial tubes. 2. When the embryo folds laterally, the two tubes come close to one another on the midline. 3. Because of the lateral folding of the embryo, the region where the endocardial tubes are formed results in them coming together and fusing to form a singular tubular heart.

Recap questions: Why do we care about the granulosa/layers of follicles?

1. Responsible got the conversion of testosterone to oestrogen 2. Hormone production which is necessary to prepare the female reproductive tract for possible pregnancy.

What is the importance of calcium in the fourth phase of fertilization?

1. Resumption of meiosis II (as the oocyte was arrested in the initial phase of meiosis II). 2. Formation of the pronuclei (now 2 nuclei in the cell = one from the spermatozoa and one from the oocyte). -- now we have 46 chromosomes (23 + 23) -- now have to fuse these to form a diploid -- leads to phase 5 of fertilization.

The ovulated complex consists of:

1. Secondary oocyte (ovum) 2. zona pellucida 3. Corona radiata (cells of granulosa which have remained attached to zona pellucida). 4. Sticky material from the matrix that corresponds to hyaluronic acid and to fluid in the antrum

Summarize the hormonal regulation of spermatogenesis:

1. Sertoli cells respond to FSH (hypophysis) and to testosterone (Leydig cells). 2. Sertoli cells receive the input by FSH but also respond to androgens. 3. FSH-stimulated Sertoli cells produce androgen-binding protein which binds testosterone and the complex (androgen-binding protein + testosterone) is carried into the fluid compartment of the seminiferous tubule (the lumen presents a high concentration of androgen) where it exert a strong effect on spermatogenesis. 4. The maturation process starts in the basal compartment, proceeds in the abluminal compartment, and results in the presence of more mature spermatozoa in the lumen. Sertoli cells transform some testosterone into oestrogens. 5. Even though we are talking about the male gonad, this process does not only rely on male hormones but also requires oestrogens. Some estrogens are carried back in a paracrine fashion to Leydig cells (in the stroma) together with a stimulating factor. *** Paracrine means the effect is local Inhibin produced by Sertoli cells inhibits FSH secretion. *** Goes back to the hypothalamus and then to the adenohypophysis to reduce the amount of FSH production, making it a system that controls itself.

What are possible issues while becoming trilaminar (= during the 3rd week)?

1. Sirenomelia 2. Conjoined Twins 3. Situs Inversus

What are anomalies that can occur in this ciliary movement and what may they cause?

1. Situs Inversus Totalis; Mutation in the Lrd gene in mouse iv/iv, which leads to the Kartagener Syndrome; Situs inversus plus immotile respirtory cilia and sperm flagella Mutations in dynein genes and deficiency in ciliary dynein arms

So overall, what is there a high concentration of?

1. So overall, there is a high concentration of these two second messengers (cAMP and cGMP) in the cytoplasm of the oocyte so that the oocyte is arrested in meiosis I. 2. Before ovulation all this system changes, cyclic AMP is transformed into 5'AMP and cGMP doesn't flow any longer from follicular cells inside the cytoplasm of the oocyte.

Folding on the horizontal plane or formation of lateral folds in the embryo:

1. So, the amniotic sac is growing very much = growing so much that it starts to slide on the side of the embryo, on the right and left sides. 2. This causes the periphery of the embryonic disc to bend and start to incorporate into the body of the embryo part of the endoderm that lines the yolk sac. 3. The formation of the gut tube (shown in yellow) results when the yolk sac endoderm continues to be incorporated into the body of the embryo until a long tube is obtained, which is called the intestinal tube. 4. Now looking at the destiny of the intraembryonic coelom = On the image (in orange), you find the lateral plate is divided into a splanchnopleure and a somatopleure. 5. While the amniotic sac slides on the side of the embryo, the intraembryonic coelomic cavity is carried ventrally to the body of the embryo as well and starts to surround the intestinal tube. When you compare images (b) and (c), you can see that while part of the yolk sac is incorporated into the body of the embryo, the intraembryonic coelom is moving ventrally to the side of the intestinal tube. 6. At this point, the splanchnic mesoderm (the ventral-most layer of the lateral plate mesoderm) surrounds the endoderm of the gut tube, while the somatic mesoderm (what we call somatopleure) is on the other side - the side of the future body wall. 7. The cavity in between them is still the intraembryonic coelomic cavity. Before it was lateral (on the side), but now because the most lateral aspect of it folds ventrally, the intraembryonic coelomic cavity comes to lie on the side of the future intestinal tube. So the splanchnopleure remains on the side of the wall of the future intestinal tube, while the somatopleure remains on the side of the future body wall. 8. Between them is the intraembryonic coelomic cavity which is lined by a mesothelium that is developing in the meanwhile, meaning its serosa. The intraembryonic coelom that surrounds the intestinal tube has become a serosa cavity that will be divided into a rostral part, a middle part, and a caudal part. The layer of the serosa which is on the side of the intestine is called the visceral layer of the serosa, while the layer of serosa that remains on the side of the body wall is called the parietal layer of the serosa.

Recap:

1. So, the chorionic cavity grows so much that the wall of the chorionic cavity on the side where there is not the embryo (leave) it comes into contact with the amniotic membrane and, at that level, there's the formation of the amniochorionic membrane. 2. This membrane will then fuse with the wall of the uterus where there is the decidua parietalis. At the level of the neck of the uterus, at the end of the pregnancy, this amniochorionic membrane breaks. Consequently, the amniotic fluid comes out of the vagina and the uterine tube and there's the famous "breaking of the waters" or "losing of the waters".

What is cavitation?

1. Some cavities start to form within the mesenchyme of the lateral plate mesoderm, leading to the formation of a cavity, which is the intraembryonic coelom (look at the diagrams on the top of the picture beside, which show a cross-section of the embryo). 2. The dorsal layer is the one that will be in continuity with the extraembryonic mesoderm that covers the amniotic sac. 3. that covers the amniotic sac. The extraembryonic mesoderm is the mesoderm that is formed by the primitive endoderm and positions itself between the cytotrophoblast and the wall of the vitelline sac. It grows so much that it goes over the amniotic sac. 4. At that point, we saw that within the extraembryonic mesoderm, there was a process of cavitation that would lead to the formation of the extraembryonic coelom or the chorionic cavity. 5. The lateral plate mesoderm which is at the boundaries of the embryonic disk is in continuity with the extraembryonic mesoderm, which covers the amniotic sac from above, and the yolk sac ventrally. The dorsal layer of the intraembryonic mesoderm of the lateral plate which is in continuity with the extraembryonic mesoderm that covers the amniotic sac is called the somatopleure (parietal layer). The ventral one, the one in continuity with the extraembryonic mesoderm that covers the yolk sac is called the splanchnopleure (visceral layer). 6. In the central/caudal region of the embryo, this intraembryonic coelomic cavity is in communication with the extraembryonic coelomic cavity. At some point, that communication will be closed, but it needs to be present for a few weeks. We will understand why when we will study the development of the intestinal tube.

If we observe the embryo macroscopically during the fourth week we can define 2 major events:

1. folding, which leads to the formation of body cavities in which organs are placed. 2. segmentation, a process that is going to be very important for the overall organization of the adult body.

What is the secondary follicle?

1. Some growing follicles degenerate and some enlarge by taking up fluids. 2. This is the secondary follicle (also called the antral follicle) in which the oocyte has become bigger (125 micrometers) and there are some cavities filled with hyaluronic acid and watery fluid forming in between the granulosa cells. 3. At some point these small cavities coalesce to form a large cavity that is called the antrum, now the follicle is an antral follicle (pre Graafian follicle).

Passage through the Cervix is divided into 2 phases: What is the fast phase?

1. Some sperm pass very quickly through the neck of the uterus to the uterine tube (fallopian tube). 2. These sperm reach the fallopian tube, and potentially the oocyte, within 5-20 minutes from the moment of ejaculation. 3. They are motile but are, however, less likely to fertilize the egg as they have spent too little time in the female reproductive tract and therefore have not been capacitated. 4. This phase is mostly due to the contraction of the uterus during ovulation as a biological mechanism to propel sperm towards the oocyte; but the mechanical propulsion of ejacualtion and high motility of these few spermatozoa also contribute to the fast movement.

What else happens when the oocyte undergoes folliculogenesis?

1. Something that can be observed is that the oocyte has become larger and is growing, accumulating things that might be useful. 2. The oocyte increases its diameter, the follicular cells from flat become cuboidal cells, in between the plasma membrane of oocyte (oolemma) and the apical domain of follicular cells we have deposition of a membrane called zona pellucida.

What are amniotic bands?

1. Sometimes the amniotic membrane (lining, wall of the amniotic sac) start to detach in places, some pieces start to float in the sac (delamination) and wrap themselves around portions of the body of the fetus (i.e. fingers, legs, neck). 2. Then the fetus starts to grow and there is a constriction. 3. Therefore the distal part towards that constriction cannot grow as it should up to the point of being amputated. ***Children with the upper part of their fingers amputated are typically associated with complications of the amniotic band.

What will happen after the formation of the epiblast?

1. Soon after the formation of the epiblast, within the cells of this layer a cavity forms: it's the initial amniotic cavity (C in image) that will give rise to the amniotic sac (which is formed in the epiblast), which will surround the embryo. 2. At the beginning, the amniotic cavity is open, so there's no roof, but soon the amniotic membrane (lighter blue in image E-F) will form and close it. → With respect to the embryonic disc, the amniotic cavity is dorsal. 3. While the amniotic cavity is forming, another structure called parietal endoderm or Heuser's membrane develops. 4. → (B-C) Some cells from the primitive endoderm or hypoblast start to proliferate as to line from the inside the cytotrophoblast: this layer is called the parietal endoderm or Heuser's membrane. 5. → (D) Another category of cells originate from the parietal endoderm and position themselves between the parietal endoderm and the cytotrophoblast, taking the name of extraembryonic mesoderm. They're a differentiation of the yellow cells. 6. → (E-F) The amount of red cells increases and finally we have a layer of mesodermal cells in between the parietal mesoderm and the cytotrophoblast, but also in between the amniotic membrane and the cytotrophoblast. The extraembryonic mesoderm supports epithelium of the amnion and yolk sac and of the future chorionic villi (forerunners of the placenta). It's also the precursor of the future blood vessels. 7. → (E) The space that is now delimited by the parietal endoderm is the primary yolk sac or vitelline sac 8. → During the development of humans it's not such a relevant structure because the nourishment of the embryo arrives through the placenta. → At this point there's no circulation yet but just diffusion from lacunae filled with maternal blood. → For all those organisms that develop outside the maternal environment with no connection with it, the yolk sac is rich in a lot of nutrients important to sustain development until completion 9. → (F) There is another wave of proliferation of extraembryonic mesodermal cells that constrict at some point the primary yolk sac forming the definitive yolk sac that is much smaller. What remains of the previous sac due to this constriction is called the remnants of the primitive yolk sac. → the secondary yolk sac is ventral to the epiblast.

Where does spermatogenesis begin?

1. Spermatogenesis begins in the hypothalamus, which secretes gonadotropin-releasing hormone (GnRH). GnRH targets the anterior pituitary gland, which then secretes luteinizing hormone (LH) and follicle-stimulating hormone (FSH). 2. These two hormones target the testis, with LH targeting the interstitial cells and FSH targets androgen-binding receptors 3. They increase testosterone secretion; which increases spermatogenesis. 4. Enhancing testosterone secretion and receptors. 5. Inhibin is secreted. Blocking the hypothalamus from starting spermatogenesis.

Why is the zona pellucida important?

1. Stops other sperm from penetrating the egg. 2. Hence it is important for the destiny of spermatozoa that reach the oocyte as well as for the initial development of the embryo. 3. The oocyte and the follicular cells keep on communicating across the zona pellucida. -- For example, microvilli of follicular cells extend to the zona pellucida and through the gap junction they communicate again with the oocyte, otherwise it would not keep the oocyte with the right amount of secreting second messengers.

MEIOSIS in males

1. Surge of testosterone at puberty and it leads to the development of secondary sex characteristics. -- the appearance of the male gonad changes dramatically. Before puberty, there was just this bunch of PGC. 2. Hence, at puberty, there is a (a) maturation of somatic cells (Sertoli cells) into seminiferous tubules (b) Proliferation of PGCs and formation of spermatogonia (c) Secondary sex characteristics 3. Testosterone starts to flow in the blood circle and to form some canicola, where spermatogonia will differentiate and proliferate. It makes somatic cells (Sertoli cells) maturate into seminiferous tubules. At this moment, PGCs proliferate and form spermatogonia. Then, spermatogonia start to mature, entering meiosis. 4. The process is asynchronous: depending on the place where the spermatogonia are, they mature and differentiate in spermatozoa sooner or later. 5. Meiosis I is completed in 24 days. Spermatogonia immediately enter meiosis II, which takes 8 hours to be completed. Spermiogenesis lasts 24 days. 48 days pass from the proliferation of PGCs to spermiogenesis. (Unlike females, where the process of meiosis is synchronous -- by the 5th month of fetal gestation all oogonia begin meiosis).

Why do we have to study the formation of the intraembryonic coelom? Why is it important to have an intraembryonic coelom?

1. The acquisition of an intraembryonic cavity that will be smoothly lined by a mesothelium and filled with a fluid is an important evolutionary step; evolutionarily speaking, it is very important to have an intraembryonic coelom and to have cavities lined by a serosa. 2. The acquisition of an intraembryonic cavity that will be smoothly lined by the mesothelium (a special type of epithelium with flat epithelial cells; characteristic of the serosae) and that can be covered with fluid is an important evolutionary step. 3. These coelomic cavities are cavities that are somewhere between the body wall and the gut in most animals.

What is the allantois?

1. The allantois in humans is the vestige of urinary and respiratory organs. In birds and reptiles, that need a bigger and 'plentier' vitelline sac, the presence of this allantois is essential. In humans is very small compared to theirs and is basically a diverticulum, an evagination, of the endoderm of the yolk sac into the body stalk. 2. In humans, in the mesoderm of the body stalk, around the allantois, we have the formation of blood vessels. These blood vessel will form the umbilical circulatory arch: arteries and veins (2 up to a certain point) will connect the placenta with the embryo. This allantois and the body stalk in which it has been extruded will form the umbilical cord: because of the folding of the embryo the body stalk will get close to the vitelline sac, then come together and form the umbilical cord. 3. Talking about the development of the urinary system and the urinary tract the allantois will form a ligament (become very soon atrophic-connective tissue, also because it will lose the connection with the vitelline sac) and then form the ligamentous device that is called the urachus in our fetal life. In the adult this ligament will be attached to the urinary bladder and it will become the median umbilical ligament. → we need to remember the allantois because is inside the body stalk, around it we have the formation of the umbilical vessels and then at some point it will form a ligamentous device (urachus) that in the end will become one of the ligaments of the urinary bladder. 4. This is us, mammals and in yellow there is the yolk sac and in green there is the allantois. The difference in size can be noticed between mammals and reptiles/birds. Yolk sac and allantois are really important for them, but not really for humans.

What happens to the amniotic sac?

1. The amniotic sac grows so much that it slides on the side of the embryonic disc and is a major mechanical determinant of the folding of the embryo. 2. In the 3 weeks of the image, the blue cavity is the amniotic cavity. 3. At 3 ½ weeks, the amniotic sac is growing and contributing to the bending of the embryo. 4. At 4 ½ weeks, both the embryo and the amniotic sac have been growing - which decreases the space in the extraembryonic coelom. 5. At 2 months, we talk about the fetus, not the embryo. The amniotic sac has completely filled the extraembryonic coelom (the chorionic cavity).

What happens at the level of the primitive node?

1. The best established model of what happens at the level of the primitive node because of the movement of the cilia states that, because of the bending of the cilia, a lot of morphogens, molecules packaged together as SHH, retinoic acid are swept to the left. 2. Clearly, a consequence of this sweeping is that the molecular patterning of the left becomes different from the one on the right. 3. Some ciliary currents are generated and among the factors which are swept to the left we can find retinoic acid, which is a differentiating factor, sonic hedgehog and the fibroblast growth factor-8. 4. Once again, because of this movement something happens only on the left side of the embryo such as the expression of the transcription factor nodal which activates Pitx-2.

What is the body stalk attached to?

1. The body stalk is initially attached to the caudal end of the embryonic disc, before folding. 2. After caudal folding it becomes ventral to the body of the embryo, attached to the ventral surface of the curved embryonic disc. Moreover, it is getting closer to the vitelline duct, in the region that will become the future umbilicus.

The primitive intestine and heart have been obtained by folding of embryo, has the body wall already been completed as well?

1. The body wall is almost complete. It's complete in the rostral and caudal regions, but not in the central region where the midgut is still in continuity with the yolk sac. 2. The intraembryonic coelom is still in continuity with the extraembryonic coelom.

What are the causes of oligohydramnios?

1. The causes might be a diminished placental blood flow (reduced transudate from maternal blood flow), preterm rupture of the amniochorionic membrane (thinner membrane located in the basal portion of the amniotic sac, towards the cervix, made by the amniotic membrane and part of the chorion. 2. If this membrane, which usually ruptures just before delivery, when we say that the woman starts to lose the waters, breaks or is leaky there can be a reduced amount of amniotic fluid), renal agenesis (agenesis: absence of the kidneys), urinary tract obstruction.

Passage through the Vagina - Barrier 2:

1. The cervix (neck of the uterus) in comparison the rest of the uterus is narrow and has a mucus barrier created by glands. 2. At the period of ovulation the mucous of the cervix becomes more fluid to allow entrance of the sperm, at other periods the fluid is thicker and much more viscous, it acts as a protective barrier.

How does uteroplacental circulation form?

1. The cytotrophoblastic shell is colored in purple and we can see the spiral arteries pierce it, as to deliver blood inside the lacunae (light blue spaces). Inside some lacunae the villi have been portrayed. 2. Blood enters in a pulsatile (it's maternal circulation) jetlike way, and it spurts against the chorion plate and slows down diffusing around the villi, bathing them, allowing exchanges between the blood of the lacunae and the capillaries inside the villi. 3. Blood then exits through the open ends of the uterine veins that also penetrate the cytotrophoblastic shell, through which the blood can flow out. . The uterus as an organ, possesses both arteries and veins, also maternal veins are eroded by the process of invasion we discussed before and they communicate with the lacunae. 4. Intervillous spaces (lacunar spaces) contain 150 mL of blood, and is replenished, changed 3-4 times/minute.

What is the decidua?

1. The decidua is the endometrium which is changed because of the arrival of the blastocyst and the implantation (decidua = endometrium during pregnancy). 2. At the end of the menstrual cycle, some cells of the stroma become decidual-like cells (independently from the fact that the woman is pregnant or not). So, every month the uterine mucosa starts to prepare for a possible pregnancy.

Male infertility is detectable in

30-50% of involuntary childless couples.

THE BLASTOCYST (memorize this terminology): Solution

1. The embryonic pole = the side of the blastocyst where the embryoblast is located. 2. abembryonic pole = does not have the the embryonic tissue. 3. Inner cell mass: gap junctions between the cells. - inner cell mass = embryoblast (forms embryo tissues). 4. trophoblast: tight junctions = separation from the external environment (forms extra-embryonic tissues).

What is the structure of the final cord (umbilical cord) like?

1. The final cord is long around 50-60 cm and has a diameter of 2-2.5 cm. 2. The content is two umbilical arteries and one umbilical vein. That is because the fetal circulation is symmetrical, so that explains the presence of two umbilical arteries (originally there are also two veins but then one of them regresses). These structures are surrounded by a jelly-like substance, Wharton's jelly and enclosed in the amniotic sac.

Passage through the Vagina - Barrier 1:

1. The first problem experienced by the spermatozoa when deposited in the upper vaginal tract is that the pH of the vagina is quite acidic - low - (4-3). 2. This acidity is due to the secretions made by glands as well as the epithelial cells of the vagina which transform glycogen to lactic acid- therefore lowering the pH; this is a protective mechanism. 3. The spermatozoa do not fare well in an acidic environment, the fluids of the seminal fluid serve as a buffer, increasing the pH of the vagina (6-6.5) for a few minutes. 4. This brief increase in pH allows the spermatozoa to retain their motility; allowing them to approach the cervix.

What is the first step of cleavage?

1. The first stage of this process consists in increasing the number of cells by mitosis forming the blastomeres. (16 blastomeres form the morula, which takes 3 days to form). The cytoplasm (from the oocyte) is divided between an increasing number of cells called blastomeres 2. As the number of blastomeres (with each successive division) increase the nuclear/cytoplasmic ratio increases as the nucleus of these cells are very large in comparison to the cytoplasm. Cells get smaller in this process and the cytoplasm gets reorganized. The cells undergo compaction to ensure the maximum adhesion and cell to cell contact-mediated by cell-surface-adhesion glycoproteins. 3. Following this process, the outer blastomeres develop tight junctions, forming the trophoblast (the outer epithelial layer - the light blue cells in the diagram in the blastocyst stage), which will not be part of the embryo when formed but mediates the exchanges between mother and embryo and is important for adhesion and will form the placenta. Additionally the trophoblast produces the early pregnancy factor. 4. The inner blastomeres instead will develop gap junctions forming the inner cell mass which will be part of the embryo when formed. 5. Next, there will be a water transport inside the morula and a liquid filled cavity will be formed, blastocoel. Up to this point the whole complex takes the name of the Blastocyst.

FOLDING OF THE MEDIAN PLAN - HEAD FOLD: What happens because of the rostral bending of the embryonic disc?

1. The future brain starts to grow so much that it starts to grow over the oropharyngeal membrane, the heart, and the septum transversum, causing the rostral bending of the embryonic disc. 2. This bending causes a 180-degree inversion of the position of these three structures, which we see in the image above. 3. The septum transversum, which was the most rostral, now becomes the most caudal. 4. The heart goes ventral to the neural tube, but the position is in the middle. 5. The oropharyngeal membrane is now the most rostral structure. If you look at the images above, it's a 180-degree inversion. 6. In addition, the head fold causes the incorporation of part of the yolk sac into the body of the embryo, whereby a portion of the yolk sac (here called the foregut) comes to be positioned between the neural tube dorsally, the heart, and the oropharyngeal membrane ventrally. This portion of the gut tube of the intestine, see second image above, is called the foregut (the anterior or most rostral part of the gut or intestinal tube). So it's not surprising that we have the oropharyngeal membrane here because that is where the mouth is going to form (again, see second image above).

What happens once a secondary follicle has formed?

1. The granulosa cells which were expressing the follicle stimulating hormone receptor under the function of the FSH hormone starts to produce oestrogens. 2.The theca interna, under the action of LH, starts to produce androgens, specifically testosterone. 3. Because the formation of the antrum can distinguish different domains in the granulosa cells, the cells that remain surrounding the egg and the granulosa cells are called cumulus oophorus cells. Some of these cumulus oophorus cells remain surrounding the oocyte and the zona pellucida also when the oocyte is ovulated, and will form the corona radiata cells.

Why do we need a serosa around the heart? Or why do we need a serosa around the lungs?

1. The heart is a pump that needs something to cover it that allows for expansion. That's why we need a serosa. Similarly, lungs expand and compress. 2. The serosa has 2 layers: a visceral layer which is attached to the organ and a parietal layer. 3. These layers need to be able to slide on one another. That's why they produce a fluid between them that provides a sliding surface. This is the same for the heart and lungs. 4. For example, if a person has pleuritis (inflammation of the pleura), it's very painful and if not treated properly, the pleura (which is usually a small surface humidified) can transform into fibrous tissue in places and impair the expansion of the lungs.

What is the ovarian cycle and the uterine cycle?

1. The hypophysis, under the control of the nervous system and of the hypothalamus, controls the ovary, where we have the maturation of the oocyte and of the follicle surrounding it. 2. The production of the LH and FSH hormones(from the adenohypophysis) drive the maturation of the follicle, which produces hormones itself both before and after ovulation. 3. In the preovulatory phase much estrogen is produced, mostly by the granulosa cells, and peaks before ovulation. 4. After ovulation the estrogen production reaches a plateau, whereas progesterone levels increase and remain high. Much hormonal control. The endometrium also changes because of these hormonal changes.

Here the inner cell mass and outer trophoblast is well recognized:

1. The inner cell mass is characterized by gap junctions in between cells and can also be called the embryoblast because it will give rise to the embryonic tissues and then to the embryo. 2. The trophoblast is characterized by tight junctions and it is important because it creates a separation from the embryo to the external environment and also it will form the extra embryonic tissue that will not be part of the embryo.

What is spermiogenesis?

1. The last step of spermatogenesis where each spermatid matures into a single spermatozoa. 2. The importance of this step is the change of morphological characteristic -- made for speed. Spermatids undergo to postmeiotic changes in sperm morphology (acquiring a tail).

3 ovarian follicles: 1. The primordial follicles 2. The growing follicles (primary and secondary/antral) 3. The mature follicles (Graafian follicles) - usually the follicle that is going to release the oocyte at ovulation What are primordial follicles?

1. The majority of the follicles in the ovary at birth are primordial follicles - contain a primary oocyte (the oocyte which has entered meiosis I and has arrested at the first meiotic division). 2. These oocytes are surrounded by a single layer of follicular cells (follicular cells are somatic cells with a squamous layer, granulosa cells -- produce AMH, anti-mullerian hormone). 3. The diameter of this oocyte is around 30 µm at this stage. 4. While this oocyte enters the maturation process, it will become bigger and the follicular cells that surround it will undergo changes as well. 5. The reason why the oocyte becomes larger is because the cell starts to accumulate ribosomes, rER, nutrients, mRNA, fluids (in case that oocyte is the one that is going to be fertilized, it will have enough material to sustain the first steps of development of the embryo).

What are the 2 layers of the bilaminar embryo?

1. The most superficial of these 2 layers is called epiblast: formed by the cells that maintain the expression of nanog 2. The inferior of the 2 layers is called primitive endoderm (primitive = hints that there will be more) or hypoblast: formed by cells that at the beginning of the formation of the inner cell mass were expressing the transcription factor Gata 6.

How does egg/zygote transport work?

1. The newly captured egg or the zygote (fertilized egg) begins its journey from the uterine tubes (fallopian tubes) to the uterus, regardless if the egg will be fertilized or not, the transport along the fallopian tubes takes about 4 days. 2. The movement along the tubes is achieved through the contraction of the uterine tube (fallopian tube) smooth muscle (arranged in a spiral pattern) and the motile cilia (movement of cilia) of the tube's mucosa.

The prechordal plate and notochord are very important for the induction and patterning of the neural plate. How do they do this?

1. The notochord produces several factors (signalling molecules) that convince the ectoderm to become neuroectoderm; one of these is BMP-4. 2. On the boundary of the neural plate there are the neural crest cells, highly migrating cells, that will migrate in the rest of the body forming: A) All peripheral nervous system B) The medulla of the adrenal gland C) Part of the heart D) Bones in the skull E) Eye F) Melanocytes G) Teeth

The majority of the follicles in the ovary at birth are primordial follicles - contain a primary oocyte (the oocyte which has entered meiosis I and has arrested at the first meiotic division). Why is the oocyte stuck in meiosis I when it is at this stage?

1. The oocyte is stuck in meiosis I because inside the cytoplasm of the oocyte there is the second messenger* cyclic AMP (cAMP). *(messenger = molecules used by cells to communicate) 2. This second messenger is produced by the oocyte and by follicular cells surrounding the oocyte. 3. Cyclic AMP is important because it keeps the Maturation Promoting Factor (MPF) inhibited and as long as the MPF is kept inhibited the oocyte remains blocked at the initial part of meiosis I.

What happens during the Egg Capture?

1. The ovulated complex slides out of the surface of the ovary. 2. In close proximity to the ovary are the uterine tubes (aka. fallopian tubes); the segment closest to the ovary, known as the infundibulum, has many protrusions, known as fimbriae. 3. These projections are attracted, especially during the period of ovulation, to the surface of the ovary and sweep along the edges of it (sweeping movements of the fimbriae). 4. The ovulated complex is collected by these fibers and is pulled into the fallopian tubes.

Where is the paraxial mesoderm located and what does it develop into?

1. The paraxial mesoderm (near the central axis) doesn't develop in all the length of the embryonic disc, but just in the future trunk and head. 2. In the trunk it is going to go through a process called segmentation, which for example is going to give rise to vertebrae. 3. In the head segmentation is not going to take place because the mesenchyme in the head is more complex than the mesenchyme in the trunk.

What is the primitive circulation?

1. The primitive blood vessels that form in the level of the embryo start to be connected with the endocardial tubes (heart). 2. Everything starts at the third week when we start seeing the first blood vessels created by vasculogenesis (ex novo formation of vessels from mesenchymal cells) and angiogenesis (from a pre-existing vessel we have the sprouting of new vessels). This process begins in the extra embryonic mesoderm of the vitelline sac and in the connecting stalk and chorion (chorionic plate, cytotrophoblast and syncytiotrophoblast). 3. Two days later we start seeing blood vessels also in the embryo.

When we look inside the cortex of the ovary, we find 3 types of ovarian follicles:

1. The primordial follicles 2. The growing follicles (primary and secondary/antral) 3. The mature follicles (Graafian follicles) - usually the follicle that is going to release the oocyte at ovulation

What happens to the secondary oocyte?

1. The secondary oocyte contained in the follicle protrudes like a blister on the surface of the ovary and can acquire a size of 2cm. 2. There is a continuous accumulation of fluid in the antrum, the pressure continues to increase and follicular cells especially granulosa keep producing oestrogen. 3. These oestrogens are preparing the female genital tract for a possible fertilized egg and for transport of gametes before fertilization.

For what is the septum transversum important?

1. The septum transversum is important for the formation of the diaphragm (which separates the thoracic cavity from the abdominal cavity). 2. We also find the two endocardial tubes, on the right and on the left, and the future pericardial cavity. 3. There is also the oropharyngeal membrane. The rostral part of the neural plate is also there, which is still growing and will develop the brain.

By what factors is the process of somitogenesis driven?

1. This process of formation of the different compartments of somite is driven by a lot of molecular factors produced by the somite itself and by the surroundings. 2. The notochord releases Shh which triggers the production of Paraxis, which causes the downregulation of SNAIL transcription factor because we need mesenchymal cells to differentiate.

Why is it important to remember this relationship between the segments of the spinal cord and the somite?

1. The somites on the side of the spinal cord give rise to bones, joints, ligaments, muscles, and the dermis. 2. The spinal cord is divided into segments. 3. Each segment of the spinal cord gives rise to two spinal nerves: one on the right and one on the left. 4. Each segment of the neural tube in that region, which is the spinal cord at this point, innervates the cutaneous territory from the dermatome, the muscular territory from the myotome, and the bony-tendinous territory from the sclerotome, originated from the adjacent somite. 5. Imagine that, early in development, there is a segment of the neural tube, and on the side, there is a right somite and left somite. The nerves that originate from that segment of the neural tube start to make synaptic connections with the somite (with the myotome portion, the dermatome, and with the tendons that originate from the syndotome, etc). These connections established so early during development, also remain present in adult life, even when somites aren't present anymore. It doesn't matter if the dermis goes away from the spinal cord and moves to the surface of the body, as a sensory connection was established between that dermatome and the region of the segment of the spinal cord that was close to that somite. It doesn't matter if that dermatome then moved away and is distant from the spinal cord. The neural connection between that segment of the spinal cord and that stretch of skin is maintained. In fact, our skin has a dermatomeric organisation, which is important from the neurological point of view, as we will explore next semester. The same happens with muscle cells. If a bunch of muscle cells originate from a certain somite, there is an innervation from the spinal cord to that bunch of muscle cells. It doesn't matter how far the muscle cells go, that bunch of muscle cells will still remain innervated by the neurons of that segment of the spinal cord.

What is the process of somitogenesis?

1. The somitogenesis process is very complex. 2. First of all, it proceeds from rostral to caudal and it starts around day 20 (at the end of the third week, about to begin the fourth). 3. It starts in the paraxial mesoderm, specifically in a region which corresponds, more or less, to the boundary of the future trunk and of the future head.

How are spermatozoa released?

1. The spermatozoa, when released in the lumen of the seminiferous tubules, are then pushed by the pressure of the fluid in the seminiferous tubules, muscle contraction and ciliary movements towards the rete testis, the efferent ductules, and the epididymis. 2. It's mostly in the epididymis, where they will be stored for about 12 days, that the spermatozoa will mature and more specifically acquire motility and undergo further antigenic changes. 3. In order to mature properly and become motile, they need to reside in the epididymis for some days and then be stored in the lower part of the epididymis (it's a very long and coiled tube which then merges into the ductus deferens at its tail).

Characteristics of late primary follicles: What happens to the stroma?

1. The stroma that surrounds the granulosa gets organized into a theca (container). 2. The connective tissue organizes itself into a theca folliculi. 3. The theca folliculi is in turn organized into two compartments, one that is called theca interna and the other one that is called the theca externa.

Passage through the Cervix is divided into 2 phases: What is the slow phase?

1. The swimming movement of the spermatozoa moves them through the cervix (& cervical mucus) at a much slower pace. 2. Some get stuck in the crypts of the mucosa of the cervix and may only move through the cervix 2-4 days later.

What happens after neurulation?

1. The tail bud undergoes a process called secondary neurulation, through which the tail bud joins with the neural tube, forming the most caudal part of the neural tube. 2. The cells during development lose their pluripotency, because they choose a destiny. 3. At the beginning the epiblast expresses a lot of factors everywhere. 4. On one side some factors start to decrease, and this makes so that the primitive streak forms only on one part of the disc. 5. The disposition of these factors is regulated by body organizers: head organizer, trunk organizer and tail organizer. 6. The cranio-caudal axis is also controlled by Hox genes expression, which also are involved in the process of segmentation.

Why are the testis an immune-privileged organ?

1. The testis is an immune-privileged site that protects itself from auto-antigens and the associated detrimental immune responses by forming a blood-testis barrier. If the blood testis barrier is disrupted by a trauma, or if the barrier is simply inappropriate, sperm-specific antigens would be attacked by immune cells because they would not be identified as "self". This immune response could cause infertility. 2. The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility.

What makes the uterine tube (fallopian tubes) so important?

1. The uterine tube is very important, because if it is blocked because of scar tissue, the oocyte is captured and it cannot proceed and meet the spermatozoa. 2. Similarly, if it is already fertilized, the zygote cannot proceed to implant into the uterine cavity. 3. The blockage of the uterine tube can happen through infection and inflammation, which may be caused by sexually transmitted diseases, and by endometriosis(anomalous presence of endometrium in places that are not the uterus). 4. Blockages of the uterine tubes are a major cause of infertility in women.

2 masses of muscular tissue formed by the precursors from the myotome, what are they going to give rise to?

1. The ventral mass is going to give rise mainly to the flexors of the limbs, adductors (adduct = bring close to midline; abduct = move away from the midline), and to pronator muscles (pronation is when palm and forearm face down, supination is when palm and forearm face up). 2. The dorsal mass gives rise mainly to extensors (like triceps which help extend the arm or muscles used to perform extensions of the elbow joint), supinators, and abductors.

What is the yolk sac/vitelline sac?

1. The yolk sac is what remains of the blastocyst and it is located ventrally to the embryonic disc. 2. At some point of embryo development the wall of our yolk sac is lined internally by endoderm that is called Heuser's membrane or endodermal membrane and outside it starts to be enveloped by extraembryonic mesoderm. 3. Then at some point there was a process of cavitation between the extraembryonic mesoderm that would lead to the formation of the chorionic cavity or extraembryonic coelom.

What forms at the top of the tertiary vili?

1. Then the cytotrophoblast at the top of the tertiary villi starts to proliferate a lot, forming a sort of column at the apex of the villus, forming the cytotrophoblastic cell column. 2. They grow so much that they reach the periphery of the syncytiotrophoblast and start to grow over it, covering it to form a shell that surrounds the syncytiotrophoblast, that is called a cytotrophoblastic shell. 3. Some of the villi are attached to it. They are called anchoring villi while their minor branchings float inside the lacunae, filled with blood. 4. They are called floating villi. The lacunae and the blood inside them surround the villi.

The amount of amniotic fluid is of more or less ________ (at the beginning up around 10th week)

30ml

What is developmental fate?

1. Then there's the question of the developmental fate which is the type of cells to which normally a precursor CAN give rise. 2. A cell taken from the morula can become either an inner cell mass or a trophoblast cell (developmental potency), but when there's already the distinction, cells have already taken a certain developmental fate. 3. The more differentiation proceeds the more the cells' fate becomes limited. A cell taken from a morula can become both an inner mass cell or a trophoblast cell (related to image).

How is the spinal cord organized?

1. There is no physical separation among segments in the spinal cord, it is a continuity of neurons. 2. Nevertheless, we can appreciate the existence of a segmental organisation because each segment is characterised by its own sensory and motor routes and a spinal nerve.

What is established in the embryo by the 3rd week?

1. There's no precise boundary of what happens during the third week rather than the fourth week. 2. For example, gastrulation takes place mostly during the third week but then the last part of it, involving the caudal part of the embryonic disk, happens during the initial part of the fourth week. 3. By the end of the third week: the embryo is still flat so it's still an embryonic disk and through the process of gastrulation is becoming a trilaminar embryo. 4. The rostrocaudal (antero-posterior) axis will be established, as well as the dorsoventral axis. The dorsoventral axis is given by the fact that the epiblast in the second week was dorsal and the hypoblast was ventral; we can also look at it from a different point of view: in the 3rd week when the ectoderm is dorsal and facing the amniotic sac and the endoderm is ventral facing the yolk sac.

How do these precursors that migrate from the myotome form the muscles of the limb?

1. These precursors literally migrate in the limb bud and at the beginning, they form 2 masses of muscular tissue: one dorsal and one ventral. 2. Remember that we are talking about the embryo, so we normally use the terms ventral and dorsal.

How are the maternal and fetal side different?

1. They are different: the fetal one has a shiny surface, since it's covered by the amniotic membrane. Also, on the fetal side there's the insertion of the umbilical cord. 2. On the other side, there's no amniotic membrane and it's quite rough, because it is divided into territories. These regions on the maternal side are called cotyledons. Each cotyledon, at the core, corresponds to the presence of one, two or maybe three villi (the main tertiary ones with their branches) at the placenta.

What are the chorion and the placenta?

1. They represent a cooperative effort, sometimes very successful, sometimes not, established between the extraembryonic tissues of the foetus and the maternal endometrium, the decidua. These two things have to work together to have a functional placenta. 2. The outer wall of the blastocyst is the chorion or chorionic mesoderm: it is made of mesoderm, cytotrophoblast and syncytiotrophoblast, going from inside to outside. 3. The lacunae of the syncytiotrophoblast contain maternal blood and content of the glands of the endometrium, that provide nourishment of the embryo.

What are the specifics of how the sperm attaches to the oocyte?

1. This attachment to the oocyte membrane requires molecular recognition. On the head of the sperm there are proteins (receptors) called Izumo while the receptors (proteins) on the plasma membrane of the oocyte are called Juno. 2. Juno must attach to Izumo, and as soon as this recognition takes place and the spermatozoon content gets released into the oocyte, all other Juno receptors are eliminated and so no other spermatozoa can attach to the receptors because they no longer exist.

What is this image showing?

1. This image shows part of the embryonic disk, with part of the amniotic sac above, and part of the yolk sac below. 2. Image A contains the enlargement of the cranial region, whilst image B contains the enlargement of the caudal region of the embryonic disk.

What does this electron micrograph show?

1. This is an electron micrograph of the branches of one of those villi, that shows you the capillary network inside, with red blood cells. 2. After the fifth month we only have the syncytiotrophoblast and on its surface there are a lot of microvilli to increase the available surface of exchange between maternal blood in the lacunae and the blood which is in the capillaries of the villi.

What does this table show?

1. This is one of the typical tables which shows the different periods in which the embryo can come in contact with teratogens as well as the way it is affected (green = less sensitive; purple = highly sensitive). 2. The first weeks are very critical because of the formation of the heart.

How does the folding process occur (looking at this image)?

1. This is our embryo, with the amniotic sac dorsally and yolk sac ventrally. 2. At some point, the embryo does lateral folds which take place on the horizontal plane. 3. It also does a rostral fold and a caudal fold, which take place on the median plane. 4. Put together, the folds come together on the ventral surface of the body of the embryo in the region that will correspond to the formation of the umbilical cord.

What is the 4th week period susceptible to and why?

1. This period (fourth to eighth week), because of all these things that start to happen, is the window of time in which teratogens can cause major abnormalities since the embryo, once affected, may not die but it can continue its development carrying on these abnormalities (on the other hand, if it comes in contact with teratogens early on, the embryo usually dies). 2. In this period, tissues and organs differentiate very rapidly and therefore are more susceptible to teratogens.

How is the process of somitogenesis guided?

1. This process is guided by opposing gradients of proliferating and differentiating factors and also by gene expression. 2. Opposite gradients means that some factors are more concentrated rostrally than caudally and vice versa. 3. Since this process proceeds from rostral to caudal, the differentiating factors will be more concentrated rostrally while the proliferating ones caudally. 4. These factors are guided and turned on by sets of genes activated along the rostral-caudal axis. 5. At the beginning we have the formation of structures called somitomeres, around 42-44 pairs (we are talking about pairs since we have left and right paraxial mesoderm, meaning left and right somitomeres). The most cranial somitomeres (from 1 to 7 pairs) don't lead to the formation of somites and the caudal ones disappear. 6. Considering the number of somites formed, overall there are around 35-37 pairs of somites.

How does the process of the symmetry of the embryo breaking occur?

1. This process of the symmetry of the embryo breaking happens early on, during the embryonic disk stage. 2. At the level of the primitive streak we can observe that the primitive nodal cells are peculiar because, on their apical surface, they contain a cilium that is motile in the cells located centrally in the node and non-motile in the peripheral cells of the node. 3. In those cells in which the cilium is motile, the cilium bends in one and only one direction. 4. Motile monocilia bend towards the left establishing a flow in the primitive node that goes from right to left. In this case the inner structure of this type of cilia plays a key role since it contains a special type of dynein called "right-to-left dynein". This movement of the cilia in one direction causes a movement of fluid from right to left.

What are transcription factors?

1. Transcription factors are proteins that turn specific genes on or off depending by the necessity. 2. This process occurs by binding to near DNA. 3. Transcription factors can be activators boost or repressors for gene transcription, enhancers or silencers to turn genes on or off in specific parts of the body. 4. They help to decide in logic operations and combine different sources of information to decide whether to express or not a gene. 5. Transcription factors are the molecular bases for embryonic development.

The Factor Motility Protein induces, within the spermatozoa:

1. Tubulin phosphorylation 2. Increase of intracellular concentration of calcium 3. Increase in cyclic AMP (cAMP) A) Second messenger B) System of communication between cells C) Very small molecule, can pass easily between membranes and cells, moves easily in the cytoplasm

What are the vessels that carry blood to the inflow portion (entrance) of the cardiac tube?

1. Unbilical vein/s = the umbilical vein: connected to the placenta and through the body stalk carries blood to the inflow portion, it's richly oxygenated 2. Vitelline veins = the vitelline vein: from the wall of the vitelline sac and enters in the inflow portion of the heart, it's poorly oxygenated. 3. Cardinal veins: Segmental veins = Cardinal or segmental veins: originate from the body of the embryo and carry blood to the heart, poorly oxygenated. There is an anterior and posterior cardinal vein and a common cardinal vein that receives segmental veins from the body of the embryo. ***richly oxygenated blood (that comes from the mother) ***poorly oxygenated blood (blood that comes from the vitelline sack

Examples of maternal factors that can cause IUGR are:

1. Undernutrition (if the mother doesn't have nutrients for herself, she cannot provide for another human being) 2. Overnutrition (obesity, for example, can cause problems to the fetus) 3. Hypertension (if the mother is hypertensed the blood flow is not controlled and there may be too much blood flowing to the placenta) 4. Stress 5. Substance abuse (that can pass through the placenta and alter the development of the fetus)

So, overall, what, besides the primitive intestine has been obtained by folding the embryo?

1. We also obtained the heart now being ventral to the foregut. 2. The heart is in front of the esophagus. 3. The septum transversum (part of the future diaphragm) is caudal to the heart. 4. It forms the tendinous center upon which the pericardial sac and the heart lie.

So, overall, what has been obtained by folding the embryo?

1. We have obtained the formation of the primitive intestine by incorporating part of the endoderm of the yolk sac into the body of the embryo. 2. This includes the midgut - the central part that still communicates with the yolk sac. 3. It also includes the foregut, which is closed anteriorly by the oropharyngeal membrane, and the hindgut, which is closed posteriorly by the cloacal membrane. 4. These two membranes will break down at some point and form a communication between the foregut and the stomodeum (future oral cavity) and the hindgut and the proctodeum (future anal canal).

So, overall, what, besides the primitive intestine and heart has been obtained by folding the embryo?

1. We have obtained the full formation of the body cavities (the intraembryonic coelom) which is lined by a serosa in which one can recognize the parietal and visceral layers. 2. In a long time, this intraembryonic coelom will form the full pericardial cavity, pleural cavities (in the future thorax), and peritoneal cavity (the abdominal cavity).

FOLDING OF THE MEDIAN PLAN - HEAD FOLD: What is the anterior endodermal pocket?

1. We have the formation of an anterior endodermal pocket that will form the primitive foregut. 2. We call it an endodermal pocket because the yolk sac is lined by an endoderm. 3. So if part of the yolk sac is incorporated into the anterior part of the body of the embryo - which happens laterally, rostrally and caudally - we have the formation of an anterior endodermal pocket. 4. So part of the yolk sac with its endodermal lining comes to lie between the neural tube dorsally and ventrally what is becoming the future heart. 5. The foregut lies between the brain and the heart and is separated by the oropharyngeal membrane from the stomodeum (the future oral cavity).

What is the folding of the Median Plane - Tail or Caudal Fold?

1. We have the primitive streak (going from rostral to caudal), the cloacal membrane, and the body stalk with the allantois inside. 2. Now, again, there is a growth of the caudal part of the neural tube, which bends the caudal part of the embryo. 3. So now this structure comes to lie ventral to the body of the embryo, exactly like what happened in the rostral part of the embryo. 4. The new sequence has the connecting stalk with the allantois inside become ventral to the embryo and is the most rostral structure, followed by the cloaca and the primitive streak. 5. These three structures move ventral to the body of the embryo, and in doing so, due to the tail fold, another part of the yolk sac is incorporated caudally, which takes the name of the hindgut (primitive hindgut). 6. So we have the foregut (between the heart and the rostral part of the neural tube) and the hindgut (between the caudal part of the neural tube and ventrally the allantois, the primitive streak that is disappearing, and the cloacal membrane). 7. The central part of the intestinal tube (the one that is still connected with the yolk sac) takes the name of the midgut. 8. So due to the folding of the body of the embryo, we have the forerunner of the intestinal tube which is made by a foregut, a hindgut, and a midgut. 9. The midgut is the region of the intestinal tube that still maintains communication with the yolk sac through a narrow connection called the omphalomesenteric duct or vitelline duct or the yolk sac duct. 10. It is the narrow connection that remains between the central part of the intestinal tube (the midgut) and what remains of the vitelline sac. 11. Because of the folding of the embryo, the body stock with the allantois comes close to the vitelline duct. The body stock that has come ventral to the body of the embryo. Then, because of the folding, the communication between the midgut and the yolk sac becomes narrower and narrower and gives rise to the vitelline duct (or the yolk duct or omphalomesenteric duct). At a certain point, you can see that the body stock and the vitelline duct are basically attached to one another. That region where the body stock and the vitelline duct come together and attach to one another is the region where the umbilical cord is going to form. You should be consistent in the names you use: yolk sac/yolk duct, vitelline sac/vitelline duct or omphalomesenteric duct.

How does a cell know if it has to migrate towards the midline or closer to the lateral border?

1. When the embryo is flat, the notochord is medial and the lateral plate is lateral, but at some point during the fourth week there's the folding of the embryo which becomes a cylindrical structure: the embryo isn't flat anymore, but becomes a cylinder. 2. Therefore the organization of the structure changes from medial-to-lateral to dorsal-to-ventral. 3. For example, the notochord when the embryo is flat it's medial, but when the embryo becomes a roundish structure, with respect to the remaining part of the mesoderm, it's located dorsally because the lateral plate mesoderm becomes ventral.

What happens to the intestinal tube, while this folding is taking place?

1. When this type of folding takes place, the intestinal tube is suspended inside the serosa coelomic cavity by a dorsal and a ventral mesentery. 2. The professor highlighted the orange ring surrounding the intestinal tube, indicating that this is the splanchnic layer of the mesoderm. 3. When this layer comes together dorsal to the intestinal tube, it becomes the dorsal mesentery, which attaches the intestinal tube to the posterior body wall. 4. For a time, there is also a ventral mesentery that attaches the intestinal tube to the anterior body wall, but it will very soon disappear. The dorsal mesentery is another story. In some places it remains; in other places, it goes away.

What happens during the formation of the antrum?

1. While the antral cell follicle is forming the amount of receptors both on granulosa and theca cells increases. 2. See in this drawing that the theca interna cells start to produce testosterone, which crosses the zona pellucida reaches cells of granulosa and there by an aromatase, enzyme produced by granulosa cells, testosterone is transformed into oestrogen. 3. In the antral phase of the follicle, the growth of the follicle depends on gonadotropic hormones, FSH and LH. 4. Of all the growing antral follicles only one can survive to be ovulated.

What happens while the vertebrae are forming?

1. While the vertebrae are forming, they surround the future spinal cord. 2. In the meanwhile, the future spinal cord is starting to make connections with the periphery, forming the spinal nerve.

Transport of embryo to the uterus (for implantation):

1. Within 36 to 48 hours from fertilization the early pregnancy factor is produced (immunosuppressant). 2. By 48 hours the corona radiata is lost (zona pellucida is the only remained with zygote inside). 3. After 3 days the blastocyst is in the ampullary portion and from there it takes 8 hours to cross the isthmus. 4. In the meanwhile, the corpus luteum is being developed and produces progesterone which relaxes the uterotubal junction to help the blastocyst cross the isthmus.

Content of the umbilical cord at term is much simpler:

1. allantois is not there anymore 2. intestinal loop is not present anymore, gone back in the abdomen 3. the vitelline vessels are not there anymore.

The biochemical changes associated with the capacitation process include:

1. an efflux of cholesterol from the plasma membrane leading to an increase in membrane fluidity and permeability to bicarbonate and calcium ions 2. hyperpolarization of the plasma membrane 3. changes in protein phosphorylation and protein kinase activity increases in bicarbonate (HCO3 −) concentration and intracellular pH, Ca2+ and cyclic adenosine monophosphate (cAMP) levels.

Why do we need the amniotic sac surrounding the embryo and containing a fluid which is called the amniotic fluid?

1. buffer against mechanic injury (embryo and its tissue are quite delicate and the watery environment protects the embryo from the movement of the mother for example) 2. accommodates growth (it protects but is not so tight and so constrictive as to prevent the possibility for the embryo and the fetus to grow) 3. allows fetal movements (muscular-skeletal system development - watery environment that provides a bit of resistance to movement which helps to solicit the activation of musculoskeletal system) 4. permits normal fetal respiratory movements (the fetus doesn't breath because the lungs are filled with water, but it does respiratory movement, starts to practice -- promotes the development of the respiratory system = lungs) 5. protects the fetus from adhesion 6. acts as a barrier to infections, bacteriostatic properties 7. maintains a relatively constant temperature 8. assists in maintaining homeostasis of fluids and electrolytes

Why is cGMP important?

1. cGMP is important because it inhibits the enzyme phosphodiesterase (PDE3A). 2. If phosphodiesterase is not inhibited it will transform the cyclic AMP into the non cyclic form which is 5'AMP. 3. This is a problem because cyclic AMP inhibits the MPF so we don't want it to become 5'AMP before ovulation.

The hydatiform mole may be:

1. complete 2. partial

Surrounding the seminiferous tubules there is the interstitial space (stroma) of the testis, containing:

1. connective tissue 2. Leydig cells (endocrine) blood vessels 3. lymphatic vessels, nerves 4. cells of the immune system (important because they differentiate self-cells from other = non-self).

Some characteristics of the amniotic membranes that allow it to have its properties:

1. contains an essential number cytokines (some cytokines have antiinflammatory proteins) and essential growth factors (for example to regrow a part of the skin) 2. reduces pain when applied to a wound (antinociceptive properties) 3. increases and enhances the wound healing process (has antibacterial properties because one of the problems with wound of the skin is that they can get infected) 4. has antibacterial properties 5. is non-immunogenic (will not be seen as foreign material) 6. provides a biological barrier 7. provides a matrix for migration, support and proliferation of cells 8. reduces inflammation (presence of some anti inflammatory cytokines) 9. reduces scar tissue formation (usually a scar is made of loose connective tissue which causes a retraction of the skin which in turn for example can impair the movement of the region of the body)

Early in development the primitive heart is connected to three symmetric network of vessels:

1. embryonic network (in the body of the embryo) 2. vitelline network (in the wall of the vitelline sac) 3. umbilical network (in the body stalk, around the allantois, and it's the connection with the placenta and therefore to the maternal circulation).

Why study human embryology?

1. illuminates clinically oriented anatomy and explains how normal and abnormal relationship develop (bridge with pediatrics, obstetrics, perinatal medicine and clinical anatomy) 2. cancerogenesis may involve mutations or re-activation of genes involved in key development events 3. during development many defects can rise: genetic and environmental problems that may either kill the fetus or can impair the adult life

PERIODS OF HUMAN EMBRYOLOGY: There are 2 different ways to divide the period of human development: a medical method and an embryological one.

1. medical point of view: 3 trimesters (the ones into which pregnancy is divided) 2. embryological pov: comprehends 3 periods A) period of the egg: from fertilization to implantation (conceptus or pre-implantation embryo), through the phases of zygote, morula and blastocyst B) period of the proper embryo: from implantation (end 1st week) to 8th week C) period of the fetus: from the 8th week (2nd month) to the end of pregnancy. ***We should consider that development continues after birth, because organs are not mature yet (like the lungs and the Central Nervous System = CNS). And after it continues throughout our entire life.

Spermiogenesis is divided in 2 different categories of events:

1. nuclear events: change in the shape and size of nucleus, obtained by condensing chromosomal material (replacement of proteins -histones- that normally have to compact DNA with protamines to compact DNA even more). 2. cytoplasmic events: A) elimination of some cytoplasm to make spermatids lighter (sertoli cells phagocyte it = <another function of the sertoli cells>) B) formation of a head through condensation of Golgi apparatus at the apical end of the nucleus (the acrosome, filled with proteolytic enzymes to perforate the egg membrane and penetrate the cell during fertilization). C) formation of a tail (flagellum) on the other side of the centrioles with respect to the head; for spermatozoa motility D) spiral arrangement of the mitochondria in the proximal flagellum for energy production (so that the tail <flagellum> can move)

The myotome is divided into 2 territorites:

1. one that is more dorsally located and is called the epimere ('epi' = above). 2. the other is more ventrally located and is called the hypomere ('hypo' = below).

Make a diagram and then state: What are the main components of the female genital tract?

1. ovaries (where the oocytes mature each month) 2. Fallopian tubes (where only 1 mature oocyte is captured and may encounter fertilization) 3. uterus (either the unfertilized oocyte is expelled out of the body via menstrual periods; or the fertilized cell is implanted in the uterine wall) 4. cervix 5. vagina (Passage leading to the uterus by which the penis can enter (uterus protected by a muscular opening called the cervix)) 6. external genitalia

Clinical application of amniotic membrane:

1. patient with a lesion of the cornea and an amniotic membrane is put, literally sued on the surface of the cornea, resulting in a reasonable degree of lesion of the cornea (not perfect, but a good degree of healing) 2. We can therefore use amniotic membranes for other purposes than carrying the fetus.

Risk factors for ectopic pregnancies:

1. pelvic inflammatory diseases which cause the presence of scar tissue in the uterine tube and the formation of pockets and the embryo can get stuck in them 2. endometriosis 3. smoking (because it affects the motile cilia of the uterine tubes -- causing the zygote to implant in a place where it should not be)

Make a diagram and then state: What are the main components of the male genital tract?

1. penis (contains erectile tissue, becomes enlarged and hard, penetrates vagina, deposits sperm close to cervix). 2. epididymis (holds sperm until ready for ejaculation). 3. testis (where spermatozoa originate -- produce sperm and testosterone) 4. scrotal bursa (where testis and epididymis are contained -- outside the body = lower temp.) 5. Vas Deferens (Long tube which conducts sperm from the testes to the prostate gland (which connects to the urethra) during ejaculation) 6. prostate gland (Secretes an alkaline fluid to neutralise vaginal acids (necessary to maintain sperm viability)) 7. Seminal Vesicle (Secretes fluid containing fructose (to nourish sperm), mucus (to protect sperm) and prostaglandin (triggers uterine contractions)) 8. urethra (transports semen + urine out of the body) 9. ureter (transports urine out of the body) ***In particular, in the testis we can identify the seminiferous tubules, where spermatozoa are formed and mature; then they are carried to the epididymis and they enter the ductus deferens.

The zona pellucida is important because it:

1. promotes the maturation of the oocyte and the follicles (it forms very early and acts as a communicator between the oocyte and cells of the granulosa) 2. acts as a barrier that normally allows only one sperm to enter (prevents polyspermia), 3. initiates acrosomal reaction (actually, some acrosomal reaction begins before the contact between the two) 4. during cleaving the zona pellucida acts as a filter for the communication between the mother and the embryo 5. is an immunological barrier (there's a lack in histocompatibility between mother and the antigenically different embryo which therefore it is recognized as a foreign body from the maternal immune system) 6. keeps together the blastomeres until there are the proper type of junctions 7. facilitates differentiation of trophoblastic cells 8. prevents immature implantation (as long as zona pellucida = no implantation can take place). Do not want the embryo to implant in the fallopian tube, but later on in the uterus (site of implantation).

The lateral plate is going to be divided into two components:

1. splanchnic mesoderm 2. somatic mesoderm. Between these two components a cavity is formed and it is called "intraembryonic coelom" (which is in continuity with the extra-embryonic mesoderm).

what is the dorso-ventral patterning of the bilaminar embryo?

1. the epiblast is dorsal (back) and is on the side of the inner cell mass, that firstly implanted in the endometrial wall 2. the hypoblast is ventral (front)

In cross section, in the wall of the seminiferous tubules we can distinguish:

1. the lumen of the tubules (internal cavity); it is surrounded by somatic cells for support (Sertoli cells), spermatogonia and spermatozoa at different stages of maturation 2. the parenchyma of the tubules around their lumen; it hosts blood and lymph vessels 3. the stroma (connective tissue) of the testis with unicellular endocrine glands (Leyding cells) that produce aldosterone 4. the basal compartment towards the stroma, where spermatogonia and early primary spermatocytes are located 5. the adluminal compartment towards the lumen; here spermatogonia complete meiosis; while they move towards the lumen, they resemble more and more mature spermatozoa until they are released in the lumen.

We have to remember the existence of the vitelline sac not only for the story above but also because:

1. the primordial germ cells at some point are visible in the wall of the vitelline sac. 2. I can appreciate primordial germ cells in the wall of the vitelline sac, but first they are in the epiblast then in the wall of the vitelline sac, then they get back again inside the body of the embryo and will colonize the gonads. 3. In the wall of the vitelline sac we also have the formation of blood islands and vessels, in fact there is the vitelline circulation with the vitelline arteries and veins which are connected respectively with the outflow and the inflow portion of the cardiac tube. 4. And also for a while the mesoderm of the vitelline sac is a site of erythropoiesis (production of red blood cells). 5. By the 6th week of gestation the yolk stalk or vitelline duct loses contact with the gut tube: the connection between the vitelline sac (becoming smaller and smaller because we gradually become independent by it) and the intestinal tube is lost. 6. We got rid of the amniotic sac and fluid, we briefly discussed the meaning of the vitelline sac and now we need to say a few words about the allantois.

Meiosis is responsible for

1. the reduction in the number of chromosomes 2. the reassortment of maternal and paternal genetic material 3. further distribution of genetic information during crossing-over (meiosis I)

First example of the embryo taking charge:

1. there is a formation of two separate cell lines (trophoblast and inner cell mass) 2. polarization of the blastomeres (of 8 and 16 cells of the emrbyo) as we start to see that they develop a basolateral compartment (blue in the image) and an apical compartment (orange in the image) = meaning that they start to differentiate. Then when the numbers of cells increase the consequence is that some cells will lose contact with one another and lose the apical domain. (the relationship between cells changes) (specialization of the domains of the blastomeres -- basolateral and apical -- do not have to go into the detail of the diagram -- just that this is how the embryo is taking charge)

Sertoli cells have several other functions, meaning that if something happens to them, the process of spermatogenesis simply can't take place. They are not germ cells but nevertheless, they are very important in the overall economy of the seminiferous tubules. For example:

1. they secrete the tubular fluid inside the seminiferous tubules 2. they also produce an androgen-binding protein (not androgens because they are produced by Leydig cells, the unicellular endocrine glands found in the stroma of the testicles), which is very important as it may be available to the germ cells as they are maturing. Androgens are the group of sex hormones that give men their 'male' characteristics (collectively called virilisation). The major sex hormone in men is testosterone, which is produced mainly in the testes. 3. They produce and secrete other proteins for example: A) Retinal-binding proteins B) Mullerian-inhibiting factor C) Inhibin for feed-back loop to the hypothalamus 4. Another important role is the maintenance and coordination of spermatogenesis A) The Sertoli cells extend from the basal compartment up to the tip of the apical compartment and spermatocytes at different stages of maturation are literally embraced by the cytoplasmic processes of Sertoli cells B) Responsible for making sure spermatogenesis proceeds in the right way 5. Phagocytosis of residual bodies of sperm cells -- Spermatocytes' bodies, as they go through maturation to become spermatozoa, shrink in size in order to confer speed and lightness to the cell. To do this, they release cytoplasm which is then phagocytized by Sertoli cells.

The capillaries are connected to the:

1. · Umbilical arteries: carry blood from fetus to mother 2. · Umbilical veins: carries blood from the placenta to the foetus NB: the umbilical arteries have poorly oxygenated blood while veins have blood rich in nutrients and oxygen.

How does the neural tube form? Formation of the Neural Tube:

1.. From the neural plate there will be the formation of the neural tube, with an opening on the caudal part and one on the cranial part. 2. Of course, these openings need to close properly otherwise the brain is not going to develop. 3. The cranial neuropore closes after 23 days from fertilization and the caudal 2 days after the cranial one. 4. The formation of the neural tube is very complex and if some problem occurs the embryo is going to die.

REVISION OF 2ND WEEK: 10-11 days of development:

10-11 days of development: → Heuser's membrane that lines the cyst from the inside → amniotic cavity → in pink the extraembryonic mesoderm, in between Heuser's membrane and the cytotrophoblast.

REVISION OF 2ND WEEK: 11-12 days of development:

11-12 days of development: → the difference from letter A is that the extraembryonic mesoderm is also in between amniotic membrane and cytotrophoblast → within the mass of mesodermal cells some cavities start to form (lacunae)

then when we move on (up to 20th) it is around ______.

350ml

REVISION OF 2ND WEEK: 12-13 days of development:

12-13 days of development: → All the cavities come together to form one large cavity that separates the extraembryonic mesoderm in 2 layers: one remains on the side of the cytotrophoblast while the other remains on the side of the parietal mesoderm and of the yolk sac → the cavity is called chorionic cavity (formed within the extraembryonic mesoderm) or extraembryonic coelom. The outer wall of the blastocyst that now is formed by the extraembryonic mesoderm, the cytotrophoblast and a thin layer of syncytiotrophoblast takes the name of chorion.

As far as the formation of somites, it's important to know that each somite is going to be divided into:

2 territories, each of which is going to give rise to important derivatives.

Ejaculate is an average of

2-6 ml and is composed of sperm (less than 10%, usually around 100 million spermatozoa x milliliter) and secretion of the prostate glands and seminal vesicle -- These two glands produce many factors, nutrients, glycids which are important for the survival of the spermatozoa.

What is a hydatiform mole pregnancy?

2. Hydatiform mole = Problem in the development of chorionic villi, grapelike aspect. Presence of only paternal chromosomes or activation of only paternal chromosomes, may develop into choriocarcinoma A) Production of excessive amount of hCG B) Usually of paternal origin C) Oocyte inactive D) Some moles may develop after delivery or spontaneous abortion

Spermatogenesis takes

24 days

In relation to teratogens, pregnancy can be further divided into

3 periods; (1) resistant period (2) maximum susceptibility period (3) lower susceptibility period

Each month, from _____.

5 to 12 and up to 50 (different studies give different results) primordial follicles begin folliculogenesis, meaning they proceed in their maturation becoming growing follicles and entering the second category. 3 ovarian follicles: 1. The primordial follicles 2. The growing follicles (primary and secondary/antral) 3. The mature follicles (Graafian follicles) - usually the follicle that is going to release the oocyte at ovulation.

How many abnormal sperms are in the ejaculate?

5-20% abnormal sperms in the ejaculate.

The total length of the head and tail combined is

60 micrometers.

At the end (33th-34th week) around ______.

700-1000ml (not every fetus has the same amount of amniotic fluid, there is a range).

REVISION OF 2ND WEEK: 8 days of development:

8 days of development: cytotrophoblast in dark green, syncytiotrophoblast in light green. → While the blastocyst is implanting in the endometrium, the inner cell mass is changing: in yellow the hypoblast/primitive endoderm, in blue the epiblast → Formation of the amniotic cavity on the side on which the blastocyst is embedding

Once the spermatozoa enter the female reproductive tract they can remain there for up to

80 hours (3-4 days) to be used for a possible fertilization.

REVISION OF 2ND WEEK: 9 days of development:

9 days of development: → the amniotic cavity and the amniotic membrane are clearly visible → Formation of the parietal endoderm or Heuser's membrane: migration of cells to line from the inside the cytotrophoblast. → It's very difficult to see any discontinuity on the surface of the endometrium

What is choriocarcinoma?

A malignant form of trophoblastic disease - Carcinoma of the trophoblast during: normal or ectopic pregnancy, abortion or hydatiform mole. Non metastatic or metastatic (spreads to liver and brain)

What can anormal gastrulation lead to (an example of caudal displasia)?

Abnormal gastrulation can lead to some diseases, like Sirenomielia (it affects the caudal part of the embryo and also the last portion of the digestive tract and urinary tract, which means that something happened at the beginning of the 4th week).

What is the adhesion stage of implantation of the blastocyst?

Adhesion is when the trophoblastic cells and endometrial cells express adhesion molecules. This communication is important for the regulation of immunotolerance which is important as the embryo is semi-allograft (different from mother).

When can amniocentesis be done?

Amniocentesis cannot be done too early (before 15th week maybe 13th) because the amniotic fluid is too little.

Another problem that can arise with the amniotic membrane is the problem of:

Amniotic Bands

How do oocyte and follicular cells communicate?

An important thing that we need to remember is that the oocyte and the follicular cells surrounding the oocyte communicate with one another via microvilli and gap junctions (across the zona pellucida), so that cGMP produced by follicular cells can go inside the cytoplasm of the oocyte.

Body axes and planes of an embryo (1): What is this part of the body?

Anterior Posterior DORSAL and VENTRAL

What happens at the second trimester?

As we move to the second trimester of pregnancy, something changes. The amount of estrogen and progesterone produced by the corpus luteum is reduced, also because the corpus luteum gravidicum is starting to regress. The role of the placenta is becoming more and more important; there is still the production of some hCGs, but now also the placenta produces estrogen and progesterone. The placenta is helped in this by the fetal adrenal gland.

What happen at the different phases of the invasion stage of implantation of the blastocyst? At 7 days:

At 7 days (Invasion): 1. Blastocysts need to dig in the endometrium up to the lamina propria (limited invasion). 2. Cells of the trophoblast start to transform in 2 domains, one is the Cytotrophoblast and the other one of them is the Syncytiotrophoblast which develops only on the side where the blastocyst has been attached.

What happen at the different phases of the invasion stage of implantation of the blastocyst? At 8 days:

At 8 days: At this stage, Syncytiotrophoblast is very highly invasive and starts to digest the endometrium.

What happen at the different phases of the invasion stage of implantation of the blastocyst? At 9 days:

At 9 days: 1. At this stage Syncytiotrophoblast gets in close contact with maternal blood vessels and starts to erode them and the lacunae of it get filled with maternal blood and start surrounding the embryo. 2. In this stage there is a blood spotting possibility which can be disguised as an abnormal menstrual period (9 days after ovulation -- at a time when she would usually have her period again, but she is tricked <less bleeding but still> -- possible confusion of menstrual period -- does not mean that there hasn't been a fertilization at any time).

What happens to the communication between follicular cells and the oocyte at ovulation?

At ovulation the communication between follicular cells and the oocyte shuts down, therefore the system doesn't work any longer because phosphodiesterase is active and transforms cyclic AMP into 5'AMP, which is not able to inhibit any longer the Maturation Promoting Factor and therefore meiosis I can proceed and end.

What happens at the beginning of cleavage?

At the beginning of cleavage the embryo takes charge. At the beginning of cleavage, everything is dependent on the maternal factor ( for example the maternal mRNA) as the embryo is not still able to transcribe its own genetic material. Then slowly the maternal transcription goes down and then the zygotic material starts to be transcribed on its own and it becomes dependent on the genetic material of the zygote itself.

What happens at the beginning of pregnancy (first trimester)?

At the beginning of the pregnancy (first trimester), the corpus luteum produces both estrogen and progesterone which keep the female genital tract in the correct state, in order to promote pregnancy (for example, by not having menstruation). In the meanwhile, the future placenta starts to produce the human chorionic gonadotropin (hCG), which is important to sustain pregnancy.

What is still in the core of each somite?

At the core of each somite there are still mesenchymal cells that are going to differentiate later on in the process.

Learning outcomes

At the end of this lecture students should be able to • Define the organogenetic period • List and highlight the importance of the major key transitions of animal evolution • Define the concept of phylotypic stage • Summarize the key steps of the process of segmentation (somitogenesis) • List the derivatives of the components of the somite • Explain the relationship between somites and neural tube development • Describe the formation of the intraembryonic coelom • Outline the steps of the folding of the embryo and its outcomes: formation of the primitive intestinal tube, formation of the body cavities, formation of the body wall. • Describe the formation of the diaphragm. Developmental defects: congenital diaphragmatic hernia • Outline the general organization of the embryonic circulation. • Explain the difference between vasculogenesis and angiogenesis. Clinical drop: angiogenesis and vasculogenic mimicry in cancer

Why is the fetus not rejected?

At this point you don't have the tools to understand which are the mechanisms behind it. We can say that there are systemic events and local events. 1. The placental fetal tissues do not present foreign antigens to the mother's immune system. Most of the cells of the placenta do not trigger an immune reaction from mother because they lack antigens that mother recognises as foreign, for example the lack of the major histocompatibility complex (MHC), which, however, is present in the fetal tissue and in the placental stroma. 2. The maternal immune system cannot be repressed, because she would be continuously sick. However, at the local level (at the level of the placenta, for instance), some substances can be released in order to modulate the maternal immune response, with respect to the foreign antigens. For example, there can be the production of some local immunosuppressant molecules or a reduction of leukocyte trafficking (since leukocytes are cells that belong to the inflammatory response). 3. There are also some changes in the decidua, so that there is a barrier in the immune response. Some molecules are produced on the foetal placental surface that inactivate locally maternal immune cells. 4. So, if everything goes right, a compromise is reached between the development of the placenta and the one of the fetus.

What occurs because of the appearance of the primitive streak?

Because of the appearance of the primitive streak there's the determination of a lot of the body axes of the embryo.

What happens to the amniotic sac during the folding of the embryo?

Because of the folding of the embryo (caused also by the enlargement of the amniotic sac) the amniotic sac encloses and then completely surrounds the embryo. fetus surrounded by the amniotic sac (in the image)

What is segmentation?

Body parts that are repeated in animals with bilateral symmetry = takes place in the paraxial mesoderm and leads to somites formation. 1. The process of somitogenesis is the process of segmentation of the paraxial mesoderm (paraxial = on the side of the axes) -- Segmentation is one of the earliest morphological manifestation of a complex set up of gene expression that are to determine the basic body plan 2. In the embryo, macroscopic segmentation takes place at the level of the paraxial mesoderm. The paraxial mesoderm of the rostral region (head) remains un-segmented while the one of the trunk region undergoes segmentation.

What are the causes of Polyhydramnios?

Causes: 1. mostly the causes are unknown 2. maternal factors: diabetes (not controlled -> excessive amount of sugar in the maternal blood → passage of excessive amount of glucose in the fetal circulation → increased production of urine of the fetus trying to get rid of this excessive amount), cardiac problems (circulation of blood doesn't work as it should → problems in placental circulation), infections 3. fetal factors: oesophageal or duodenal atresia (esophagus or duodenum not completely developed → fetus can't swallow the fluid), anencephaly (lack of rostral part of our rostral nervous system development, because there was not the closure of the anterior neuropore → brain doesn't control swallowing), infections

SELF-EVALUATION questions: What are the blastomeres?

Cells that are formed during cleavage.

Clinical note - What can happen that goes wrong during the development of the notochord?

Chordomas could arise. 1. Some tumors may develop during the development of the notochord and they are called "Chordomas". 2. What happens is that pieces of notochord may be left in the base of the skull or in the vertebral column. 3. They have a slow growth, so when discovered they are clinically relevant, as they are already very large and cause a compression of the brain or of the spinal structures (= symptoms develop and worsen over time -- most common = headache, double vision).

Ultrasound measurement of embryo is called

Crown-Rump Length (CRL)

What do we see in this image? (SOL)

Cytotrophoblast from anchoring villi "invades" spiral arteries Modification of their wall: high volume flow at low pressure Fetal blood has a lower concentration of oxygen and a lower pO2 than maternal blood. Fetal hemoglobin has higher affinity for oxygen.

What can we see in the 5th week of development of the embryo?

Development of the limbs: In week 5 we can see a flipper-like upper limb bud which then, at the end of the week, turns into a hand plate (the distal portion of the bud flattens out and becomes a plate).

What can we see in the 6th week of development of the embryo?

Development of the limbs: Later on, during week 6, digital rays start to be visible even though they are still connected one to another through some membranes, which reminds us of our phylogenetic origins.

Clinical drop: Male Infertility

Disruption of the blood testis barrier (due to trauma, eg. through a sport injury) exposes blood to antigens (sperm-specific) not recognized as "self". Mounting of an immune response: sterility. A leaky or inappropriate barrier can also cause sterility.

monochorionic/monoamniotic twins

Division of embryonic disk, 1 placenta ,1 amniotic sac, 1 chorion identical twins that share the same chorion and amnion structures; separated late; high risk of problems

What are the different types of twins?

Dizygotic (2 eggs) - fraternal twins Monozygotic (1 egg egg, 2 embryos) - identical twins

What does the mature placenta contain?

During a delivery, after the baby is born, the placenta comes out. When we look at the placenta, it looks like a disc, with a fetal side and a maternal side.

What happens during ovulation?

During ovulation, the antral cavity becomes very big, so a lot of pressure is building up inside the large follicular cavity. Mature Graafian follicle is close to the surface of the ovary. 1. Cells that are on the side of zona pellucida of the oocyte maintain the name of corona radiata. 2. 10 to 12 hours before ovulation the cell was still arrested at the beginning of meiosis I, meiosis I resumes following the LH surge. Meaning that 10 to 12 hours before ovulation there is peak production of LH from the adenohypophysis, as well as a smaller FSH surge. 3. This hormonal peak acts upon cells of the follicle making it so that meiosis I resumes and is completed. 4. Cells of the cumulus oophorus respond to LH, because they have a receptor for LH and in response to LH they shut down the gap junction to the oocyte. 5. cGMP that was produced by follicular cells cannot be released any longer in the oocyte and this links to the activation of phosphodiesterase (PDE3A) that makes it so that the cyclic AMP that was inside the oocyte is transformed in 5'AMP, which activates MPF.

How the corpus luteum is formed: What is the corpus haemorrhagicum?

During ovulation, the theca externa, theca interna and some granulosa remain within the ovary and give rise to a very important structure: the corpus luteum("luteum" because of its yellowish colour). Right at the beginning of ovulation there is a haemorrhage of what remains of the follicle that released the ovulated oocyte, this structure is known as the corpus haemorrhagicum. This means that if you look at that area right after ovulation there are some micro hemorrhages.

What happens during somitogenesis to the mesenchymal cells?

During somitogenesis, mesenchymal cells of paraxial mesoderm undergo a mesenchymal to epithelial transition.

What happens in the 3rd week to the embryo?

During the 3rd week the body axes of the embryo are established. These axes are also determined by a lot of molecular events.

Dichorionic/diamniotic twins

Earlier separation: from 2-blastomeres to the morula stage. 2 blastocysts, 2 chorionic sacs, 2 amniotic sacs, 2 placentas 1. each have their own amnions and chorions 2. Splitting takes place before the blastocyst is formed: two blastocysts

What will happen after the formation of the amniotic cavity and yolk sac?

Earliest presence of blood vessels and blood cells in the extraembryonic mesoderm and body stalk At this stage of development we start to see the earliest presence of blood vessels and blood cells in the extraembryonic mesoderm followed by the body stalk: within the mesodermal cells, some of them are transforming into endothelial cells that start to delimit the lumen of very tiny vessels, while others are becoming red blood cells.

Disorders in amniotic fluid volume:

Either a reduced amount or an increased amount of amniotic fluid.

A note within the story: Phase 3 of Fertilization

Elimination of paternal mitochondria A process that must take place at this stage is the elimination of the sperm's mitochondrial genetic material (that had also entered the oocyte); this is because all of our mitochondrial genetic material (mitochondrial DNA) is maternal. *** We do not for sure how the mitochondria is eliminated in humans; but there are 2 models; all are eliminated, either immediately or progressively. Some are actively eliminated and others are diluted, depending on the species.

Percentage of extragonadal cell tumors:

Extragonadal germ cell tumors: Not just a matter of location. A review about clinical, molecular and pathological features = where they are found.

Sertoli cell respond to

FSH (hypophysis) and to testosterone (Leydig cells).

How do these hormones act on spermatogenesis?

FSH acts mostly on Sertoli cells, in the wall of the seminiferous tubules, while LH acts mostly on interstitial cells (Leydig, endocrine cells), in the connective tissue, stroma and vessels that envelope the seminiferous tubules. 1. Leydig cells, stimulated by LH, produce testosterone → androgen. Sertoli cells transform some testosterone into estrogens Some estrogens are carried back in a paracrine fashion to Leydig cells together with a stimulating factor. 2. Sertoli cells, stimulated by FSH, produce the androgen binding protein (ABP) and the anti-Mullerian hormone (AMH), which has an important role in the promotion of the maturation of spermatogonia in spermatozoa. FSH-stimulated Sertoli cells produce androgen-binding protein which binds testosterone and is carried into the fluid compartment of the seminiferous tubule where it exert a strong effect spermatogenesis. 3. Inhibin produced by Sertoli cells inhibits FSH secretion

The same thing is for granulosa cells, which start to express:

FSH receptors because it is mostly responding to the follicle stimulating hormone while the theca interna responds to the luteinizing hormone.

Newly released sperm cells are non-motile. They acquire motility in the epididymis by stimulation of the

Factor Motility protein (FMP) produced by the cells of the epididymis, inducing: (see image)

What are fetal complications caused by oligohydramnios?

Fetal Complications: pulmonary hypoplasia (fetus needs to swallow the right amount of amniotic fluid for the maturation of the lungs, the respiratory practice cannot take place correctly), limb deformities (the fetus can't exercise properly and the musculoskeletal system doesn't rightly develop and also because the amniotic fluid should protect: not enough fetus → squished limbs or any mechanical damage), facial abnormalities (not enough protection). Potter syndrome: pulmonary hypoplasia, limb deformities, facial abnormalities usually related to renal agenesis

MIGRATION is a complex mechanisms that requires dynamic rearrangement of the cytoskeleton:

Figure 2. Schematic representation of the different steps of cell migration on 2D substrates. 1. Polymerization of actin filaments at the leading edge is translated into protrusive force. 2. Membrane protrusion facilitates the binding of transmembrane cell surface receptors to the substratum components. New adhesions are rapidly linked to the network of actin filaments. 3. The combined activity of retrograde actin movement and contractile forces produced by stress fibers generates tension to pull the cell body forward. 4. The forces produced by the contractile network combined with actin filament and FA disassembly help to retract the trailing cell edge. Image courtesy of the Mechanobiology Institute, National University of Singapore

How do the blastocyst and the uterine wall interact?

For all of this to occur there has to be an interaction between the blastocyst and the endometrium. 1. The endometrium in this phase is undergoing decidualization. 2. Cells of the mucosa of the uterine (decidual cells) secrete many interleukins, growth factors and other factors that can be classified as supporting implantation (pro invasive) or inhibiting (anti invasive) to create a balance to regulate the syncytiotrophoblast so it doesn't corrode (= destroy / invade) the whole uterine wall -- we do not want the blastocyst to move all the way to the muscle layer.

What is a factor that can harm the initial part of gastrulation?

For example, ethanol (alcohol) can be a teratogen and lead to failure of the activation of Hox genes (they determine the placing of the parts of the body) and as a result there might be the disruption of SHH pathway, which causes a poorly developed brain (Holoprosencephaly) or Cyclopia.

Amniotic membranes can be used:

For the amniotic membranes anti-inflammatory and anti-angiogenic properties, you can use them for: 1. you can cover wounds and burns 2. in ophthalmic surgery 3. source of stem cells

Spermatogenesis

Formation of sperm (cells). From spermatogonia to spermatids. Takes place in the Seminiferous tubules of the Testis. The process of germ cell development during spermatogenesis can be divided into five succesive stages: (1) spermatogonia, (2) primary spermatocytes, (3) secondary spermatocytes, (4) spermatids, and (5) spermatozoa.

What happens after the repression of epithelial cells?

Formation of the endoderm. (A): a first wave of epiblast cells migrate through the primitive streak and substitute the cells of the primitive endoderm or hypoblast, giving rise to one of the 3 germinal layers of the trilaminar endoderm: the definitive endoderm → from the endoderm will originate for example trachea, lungs, pancreas, liver, digestive tract: formation of the epithelial lining of the digestive tube (for example enterocytes derive from the endoderm)

What is the first step in the THIRD WEEK: from a 2-layered to a 3-layered embryo through gastrulation?

Formation of the primitive streak and gastrulation. Gastrulation wird angekündigt by the formation of the primitive streak. The primitive streak is a linear band of thickened epiblast that first appears at the caudal end of the embryo and grows cranially. 15th day of gestation: → on the midline of the epiblast, but just in one half of it, a depression called primitive streak appears → made by a top region called primitive node in which there's a depression named primitive pit → following the node and the pit we find the primitive groove

How is the caudal section of the embryo formed?

Formation of the tail bud (Gastrulation takes place in a rostral to caudal manner = formation of the tail bud <caudal> is where Gastrulation ends): Gastrulation ends with the formation of a sort of a tail, called tail bud.

What is capacitation?

Freshly ejaculated sperms are unable or poorly able to fertilize so they must first undergo a series of changes known as capacitation.

What is the period of the fetus? (stage)

From the end of the 8th week of gestation (2nd month after fertilization).

What is the period of the embryo? (Stage)

From the implantation (end of the first week) to the 8th week.

Some primary follicles proceed their development and become...

GROWING FOLLICLES (aka) Secondary follicles!! 3 ovarian follicles: 1. The primordial follicles 2. The growing follicles (primary and secondary/antral) 3. The mature follicles (Graafian follicles) - usually the follicle that is going to release the oocyte at ovulation.

CRANIO-CAUDAL AXIS (A-P) is also controlled by

HOX genes expression.

High cAMP results in

High cAMP from oocyte and follicular cells Inhibits MPF (maturation promoting factor).

How do PGCs mismigrate?

Human embryo at 7 weeks after conception. 1. PGCs migrate from the yolk sac wall following the path of sympathetic nerve fibres towards the genital ridge, which will subsequently form the gonads. 2. PGCs failing to exit the nerve branches at the gonadal site may continue along the sympathetic trunk along the midline of the body and may end up in other distant sites, including the retroperitoneum, abdomen, anterior mediastinum, neck and midline of the brain. 3. Unless eliminated by apoptosis, these mismigrated PGCs can survive and give rise to GCTs in these various extragonadal sites

What is the disorder in amniotic fluid volume if it is reduced?

If there is a reduced amount the condition is called oligohydramnios (opposite of polyhydramnios).

What happens if these regions (sometimes are real morphological regions): head, trunk and tail organizers. are missing?

If these organizing regions are missing there will be problems in the development of that specific part of the embryonic body.

Image C:

Image C: within the mesoderm at the core of the villus there will be the development of a capillary network in communication both with the capillary network of the embryo and the blood in the maternal lacunae: it will permit exchanges between maternal and fetal circulation

What happens during the process of egg capture? What is left behind?

Important to bear in mind that this process of egg capture leaves behind the components of the mature follicle that will become the corpus luteum (theca interna, externa and granulosa) and only pulls the ovulated complex into the fallopian tubes.

What happens in the 3rd trimester to the fetus and the amniotic fluid?

In the 3rd trimester there is a turnover of the amniotic fluid every three hours. Therefore there is production and reabsorption → through amniochorionic membrane (forms between the amniotic membrane and the chorion) through the chorionic plate and because of fetal swallowing.

SELF-EVALUATION questions: Where does cleavage take place?

In the Fallopian Tubes.

What do we see in this image? (SOL)

In the above image the distinction between primary, secondary and tertiary villi is more evident. Villi are surrounded by maternal blood

Composition of amniotic fluid:

In the amniotic fluid we can find fetal epithelial cells (we can control from the genetic point of view by making a karyotype of the fluid), proteins, carbohydrates, hormones, enzymes, electrolytes, lipids and fetal lungs fluids (some of the fluids which are produced by the mucosa of the tracheo bronchial tree and the lung that is maturing then go into the amniotic fluid).

What happens at the third trimester?

In the final stage of pregnancy (third trimester), the corpus luteum is completely regressed and all the hormonal production is in charge of the placenta. The placenta also produces other hormones and hormonal-like structure, for example the human chorionic somatotropin or placental lactogen, produced by the syncytiotrophoblast, similar to the growth hormone produced by the adenohypophysis. This hormone is also important for the regulation of maternal glucose, which is useful for the growth processes because it is used by cells as a fuel. We need to regulate the amount of glucose and how it accesses cells for their growth. This hormone also prepares for the lactation process. Prostaglandins and other hormones are also produced by the placenta.

How is early pregnancy maintained at this stage?

In the meanwhile, the syncytiotrophoblast is producing a hormone to maintain corpus luteum and pregnancy (hCG is produced by the 8th day).

What must the embryo develop by the moment that it implants?

In the moment in which the blastocyst implants and the embryo starts to develop, the embryo must establish a 'parasitic' relationship with the mother.

What do we see in this image?

In this image, we can see a plastic image of the adult vertebral column and you can see the vertebral canal, which contains the meninges (darker blue structure) and the spinal cord inside.

What is the indadequate transformation of maternal vessels?

Indadequate transformation of maternal vessels by cytrotrophoblast cells leads to poor placental perfusion and underlies preeclampsia (hypertensive disorders) and certain intrauterine growth restriction of the fetus.

What harmful substance can also pass through the placenta?

Infectious diseases can also pass through the placenta. 1. An example is the ZIKA virus (ZIKV), which is one of those that can cross the placenta and reach the fetus. There are more mechanisms in which the virus can affect the fetus and they depend on the stage of development, because the placenta is not the same from implantation to birth, it undergoes many changes. 2. Among the potential outcomes of this infection there are microcephaly, which is the underdevelopment of both head and brain, intrauterine growth restriction, ocular abnormalities, also because the development of the eyes is related to the nervous system, fetal demise (fetal death) and long-term outcomes. This is summarised in the table below.

bilaminar embryo

Inner cell mass forms two Germ layers: -Epiblast -Hypoblast

How can a placenta abruption be seen?

It can be seen by the use of ultrasound.

PHASE 1: primordial germ cells (PGC) and their migration (form very early in an embryo). PHASE 2: increase in number of PGC by mitosis PHASE 3: reduction in chromosomal number (in the amount of DNA) by meiosis PHASE 4: structural and functional maturation of egg and sperm

It consists in the structural and functional maturation of gametes: sperm (spermatogenesis) and egg cell (oogenesis). Oogenesis & Spermatogenesis

What is the umbilical cord?

It is the structure that keeps the embryo and everything that surrounds it connected to the placenta, so its important meaning is obvious.

If fertilization takes place, the corpus luteum becomes...

It is very important, in this case, that the corpus luteum survives and develops for a long time to support the pregnancy. 1. It becomes the gravidic corpus luteum (GCL) and remains functional for 5-6 months, constantly producing progesterone and estrogen(important to sustain pregnancy). 2. The formation of this structure is stimulated by HCG (human chorionic-gonadotropin) that is produced by the syncytiotrophoblast cells of the early embryo. 3. As soon as the embryo is formed, there are some structures surrounding the embryo that communicate with the ovary hormonally, through the HCG, to sustain and foster the activity of the corpus luteum. 4. The GCL takes up almost all of the space within the ovary due to the amount of hormones that it needs to produce. 5. After 6 months gestation, the GCL regresses because there is the development of the placenta which replaces it as the hormone producing structure.

Where does apposition & adhesion take place?

It takes place in the site of the embryonic pole like the adhesion phase. Trophoblastic cells and endometrial cells express adhesion molecules there. In many sites of the endometrium, the glycocalix of the endometrial epithelium becomes thinner, microvilli disappear to prepare a flattened surface, pinopodes appear

What is the function of the fluid?

It's a sticky matrix made of hyaluronic acid, it has mechanical purposes but it also keeps together the cells of the granulosa surrounding the corona radiata. It still surrounds the oocyte after ovulation(the oocyte is surrounded by the corona radiata and in between there is still the fluid of the antrome).

What are conjoined twins?

Joined at some point

What is the third period?

Lower susceptibility period (weeks 9-38, fetal period) the basic plan of all organs is formed, possible functional derangement (alterations are not so macroscopically visible, we may have to wait for the baby to be born to see if he is affected or not)

What is the second period?

Maximum susceptibility period (weeks 3-8, embryonic period) teratogens can affect the development of organs, since this is when proper organogenesis happens (all the systems are really coming in to be -- organs are developed)

What happens after the formation of the endoderm?

Mesodermal migration At this point there's the endoderm, a middle empty layer and what remains of the epiblast, that is going to become the ectoderm. (B): the second wave of migration of the epiblast cells invaginates through the primitive streaks and starts to spread in between the endoderm and the epiblast. → This intermediate layer is called mesoderm (middle layer), even if it'd be more correct to call it a mesoderm mesenchyme because these cells are migrating mesenchymal cells (Mesenchyme is a type of undifferentiated connective tissue mostly derived from mesoderm. It can differentiate in connective tissue proper, bones, cartilage, cells of the circulatory system... still has to do a lot of migration = why it is undifferentiated).

SELF-EVALUATION questions: How does cleavage proceed?

Mitosis

All morphological aspects are driven by genetic material and by transcription factors. In the image below we can see 4 examples of transcription factors that are acting in the early embryo and are important to determine the cells that belong to the trophoblast or inner cell mass:

Molecular players in the formation of the first lineages in the blastocyst. Four lineage-specific transcription factors: 1. OCT4 at the beginning is expressed in all cells (colored in brown at the nuclei), when it reaches the stage of the blastocyst it becomes very much reduced in trophoblast but still present in inner cell mass. 2. Nanog at the beginning of cleavage is present in some cell blastomeres and some not -- this is what stochastic expression means -- (light blue), but when it reaches the stage of morula it is present everywhere. At the stage of the blastocyst in some cells of the inner cell mass is present but it's not present in the trophoblast. Nanog maintains undifferentiated cell stage (when necessary) and pluripotency of germ cells. It's almost undetectable when the primitive germ layers are formed. Nanog will become epiblast. 3. Gata 6 is a casual expression and has a similar process as nanog.

Where does the umbilical cord develop from?

Mostly, it develops from the connecting stalk or body stalk, where there is the formation of the umbilical vessels.

Now we start to fold the embryo, why?

Now we need to fold our embryo because at this point it's like a strange sandwich, where the inside of the sandwich is the embryonic disc, with the amniotic sac above and the yolk sac ventral. The situation cannot remain like this, so a process called folding takes place.

Oocyte maturation inhibitor

OMI (from granulosa to oocyte) follicular cell protein that reaches the oocyte via gap junctions and prevents the oocyte from undergoing spontaneous meiotic division Have to know the general concept of the diagram.

How long does it take for a new (another) pool of spermatogonia?

Once the pool has matured and has been released in the lumen of the seminiferous tubule, it takes more or less 64 days for us to see another pool of spermatogonia, in that same segment, at the same stage the pool before them was at when we observed it. It is around the same amount of time it take for spermatogonia to go through mitosis I, II and spermatogenesis

What is a monozygotic pregnancy?

One ova that divides. Mono-Mono babies mean they have the same sac. division of the embryoblast in 2 embryonic primordia, but 1 blastocyst with 2 inner cell mass 1 placenta, 1 chorionic sac, 2 amniotic sacs = Monochorionic Diamniotic twins Most common type of twinning (65%), begins at the blastocyst stage, by the end of the first week

How do you detect ectopic pregnancies?

One way to detect this is transvaginal ultrasonography to obtain detailed images of the organs in the pelvic region.

OVULATION.... (38h after LH and FSH surge)

Ovulation takes place because of the LH surge from the adenohypophysis. Large follicles, up to 2cm, are protruding on the surface of the ovary. Pressure of the fluids inside of the follicles combined with the substances released by the ovary and the follicle itself triggers an inflammatory response. Proteases and enzymes are produced which digest the outer wall of the follicle and surface of the ovary. Release of ovulated complex which is the secondary oocyte, zona pellucida, which surrounds the oocyte and a group of cells known as the corona radiata (which, before ovulation, are known as cumulus oophorus).

Explain the events taking place at ovulation

Ovulation usually occurs around mid-cycle, at approximately day 14-15 o Triggered by the LH surge Fimbriae of the fallopian tubes become stiff and scrap the surface of the ovary o Creates fluid filled currents which pulls the oocyte into towards the fimbriae where it will be caught and enter the fallopian tube o Cilia on the simple columnar cells beat the oocyte into the ampulla of the fallopian tubes o This will keep it localized in the area for fertilization to occur

What are the phases of gametogenesis?

PHASE 1: in the flat undifferentiated embryo some cells start to form: primordial germ cells; then they migrate. PHASE 2: increasing number of those primordial germ cells through mitosis. PHASE 3: meiosis (to reduce the amount of genetic material at 50% in order to make fertilization possible) PHASE 4: maturation of egg and sperm (we should consider how at the beginning of their life cycle spermatozoa are rounded cells and then they mature becoming tapered cells)

In some cases this process of invasion doesn't limit itself and proceeds in the wall of the uterus, which leads to...

Pathological Placenta.

What happens during the first phase of fertilization?

Phase 1: Penetration of the Corona Radiata 1. As spermatozoa come close to the oocyte, they first encounter the cells of the granulosa: the corona radiata. 2. Spermatozoa start to anchor between one cell and another in the corona radiata. They swim very aggressively to wedge themselves between the cells and the acrosome (derivative of the golgi apparatus -- acrosome is inside the cytoplasm) starts to release some hyaluronidases (enzymes) which start to slowly digest away through the corona radiata. 3. The mechanical effect of the swimming movements combined with the chemical effect of the enzymes allows the spermatozoa to push through corona radiata. 4. It appears that also some enzymes of the uterine tubes may contribute to this process.

What happens during the second phase of fertilization?

Phase 2: Attachment and Penetration of the Zona Pellucida. 1. Spermatozoa bind to the zonal proteins of the zona pellucida (Zp3) which are species-specific (human-specific) - the introduction of sperm from any other species would not be able to bind to the zona pellucida because they would not be recognized. 2. The binding of the spermatozoa to the zonal proteins triggers the complete/full acrosomal reaction (that was already partially taking place before). 3. The acrosomal reaction: Inside the cytoplasm of the sperm there is a huge increase in the calcium concentration which causes an increase in intracellular pH of the spermatozoa; this pH increase causes the membrane of the acrosome to fuse with the membrane of the head of the sperm which allows the release of acrosomal enzymes towards the zona pellucida. 4. The penetration of the sperm through the zona pellucida is due to the digestive properties of the acrosomal enzymes (eg. acrosin) previously mentioned, and the constant swimming motion of the sperm. 5. They do not immediately reach the oolemma (plasma membrane of the oocyte); instead, the sperm now enter the perivitelline space. More than one spermatozoa can complete this phase and enter into the perivitelline space but only one is able to fertilize the egg.

What happens during the third phase of fertilization?

Phase 3: Binding to the Oocyte Membrane and Fusion of the spermatozoon and Egg 1. One of the spermatozoa binds to the microvilli of the membrane of the oocyte; this binding allows the membrane of the spermatozoa to fuse with the plasma membrane of the oocyte and the content of the sperm gets released into the cytoplasm of the oocyte. 2. All components (the contents of the spermatozoa) of the spermatozoon enter the egg except for the membrane: Head (nucleus), midpiece (largest part, where mitochondria are arranged in a spiral fashion) and tail enter the cytoplasm of the oocyte.

What happens during the fourth phase of fertilization?

Phase 4: Prevention of Polyspermy (& activate the oocyte). 1. (usually present in lower animals -- a method to prevent polyspermy, but potentially also present in mammals = humans) Fast block: The membrane electrical potential (all the cells in our body have one) of the oocyte is altered, it is depolarized going from -70 to +10, this lasts a very short period of time, only a few minutes and so is only able to prevent adhesion. It is not very successful. 2. (more probable mechanism of preventing polyspermy in mammals) - Permanent block: Due to the depolarization of the membrane, waves of calcium begin to enter into the cytoplasm of the cells (increased calcium concentration = egg activation). 3. Below the plasma membrane of the oocyte, when it develops from the primary follicle to the secondary follicle, there is the formation of cortical granules. 4. During permanent block these granules fuse with plasma membrane of oocyte and release their content into the perivitelline space, where there are the other spermatozoa waiting. 5. This release causes the once loose fluid of the perivitelline space to become tough and sticky, and hence entrap any other spermatozoa that are in the perivitelline space, preventing them from coming in contact with the membrane of the oocyte. 6. Swilling of the space: The perivitelline space also swells in this stage, increasing the physical distance between the sperm and the plasma membrane of the oocyte. 7. Zona Reaction: Hydrolyzation of sperm receptor proteins: the receptivity of the plasma membrane and the zona pellucida of the oocyte are changed, so the spermatozoa outside the zona pellucida can no longer attach to it. Only one spermatozoon will enter the egg, both because the other spermatozoa are trapped in the perivitelline space and because Izumo and other receptors on the membrane have been removed.

What is the placenta accreta?

Placenta accreta: it occurs when the placenta starts to invade also the myometrium, which is just below the endometrium. There's a normal pregnancy, but at birth the placenta removal can cause haemorrhages.

What is the placenta increta?

Placenta increta: it progressively penetrates the myometrium.

What is the placenta percreta?

Placenta percreta: complete invasion of the myometrium and even this progressive formation of the placenta extends behind the myometrium in what is called the perimetrium (serosa that surrounds the uterus) and, from there, it can even invade the surrounding organs, like rectum or bladder.

What is the placenta previa?

Placenta previa: attachment at the level of the neck of the uterus, so the internal uterine os. The wall of the uterus doesn't have the necessary characteristics to host a fetus, it is too small. At delivery, the neck of the uterus tries to elongate to become a birth canal for the passage of the fetus. It can cause blood vessel rupture during late pregnancy. The mother may bleed to death, the fetus may suffer because of reduced blood supply and it usually requires a cesarean section. Sometimes, to remove the placenta there, it is necessary to remove the uterus.

What is the disorder in amniotic fluid volume if it is increased?

Polyhydramnios excessive amount of amniotic fluid.

What is the amniotic fluid?

Present in the amniotic sac and has a complex composition and depends very much on the gestational age of the fetus.

What is oogenesis?

Process by which ova are produced by the female. Involving the maturation of the oocyte. But also the maturation of the follicle, so the somatic cells (cells surrounding the oocyte), which together form a morpho-functional integrated unit.

What are HOX genes and what do they do?

Regulation genes; tells body where to grow legs, wings, arms, head; determine body plan, how to turn embryo into adult 1. There's also a cranial to caudal expression of specific genes, such as HOX genes, which are evolutionarily conservative genes, meaning that they work very well. 2. They were firstly studied in the fruit-fly, then in other vertebrates and mammals and then in humans. 3. These genes help to determine, for example, the rostral-caudal axis of the embryo.

What happens after the formation of the primitive streak and gastrulation?

Repression of epithelial features. 1. The expression of some genes that are able to attach to specific regions of the DNA can be used to repress genes that code for epithelial features (such as junctions or polarization). → For example Snail is a transcription factor called zinc finger transcription factor because it has a zinc molecule embedded in its overall structure.

What is the first period?

Resistant period (weeks 1,2) all or none response, either the embryo dies or survives unaffected.

Body axes and planes of an embryo (3): What is this part of the body?

Sectioning the embryo A) Transverse sections B) Median or sagittal sections C) Coronal or frontal sections

When is segmentation visible?

Segmentation is clearly visible during the fourth week, but then it pretty much disappears because the somites, later on, give rise to several structures of the body.

The adluminal and basal compartment are kept separated by processes of the ______ .

Sertoli cells, which come in very tight junctions

In this new formed structure we will find the elements that were present previously in the two separate ducts:

So not only the umbilical vessels, but also the allantois. The vitelline duct is still visible as well.

Now let's look at the embryo from above, just like in this picture beside (and not from a cross-section anymore). We can see what is happening in the lateral plate mesoderm.

So, we see that the process of vacuolation is taking place in the lateral plate mesoderm, leading to the formation of a cavity that has a horseshoe-shaped appearance (look at the shape of the arrows). This curved structure can be divided into compartments. The curved part (at the top), which is developing close to where the future heart is developing, is going to become the pericardium cavity (an important serosal cavity). The two limbs (lower part of the horseshoe) will give rise to two structures. The initial/middle part of the right and left limbs will give rise to the pericardio-peritoneal canals, which in adults become the pleural cavities (the pleura are the smooth surfaces that surround the lungs). The distal part of the limbs (the last part of right and left limbs) will give rise to the intraembryonic coelomic cavity, which will be the one that will be located in the peritoneal cavity of the abdomen.

THERE CAN BE ONLY ONE....

Some growing follicles degenerate ...and some enlarge mainly by taking up fluids.

What happens to some mesenchymal cells?

Some of the mesenchymal cells in the wall of the yolk sac, in the body stalk, in the chorion don't form vessels but start differentiating into endothelial cells and then the tissue around them is going to form the additional layer of the vessel wall = this process is called vasculogenesis; the formation of entirely new blood vessels from precursors.

What is the Period of the egg? (Stage)

The period of the egg is from fertilization to implamantation (conceptus or preimplantation embryo): zygote, morula, blastocyst.

Fertilization:

Sperm and oocyte meet in the ampulla, in the uterine tube, where the embryo must NOT implant (tubal pregnancy that would lead to a massive hemorrhage due to the growth of the embryo).

How are sperm attracted to the oocyte?

Sperm are attracted towards the oocyte because of chemical and thermal stimuli: 1. Sperm chemotaxis is a form of hormonal signalling (chemical "smelling"/attraction) where the spermatozoa respond to cumulus oophorus (egg-derived chemicals = derived from progesterone and chemoattractants) released from follicular cells (corona radiata), oocytes, and the fallopian tubes. 2. They also respond to a temperature gradient; the temperature is higher where the oocyte is.

What is a spermatogenic cycle?

Spermatogenic cycle is the time it takes for the reappearance of the same stage within a given segment of the tubule. - spermatogonia enters cycle at fixed intervals - adjacent regions of tubule are advanced or retarded Because cells, maturing spermatogonia and then spermatocytes, are linked by cytoplasmic bridges (until they are released in the lumen of the seminiferous tubules), they communicate with one another and they are associated in the same stage. So when I look inside a certain segment of the seminiferous tubule, all the spermatogonia and spermatocytes are going to be at the same stage of maturation. In another segment they will be at another stage, depending on when each pool of spermatogonia entered meiosis I. The reappearance of that same association in that same segment is defined as a spermatogenic cycle.

What can happen after the formation of the earliest presence of blood vessels and blood cells in the extraembryonic mesoderm and body stalk?

Spontaneous abortion or miscarriage: Spontaneous abortion or miscarriage is pregnancy loss that occurs naturally before the 20th week of gestation. → It's most common during the third week after fertilization → Approximately 25/30% of recognized pregnancies end in spontaneous abortion, usually during the first 12 weeks. → Frequency of early spontaneous abortion is difficult to assess because a spontaneous abortion occurring several days after the first missed period is often mistaken for delayed menstruation → More than 50% of known spontaneous abortions result from chromosomal abnormalities incompatible with the progression of the pregnancy → Other causes: failure of the blastocyst to implant: the blastocyst is there but it can't implant because the endometrium is not responding as it should or is inflamed or even because there's lack of immunotolerance. → When we reach a certain level of development and can talk about fetuses, the higher incidence of spontaneous abortion is due for example to neural tube defects , cleft lip or cleft palate (severe disfunction in the formation of the roof of the oral cavity or of the lip) → After the 10th gestational week 25/40% of spontaneous abortions are related to fetal causes, 25-35% to placental causes (it's not developing as it should, it does not attach properly or it doesn't supply the right amount of nutrients), 5-10% to maternal causes (may be related to the placenta or to some maternal diseases) and the rest remain unexplained

Body axes and planes of an embryo (2): What is this part of the body?

Superior and inferior CRANIAL and CAUDAL (the term "caudal" is used because at a certain point of embryological development we have a tiny tail. This is due to ontogenesis, which is the development of a human body passing through the process of phylogenesis, the development of the phylum to which human beings belong)

What happens after the second week of the embryo (fertilisation and early stages of embryo development <week 1 and 2>and implantation)?

THIRD WEEK: from a 2-layered to a 3-layered embryo through gastrulation The third week is a very critical week because it involves gastrulation, a process that transforms the bilaminar embryo made by the epiblast and the hypoblast into a trilaminar embryo.

Something can go wrong in the process of maturation and migration of PGCs:

TUMORS Some of the tumors that originate in the PGCs can have tissues from the body on them (embryonic tissues) = Teratomas.

Teratomas are:

Teratomas are a type of germ cell tumors and include components/tissues (eg. eyes, hair, tooth, etc.) derived by the 3 embryonic layers (ectoderm, mesoderm and endoderm): they can form in the gonads or in extragonadal site. PGCs are pluripotent germ cells that can give rise to different tissues

How big is the (mature) placenta (at birth)?

The available surface of the placenta, considering all the villi, is more than 10 square meters. If you look at it macroscopically, it has a diameter (since it's sort of roundish) that measures 15-20 cm, its thickness is around 3 cm and the weight, that depends on the level of development of the placenta, in general is around 500-600 g.

Where do the axial bones originate?

The axial bones, meaning the vertebral column, originate from the somite.

2RECAP (up until now):

The blastocyst was progressively implanting in the endometrium of the uterine wall and, because of that, the endometrium was fully changing: in order to become a decidua it has to create the right environment for the future fetus to develop.

What are the vessels that carry blood to the outflow portion (exit) of the cardiac tube?

The blood that the heart receives is mixed: medium oxygenated blood and it's going to be distributed to the embryo. 1. Vessels from the outflow portion of the cardiac tube: what comes out is "purple". 2. This region of the primitive heart is called the aortic sac, connected by a system of vessels (pharyngeal arch arteries) to the dorsal aortae (in the early phases there are 2 aortae because the network is symmetric). 3. From the dorsal aortae we have the origin of intersegmental arteries that go to the tissues and organs of the fetus. 4. Then we have the formation of the vitelline artery, called vitelline because it goes to the wall of the vitelline sac. 5. We also have the umbilical artery that goes from the dorsal aortae to the placenta.

What is the decidual reaction?

The decidual reaction is how the endometrium changes because of the implantation of the blastocyst to nourish the embryo and form an immune privileged site. Because of the implantation the endometrium is then divided into compartments: 1. the decidua basalis (side of endometrium where embryo implants) 2. the decidua capsularis (after embryo implanted to cover it) 3. the decidua parietalis (rest of decidua where the embryo is not implanted).

How do the dorsal and ventral mesenteries form?

The dorsal mesentery, which suspends the intestinal tube inside the future peritoneal cavity (in the abdomen), is important to remember because it contains the vessels and nerves which are directed to the intestinal tube.

What does the end of the 4th week of development of the embryo mark?

The end of the fourth week, for the human embryo, marks the phylotypic stage, which is the stage in which all vertebrates, more or less, look alike. This is called evolutionary hourglass.

What changes does the endometrium undergo as the blastocyst reaches it?

The endometrium undergoes a lot of changes when the blastocyst reaches it. 1. Fibroblasts in contact with the syncytiotrophoblast become bigger, rounded and epithelioid-like as they become filled with fluids, lipids and glycogen and form a sort of massive cellular matrix that surrounds the blastocyst and embryo which will change the lamina propria of the whole endometrium occupying it. 2. These changes are important for the formation of placenta (to provide some nutrients at the beginning of its formation) and also important to form an immune privileged site.

Envelopment of the body of the embryo by the amniotic sac is complete in:

The envelopment of the body of the embryo by the amniotic sac is complete only in the rostral and caudal regions of the embryo because in the central region of the embryo we need to maintain communication between the intraembryonic coelom and the extraembryonic coelom for a few weeks.

What will the epiblast and hypoblast give rise to?

The epiblast and hypoblast will give rise to different derivatives, as we'll see better during the third week with gastrulation, the process through which the embryo becomes trilaminar.

What does the heart of the embryo look like in the fourth week period?

The heart of the embryo, a very simple tubular structure.

What muscles originate from the hypomere?

The hypomere gives rise to the hypaxial muscles, which are the muscles that form the lateral body wall (like the large muscles on your belly, the internal oblique, the external oblique, transversus abdominis, the recti muscles). These have a hypaxial origin.

What happens during the 2 week to the embryo?

The inner cell mass of the blastocyst is going to become the embryo and the future fetus. Development of the bilaminar embryo and full implantation During the second week, the embryo becomes a bilaminar disc: the cells of the inner cell mass differentiate as to become a sort of flat ovoidal structure made by 2 layers.

Explain the formation of the corpus luteum and its role:

The luteal phase occurs in the second half of the cycle at approximately day 15-28 o Graafian follicle which expels the oocyte (corpus hemorrhagicum) will be stimulated by LH to accumulate cholesterol, lipids and fats, which cause it to become yellow o It will become the corpus luteum which will be further stimulated by the corpus luteum to produce progesterone

Where do muscles from the limb originate from?

The muscles of the limbs, upper and lower, originate from the migration of the myoblast in the limb buds of the hypomere portion of the myotome.

What does the myotome give rise to?

The myotome gives rise to muscles; Myoblasts need to leave the myotome in order to give rise to muscles.

How will the neural tube undergo segmentation?

The neural tube adjacent to the somite will be divided into functional segments, which are the spinal cord segments, which we introduced before.

What is the normal site of implantation of the embryo?

The normal site of implantation is in the posterior wall of the uterine cavity.

What are the different stages of the development of the notochord? Notochord Formation:

The notochord (considered part of the mesoderm) elongates in front of the primitive node, and undergoes through a series of stages: 1. First it becomes a hollow structure (a tube) 2. Then it fuses with the endoderm and it opens 3. It becomes again a tube, but with a much narrower lumen 4. At the end it becomes a filled tube

Notochord vs. Prechordal plate

The notochord and the prechordal plate form on the midline of the embryonic disc. They are important because they have inducing and patterning properties. Notochord: Tubular structure elongating in front of the primitive node Prechordal cells: group of cells that associate with the anterior visceral endoderm

What types of properties does the notochord have?

The notochord has inductive properties with respect to the neural plate, predecessor of the nervous system, and patterning properties, as it tells each cell what part of the nervous system is going to form. NOTOCHORD: plays important inductive and patterning roles in the early embryo (axial skeleton, neural plate ...)

Which is the theca externa?

The outermost part of the theca folliculi, theca externa, is a capsule of connective tissue that has a protective function.

What are pathological placentas?

The placenta can be pathological (abnormal) and this can be the source of abnormal vaginal bleeding. There are different types of placentas.

What is somitogenesis?

The process of somitogenesis, meaning segmentation from rostral to caudal of the paraxial mesoderm, is guided by the progressive expression of some genes among which the previously mentioned HOX genes.

The protein ____ helps...

The protein dynein helps spermatozoa with their overall motility: when microtubules are bending, dynein is active and attached to them.

FOLDING OF THE MEDIAN PLAN - HEAD FOLD: What is the septum transversum?

The septum transversum is the forerunner of the diaphragm, and the heart is above the diaphragm. Looking back at this image, the septum transversum is now ventral and more caudal, and the heart and pericardial cavity are rostral to the future diaphragm - everything is coming to be in the right position.

FOLDING OF THE MEDIAN PLAN - HEAD FOLD: Where does the septum transversum lie now?

The septum transversum now lies caudally to the heart. It will develop in the tendinous center of the diaphragm. The formation of the diaphragm is very complex. The diaphragm does not originate only from the septum transversum, but the septum transversum is very important as an organizer and will give rise to the tendinous center of the diaphragm. The diaphragm is a large muscular plate that has a tendinous part at the center. Upon the tendinous part of the diaphragm, we have the pericardial sac with the heart inside.

What happens to the symmetry of the embryo at a certain point during its development?

The symmetry of the embryo is broken at a certain point of its development, the position of some organs becomes asymmetrical.

Which is the theca interna?

The theca interna is the one closer to the membrana granulosa and is the portion that is undergoing the most changes, for example: 1. It becomes highly vascularised 2. The fibroblasts (a type of cell that contributes to the formation of connective tissue) start to change and have a glandular appearance 3. The cytoplasm swells 4. Liquid droplets can be found inside 5. Produces androgens under the control of the luteinizing hormones (LH) because its cells start to express LH receptors.

What is the structure of the umbilical region?

The umbilical region is wider at the beginning, since the stalk and the yolk duct are still separated, but as growth and folding takes place more and more, the body stalk and vitelline duct really come to be attached.

What does the word "asymmetric" in the scheme, next to "tertiary villus" highlight?

The word "asymmetric" in the scheme, next to "tertiary villus", is to highlight how this development is not homogeneous, but it is different in the chorion frondosum and in the chorion laeve. The chorion frondosum is made of tertiary villi, that will not form on the other side of the embryo (they form only on the side of the decidua basalis).

What is the zona pellucida?

The zona pellucida is a sort of specialized extracellular matrix, produced by follicular cells and mostly made by glycoproteins and glycosaminoglycan, which are typical components of the extracellular matrix, but here in the zona pellucida they are very specific and are called zonula proteins 1-4 (ZP 1-4).

How does the embryo implant? IMPLANTATION

There are 3 stages of implantation: 1. apposition 2. adhesion 3. invasion

How do the TORCH cross the placenta?

There are several mechanisms: directly through the trophoblast layer, they can infect the syncytiotrophoblast, they can infect the cytotrophoblast through the maternal microvasculature, they can be transported in a paracellular or transcellular transport and so on. You don't need to remember all these mechanisms, but it is important to know that there are several. Pathways may vary according to the gestational age.

What concept is visualized in this image?

This concept of the dermatome can be visualised in the image above. If you take, for example, a piece of cotton or a pin, and you touch the skin and there is a problem in the sensitivity in the T2 dermatomes, it means that there is something wrong with the T2 segments of the spinal cord. That is why it is important to remember this connection.

Summary of Folding on the horizontal plane or formation of lateral folds in the embryo:

This is complicated, but try to analyze the drawings. First, the amniotic sac grows so much that it starts to push down the region of the lateral plate mesoderm. This forms a cavity within the lateral plate mesoderm, where part of the endoderm of the yolk sac is brought into the future body of the embryo.

What do we see in this diagram in terms of the envelopment of the embryo body by the amniotic sac?

This is shown in the drawing with cross-sections to the right. Cross-section (B) is very rostral, no communication, cavity complete. Cross-section (C) is a bit more caudal at the level of the liver, with no communication, so the intraembryonic coelom is separated from the extraembryonic coelom. In cross-section (D), in the center of the body of the embryo, you see that there is still communication (it's open). The center is still open (communication), while the caudal part of the embryo is closed (no communication). In the center, there is still communication between the intraembryonic coelom and the extraembryonic coelom.

What are the substances exchanged between the maternal blood and the fetus?

This scheme shows the substances exchanged at this level. 1. Water, oxygen, nutrients, hormones and all the other necessary substances are carried by maternal blood to the foetus. 2. Unfortunately also harmful substances can pass: drugs and alcohol, excess of glucose, maybe due to gestational diabetes, that can really damage the heart of the foetus, viruses, metals (strontium) or microorganisms (toxoplasma gondii). 3. This barrier (from mother to fetus and vice versa) is more a membrane than a barrier, because there's a lot of material that goes back and forth, including immunoglobulins. The immune system of the fetus is not mature yet and it will not be even at birth. Therefore, some of these immunoglobulins are good for the fetus since they provide passive protection until the baby develops its fully functional immune system. 4. IgG= immunoglobulin G guarantees passive immunity during the first months of postnatal life.

Why would a gynecologist perform an amniocentesis? What is its significance?

To detect chromosomal abnormalities, CNS abnormalities, abnormalities of the anterior of the anterior abdominal wall (omphalocele), a duodenal or esophageal atresia (reduced canalization of these two hollow organs which can be detected by the presence of alpha fetoprotein), other index of fetal maturity (lectin-to-sphingomyelin ratio) and then we may use the amniotic fluid to detect if there is an erythroblastosis fetalis: red blood cells of the fetus starts to be destroyed within the bloodstream of the fetus, due to the Rh factor; usually this happens because of a contact between the maternal and fetal blood, frequent in the latest stages of pregnancy or in a new pregnancy: the mother develops antibodies against red blood cells without the Rh factor which can cross the placental barrier and act against the red blood cells of the fetus causing damage to the red blood cells within the vascular bed of the fetus (supposing the mother is Rh positive and the fetus is Rh negative).

Lectures 3

Topic: Fertilization and early stages of the embryo development (week-1 and week 2) Learning outcomes 1• Outline the transport of the egg and sperm up to the site of fertilization 2• Explain the different steps of fertilization 3• Explain the mechanisms that prevent polyspermy 4• Explain what is accomplished by the process of fertilization and the characteristics of the zygote 5• Explain the process of cleavage of the zygote and its role 6• Outline the formation of the blastocyst and explain the role of its different components: inner cell mass, trophoblast, zona pellucida, blastocele 7• Explain the difference between developmental potency and developmental fate 8• Outline the transport of the zygote and blastocyst to the uterine cavity 9• Describe the characteristics of the mucosa of the uterus at the end of the endometrial cycle 10• Outline the phases of implantation of the blastocyst in the endometrium (apposition, adhesion, invasion) 11• Summarize the mechanisms that contribute to initial maternal tolerance 12• Describe the decidual reaction 13• Summarize the most important steps of the progressive embedding of the blastocyst in the uterine wall Ao formation of the cytotrophoblast and syncytiotrophoblast Bo formation of the trophoblastic lacune Co formation of the initial uteroplancental circulation • Explain the transformation of the inner cell mass into the embryonic shield (disc): becoming bilaminar • Describe the first molecular and morphological events indicating that the embryo is "taking charge" • Explain the formation of the amniotic cavity, of the primary and secondary yolk sacs and of the extraembryonic mesoderm • Describe the initial development of the uteroplacental circulation • List the normal and abnormal sites of implantation. Clinical drop: ectopic pregnancy • Explain possible causes of early miscarriage PPP Portfolio-related topic: Abnormal vaginal bleeding, Pelvic pain (abdominal Pain)

Lectures 1 and 2

Topic: Introduction to embryology and principles of male and female gametogenesis Learning outcomes: 1. Explain the importance of studying embryology 2. Outline the periods and phases of human embryology 3. Calculate the date of birth 4. Describe the periods of susceptibility to teratogens 5. List the components of male and female genital tract 6. Explain the phases of gametogenesis 7. Formation of primordial germ cells (PGC) and their migration 8. Increase in number of PGM by mitosis 9. Reduction in chromosomal number by meiosis 10. Compare male and female gametogenesis and summarize their differences 11. Explain the origin of teratomas 12. Explain the structural and functional maturation of egg and sperm A. steps of spermatogenesis and spermiogenesis B. maturation and capacitation of spermatozoa C. hormonal regulation of spermatogenesis D. maturation of the oocyte-follicle unit E. hormonal regulation of folliculogenesis Clinical drop: male infertility 1. Compare the differences in the maturation of egg and sperm 2. Explain the events taking place at ovulation Clinical drop: mittelschmerz 1. Explain the formation of the corpus luteum and its role 2. Correlate the ovarian cycle and the uterine cycle and their hormonal regulation PPP portfolio-related topic: Abdominal pain and pelvic pain

What is a dizygotic pregnancy?

Twins that develop from 2 mature ova. Which means: 1. 2 amnions 2. 2 chorions 3. 2 Placentas Placentas and chorions may fuse if blastocysts implant close They can have different sex They are genetically alike as brothers and sisters

What is developmental potency?

Until the 16 cells stage, cells are pluripotent, this is called developmental potency which is the type of cells to which a precursor COULD give rise. A cell taken from a morula can become both an inner mass cell or a trophoblast cell (related to image).

What is the vasa previa?

Vasa previa occurs when the blood vessels of the umbilical cord are above the opening of the cervix of the uterus. This one can cause bleeding, since the vessels are not in the right position, so they can be stressed or compressed, and that can cause problems in the development of the fetus. It can also lead to fetal bradycardia (slow heart rate) due to the scarcity of blood that reaches the fetus.

Dating a pregnancy

We can date pregnancy either counting from the fertilization date or the onset of the last menstrual period. 1. Traditionally, determining the first day of the LMP (last menstrual period) is the first step in establishing the EDD (expected day of delivery). 2. By convention, the EDD is 280 days after the first day of the LMP. Because this practice assumes a regular menstrual cycle of 28 days, with ovulation occurring on the 14th day after the beginning of the menstrual cycle, this practice does not account for inaccurate recall of the LMP, irregularities in cycle length, or variability in the timing of ovulation. 3. Truth is, the best tool to determine exactly the developmental stage of an embryo and the EDD is through using ultrasound. 4. Ultrasound measurement of the embryo or fetus in the first trimester (up to and including 13 6/7 weeks of gestation) is the most accurate method to establish or confirm gestational age.

How do villi form (development of the villi)? Annotate this image: SOL

We can use this image to understand in a better way the development of these structures.

SELF-EVALUATION questions: What is the blastocyst?

When liquid enters the morula and forms a filled cavity it forms the blastocyst, Components of blastocyst= the trophoblast (outermost cells) and the inner cell mass (or embryo blast, inner cells)

What is the medio-lateral patterning of the embryonic disk like when it is still flat?

When the embryo is still flat, there are some factors more concentrated close to the midline, such as Noggin, Nodal and Chordin, which then become less concentrated towards the lateral border of the embryonic disk.

During development from the epiblast there is the formation of:

a cavitation and the cavitation gives rise to a membrane we call amniotic membrane which would delimit an amniotic sac that is related dorsally with respect to the embryo.

Migration of PGCs is

a complex mechanism that requires dynamic rearrangement of the cytoskeleton. The cells move thanks to the creation of new cytoplasmic adhesions through lamellipodia (actin filaments).

When there's a complete detachment of the placenta, the situation is critical. If the baby is mature enough we go for:

a delivery.

This means that, when looking at a pool of spermatogonia in a specific segment of the seminiferous tubule, we would be able to observe

a homogeneity in the stage of maturation.

A coelomic cavity, a true coelom, can form only in animals that have:

a mesoderm because only the mesoderm can give rise to a serosa.

Each somite is divided into:

a sclerotome and, initially, into a dermomyotome which will then be separated into a dermatome and a myotome. 1. The dermis is derived from the dermatomeric compartment of the somite, while the epidermis originates from the ectoderm. 2. From the myotomeric compartment we get most of the skeletal muscles. 3. From the sclerotome compartment we get bones, joints, ecc... 4. The sclerotome undergoes further subdivisions (sclerotome proper = vertebrae and ribs, endotome = dorsal aorta and endothelial cells, arthrotome = vertebral joints and syndetome = tendon). 5. The sclerotome is going to give rise to the meninges (cover the scalp and the vertebral column) that line the vertebral canal. 6. The largest part of the scapula originates from the dermatome. 7. Between the sclerotome and the myotome we can find the syndetome (it derives from dermatome), which gives rise to the tendons of the neck's musculature.

So due to the folding of the embryo, we have:

a single tubular heart.

The amniotic fluid interests us because the composition can be studied. A gynecologist can perform an:

amniocentesis (enter with a needle inside the amniotic sac and sample some amniotic fluid).

What is a teratogen?

an agent or factor that causes malformation of an embryo. A teratogen is an agent, chemical, physical or biological that alters fetal morphology or function if the fetus is exposed to it during a critical stage of development -- because there are periods, where the embryo is more susceptible to teratogens (usually the period of the first few month -- 3 to 8 months).

Interaction between oocyte and follicular cells maintains

arrest of meiosis I in the diplotene stage.

The cytoskeleton of the tail is the

axonema, made of microtubules (in particular, 9 pairs of microtubules disposed in a circle and 1 central pair). Each couplet is made of an A microtubule and a B microtubule.

Where does the mesoderm form?

between endoderm and ectoderm (epiblast), except for the oropharyngeal membrane and cloacal membrane (in those 2 areas the mesoderm doesn't go).

There is a __________ between the oocyte and granulosa cells

bidirectional signaling Have to know the general concept of the diagram.

The basal compartment is more exposed to ____.

blood, since it is in the connective tissue. In blood there are immune cells that can recognize an antigen. We need to keep separated the possible exposure of the immune system to spermatogonia: as spermatogonia enter meiosis I, they change antigenically and they need to migrate in the adluminal compartment, because the immune cells would recognize them as different and would attack them.

Arteries:

bring blood from the heart to the periphery.

Veins:

bring blood from the periphery to the heart

cGMP results in

cGMP (from folllicular cells) Inhibits Phosphodiesterase cAMPè 5'AMP Have to know the general concept of the diagram.

The tail bud is what remains...

caudally of the primitive streak, that has swollen and has transformed. The formation of the neural tube is also called neurulation.

Humans are similar, but not quite the same. If you recall, we said that in the 3rd week, the lateral plate mesoderm starts undergoing a process called:

cavitation.

They may also occur in the

central nervous system (brain or spinal cord), chest, or abdomen. Teratomas may be benign (not cancer) or malignant (cancer).

From the fetus' point of view, the main factors that can cause IUGR:

chromosomal abnormalities that prevent the correct growth of the fetus.

SELF-EVALUATION questions: What is cleavage?

cleavage is cell division without an increase in the size of the whole structure.

Going back to the annelid, it has a true intraembryonic cavity, so is called a:

coelomate

Some very simple animals, such as the flatworm, have a mesoderm, but they don't have a:

coelomic cavity (as you can see from the picture beside).

Not all spermatozoa are

compatible with fertility, even in a normal fertile male, some spermatozoa are abnormal.

Communication between the lacunae and the maternal blood vessels is a _____.

complex system. 1. The capillary network has a pink vessel and a blue vessel, showing the side where blood has more oxygen and nutrients and the side less oxygenated and with less nutrients. 2. At some point the cytotrophoblastic shell starts to invade the spiral artery wall. That is a very important passage. In the previous image we saw that there is blood in the lacunae because the cytotrophoblast has been eroding the wall of spiral arteries, so blood can arrive to the lacunae, but then the cytotrophoblastic shell forms. 3. Now those cells literally invade the wall of the spiral arteries that send blood to the lacunae. Thanks to that, the wall of those vessels as they enter the lacunae changes. 4. It is substituted by cytotrophoblastic cells and this makes it so that the blood flow in these vessels becomes high, but at low pressure. So, they can guarantee a continuous blood flow in the lacunae but with low pressure so the villi are surrounded by blood but are not subjected to high pressure.

If the embryonic disk does not divide completely or 2 adjoining disks fuse (takes place in the level of the morula or the inner cell mass), we have =

conjoined twins.

Development ----

continues after birth.

If fertilization does not take place =

corpus albicans.

As you know, if fertilization and implantation takes place, the corpus luteum transforms into the ______.

corpus luteum gravidicum that produces estrogen and progesterone.

The oocytes and associated follicles mature in the

cortex of the ovary.

The ovary is made by a central part, the medulla and the more peripheral region, the:

cortex of the ovary.

There is another second messenger molecule that accumulates inside the cytoplasm of the oocyte, which is:

cyclic GMP (cGMP), also produced by follicular cells.

Somitogenesis ends around:

day 30 of development.

What are ciliopathies?

defects in structure and function of cilia

The problem in these cases of pathological placenta is at ...

delivery; if the placenta is too much attached to the uterus or even to the myometrium, it is very difficult to detach it without causing severe haemorrhages, difficult to control that may kill the mother. So, this can lead to third trimester bleeding.

The membrane of the head of the spermatozoa becomes antigenically different and is divided into

different antigenic domains (changing during maturation in the male and in the female genital tract)

While PGCs migrate, they come into contact with

different environments (other cells and the extracellular matrix).

Now that we can distinguish 2 layers, we can also start to establish a...

dorso-ventral patterning.

Once the endoderm and the mesoderm are formed, the cells who remained in the epiblast are called:

ectoderm. Some of the cells of the ectoderm will continue their original destination into becoming the epithelial cells that cover the body, while others (the ones above the notochord) will become neuroectodermal cells and give rise to neuroepithelium.

Sometimes the embryo doesn't implant where we want to, causing an:

ectopic pregnancy.

The product of the seminiferous tubules, the semen, is called the

ejaculate.

What is the embryonic adnexa?

embryonic adnexa = the placenta and the extraembryonic membranes.

The placenta is an

endocrine organ.

However, the invasion needs to be limited to the...

endometrium, which is a hollow organ, so it has a mucosa, a less developed submucosa (since it is also a saccular organ) and a very thick muscle layer.

What muscles originate from the epimere?

epaxial muscles of the body originate from the epimere, which are the intrinsic muscles of the back. These originate and insert themselves on the vertebral column.

The maturation of spermatozoa and their acquisition of motility takes place in the

epididymis because the epididymal cells produce a factor called the Factor Motility Protein.

The roundworms have a cavity, but it is not a true coelomic cavity, as it is not:

excavated within the mesoderm, but is in between the mesoderm and the endoderm.

Reduced utero-placental circulation results in _____.

fetal hypoxia and intrauterine growth restriction (IUGR). It can be because the placenta did not develop correctly or because there may be a partial detachment of the placenta.

Difference between filopodia and lamellipodia:

filopodia are tiny and elongated while lamellipodia are more flat.

Spermatozoa are propelled in the epididymis by

fluid pressure generated in seminiferous tubules and by muscle contraction and ciliary movements

Gastrulation is a very critical event that will finally give rise to the:

formation of all the tissues of the embryo (3 germ layers = ectoderm, endoderm & mesoderm) and therefore to all the organs: it needs to be very tightly controlled.

What is angiogenesis?

formation of new blood vessels from existing vessels (in the adult, eg. during menstrual cycle, wound healing, tumours).

What is neurolation?

formation of the neural crest.

Dorsal aortae

from which the veins originate including the intersegmental arteries that are distributed to the body of the embryo. The circulation is symmetrical, obviously it changes a lot during development.

Maturation of follicles is divided into a...

gonadotropin-independent phase and a gonadotropin-dependent phase Gonadotropins (aka. gonadotropic hormones) are LH and FSH (act on the gonad)

Envelopment of the body of the embryo by the amniotic sac is incomplete in:

incomplete in the umbilical region where communication between the extrambryonic coelom and intraembryonic coelom will persist for a time.

A video about "Plane Folding" is shown:

http://www.youtube.com/watch?v=qMnpxP6EeIY During the "Transverse Plane Folding" section, the professor commented: These are the lateral folds. The amniotic sac slides on the sides of the embryo and starts to enclose part of the yolk sac within the body of the embryo. In the central region of the embryo, there is still communication between the intraembryonic and the extraembryonic coeloms, while in the most rostral and caudal regions of the embryo the communication disappears. So, you see no communication. For "Sagittal Plane Folding," the professor commented: Now the video will show you the rostral and caudal folding of the embryo along the sagittal plane.

The maturation of the spermatozoa and the activity of certain cells is under hormonal control from the:

hypophysis (pituitary gland).

After the beginning of meiosis, developing sperm cells become

immunologically different from the rest of the body.

While the amnion, the yolk sac, the allantois, the extraembryonic mesoderm originate from the:

inner cell mass. So when we consider these extraembryonic adnexa and membranes they originate partly from the trophoblast and partly from the inner cell mass.

While they migrate cells

interact with other cells and with substrates in the extracellular matrix. Figure 1. Cell adhesion on a 2D substrate and actin-based motility structures. (a) Schematic representation of a cell attached on a substrate. Actin filaments are the basic structural component found in a number of cellular structures used for cell motility and substrate sensing (insets: filopodium, lamellipodium and lamellum). Certain structures appear sheet-like (e.g. lamellipodia/lamellae, ruffles), whereas others are finger-like (e.g. filopodia). The cell migrates upwards and could be attached to a second cell on the right through cell-cell junctional proteins involving cadherins..

Blockage of uterine tubes

is a major cause of infertility in women Caused by: Infection, inflammation, endometriosis

The intraembryonic coelom is formed in the _____ that splits into ______.

lateral plate mesoderm that splits into 2 sides; one remains on the side of the amniotic sac, and the other on the side of the yolk sac. These can also be called splanchnic mesoderm and somatic mesoderm.

To review, we talked about the intraembryonic coelom during gastrulation, when we were mentioning a few things about the:

lateral plate mesoderm.

DEVELOPMENT is a

life-long process that includes also aging and senescence (driven by biological clocks). We are not able to identify when development stops. Senescence (process of aging which is guided by cellular mechanisms = biological event -- proof of senescence is that it can be very much accelerated --because of an event that causes the mutation of a gene = body ages much more quickly than it should) may take place earlier than it should... ONE SMALL MISTAKE..... is enough to lead to accelerated aging process. Mutation of gene LMNA: lamins, main components of nuclear lamina. The individual is subjected to Hutchinson Gilford progeria syndrome.

Sertoli cells are important because they

maintain the blood-testis barrier and contribute to the isolation of the antigenically different haploid germ cells from the male adult immune system. ***Haploid because while meiosis is proceeding, the genetic material is halved.

IUGR can be due to:

maternal factors, foetal factors, placental and cord abnormalities or because of infections.

Spermatozoa further _____

mature and and acquire motility in the epididymis (12 days) and are stored in its lower part.

Teratomas may be

mature or immature, based on how normal the cells look under a microscope. Sometimes teratomas are a mix of mature and immature cells.

What is crown-rump length?

measurement of foetus from top of the head to bottom of bum.

As there are factors that contribute to the rostrocaudal patterning of the embryonic disk, there are also factors that contribute to the:

medio-lateral patterning of the embryonic disk; For example, the intraembryonic mesoderm organizes from medial to lateral within the notochord, the paraxial mesoderm, the intermediate mesoderm and the lateral plate mesoderm.

The ovary is made by a central part, the:

medulla

Spermiogenesis takes places after

meiosis II

Organs are suspended in the coelomatic/serosal cavity by:

mesenteries.

The paraxial mesoderm is made by:

mesoderm mesenchyme: when the somites are formed, the mesenchyme undergoes a mesenchymal to epithelial transition.

Sometimes PGCs do not

migrate correctly either in the gonad itself or they follow other routes. Anomalies in the movement of PGCs can cause teratomas.

After the beginning of meiosis developing sperm cells become immunologically different from the rest of body (non-self = a immune-response against them is formed = bad), which leads to

migration to the adluminal compartment. Need for an immunosuppressive environment (= makes it so there is no contact with the basal compartment = cells in the basal compartment).

CAPACITATION REACTION exposes...

molecules that are able to bind to the zona pellucida of the ooctye

segmentation also affects the region of the ...

neural tube which is closer to the somite (so the future spinal cord).

The prechordal plate and notochord are very important for the induction and patterning of the:

neuroplate. (FORMATION OF THE NEUROPLATE) Dorsal to the notochord cells of the embryonic ectoderm become a neuroepithelium. 1. Some cells between the ectoderm and the prechordal plate will form the neural crest (believed to be a 4th layer). 2. The neuroectodermal cells already know their final destination (in the brain or in the spinal cord) and what type of cell they are going to become (astrocyte, neuron and so on).

Complete mole:

no fetal tissue, 2% risk of ch0riocarcinoma

up to more or less the 20th week of gestation, the skin of the fetus is...

not keratinized and therefore there is a balance between the composition of the fluids of the embryo and of the amniotic fluid. No keratinization → passage. The purpose of having a keratinized skin is because it acts as a barrier.

At the end of spermiogenesis and spermiation, when the mature spermatids/spermatozoa are released into the lumen, it is important to highlight that at this point mature spermatids/spermatozoa are:

not motile yet and cannot fertilize anything.

Explain the structural and functional maturation of egg:

o maturation of the oocyte-follicle unit o hormonal regulation of folliculogenesis (A) OOGONIA this first stage occurs within the fetus of the developing female, primordial germ cells division to multiply to form numerous small oogonia. (1) Primary Oocytes ● at the fifth month of pregnancy of the forming female fetus, the oogonia undergo the first stage of meiotic division to form oocytes. Meiotic division will then cease, until the female fetus, is born and reaches puberty. Upon reaching puberty, in each menstrual cycle, a few oocyte follicles will develop, one of these cells will develop into Graafian follicle to release an ova during ovulation. Note: only a fraction of the primary Oocytes survives to puberty, and even fewer will be released over the lifespan of the female reproductive years. (2) Graafian follicle ● mature follicle containing the primary oocyte which is released during ovulation. The first meiotic division is completed producing a secondary oocyte and first polar body. (B) SECONDARY OOCYTE ● final stage of first meiotic division, where a viable oocyte is produced ready for fertilization, with a lesser polar body being an unusable portion of meiotic division products. (C) DEFINITIVE OVUM ● (mature ovum) production of final female haploid cell, with 23 chromosomes ready for combination with the male haploid cell and recombinant reproduction. (D) POLAR BODY ● small cells of unusable meiotic division products. Polar body products can be produced at the end of the first meiotic division, and additionally at the end of the second meiotic division. These bodies will be reabsorbed products.

Explain the structural and functional maturation of sperm:

o steps of spermatogenesis and spermiogenesis o maturation and capacitation of spermatozoa o hormonal regulation of spermatogenesis

Bleeding from a placenta abruption can be:

obvious (external bleeding), but also internal bleeding, which can be worse, as the mother can be feeling fine, but doesn't know that this occured.

So that leaves us with:

one endocardial tube which is the heart surrounded by the portion of the intraembryonic coelom that we call the pericardial cavity.

The pericardial cavities that were developing (one on the right and left), because of the folding of the embryo, come together and form:

one single pericardial cavity (serosa cavity) that surrounds the single tubular heart.

Teratomas usually occur in the

ovaries in women, the testicles in men, and the tailbone in children (sacrococcygeal teratomas).

Another domain of the mesoderm is the...

paraxial mesoderm.

The mesoderm is divided by the coelomic cavity, with a _____ and a ______.

parietal layer and a visceral layer. This will take the name of somatopleure and splanchnopleure, respectively.

Let's suppose that a pregnant woman is driving a car and that she has an accident which causes a movement of the organs in her body. They keep on moving until they are blocked by the body wall. Here you can go through a:

placenta abruption, a premature separation (partial or complete) of the placenta from the uterine wall.

IUGR comprises a:

poor development of the fetus.

If this transformation of maternal blood vessels doesn't take place correctly, there is a _____.

poor placental perfusion, which can be the cause of intrauterine growth restriction of the fetus, because the amount of blood and the exchanges are not correct. It can also lead to preeclampsia: it is a condition in which the mother becomes severely hypertensive (high blood pressure, headache, nausea, vomiting) due to the lack of changes in the maternal blood vessels.

Spermatids undergo

postmeiotic changes in sperm morphology. Spermatids need to acquire a certain shape in order to become proper spermatozoa (they need a fluid-dynamic shape, arrow-shape). During maturation spermatogonia lose a lot of cytoplasm and develop a tail.

SECONDARY FOLLICLES become

preantral and antral follicles.

Muscles of the limb derive from____.

precursors that migrate from the myotome.

Most activity of SH- signaling pathways takes place at the level of the...

primary cilium.

Here is a histological image that shows this:

primary follicle.

While the notochord elongates, the primitive streak ...

regresses.

Remnants of the primitive streak can also give rise to:

sacrococcygeal teratomas: most common tumor of childhood become malignant in infancy needs to be removed by age 6 months.

We have the formation of two vertebrae from each ____.

sclerotome.

The diaphragm originates from:

septum transversum, mesentery of esophagus (mesenteries are reabsorbed but when that happens to the one of the esophagus it enters into the composition of the diaphragm), pleuroperitoneal folds and membranes (when the lungs start to develop they excavate into the body wall and create a sort of flap of mesoderm and enter into the composition of the diaphragm), muscular ingrowth from body wall (from the muscle layer of the body wall there are some cells that grow in the diaphragm and contribute to its peripheral portion).

Rostral region of the embryonic disk: the most rostral structure is the:

septum transversum, which is the condensation of the mesoderm.

The delimitation of the intraembryonic coelom by folding is important because the intraembryonic coelom is the forerunner of the body cavities lined by a:

serosa; Most of our body cavities are lined by a serosa, a sliding surface or membrane that produces a tiny layer of fluid (examples are the pleura that surrounds the lungs, the pericardium that surrounds the heart, and the peritoneum that is inside the abdominal cavity).

Teratomas are a type of germ cell tumor that may contain

several different types of tissue, such as hair, muscle, and bone.

What matures inside the ovary is not only the oogonia but it's also the

somatic and support cells that surround the oogonia/future oocyte to form a very complex unit which is the ovarian follicle.

Partial mole:

some fetal tissue, choriocarcinoma rare

Mesenteries are formed by the ____

splanchnic mesoderm.

Because cells are linked by bridges, in a certain segment of the tubule the same association of cells is visible:

stage

MEIOSIS in females is not only a question of redistributing genetic material but also

storing material for the first needs.

Up to now, the embryo has been:

symmetrical from the morphological point of view; If the situation had remained like that, we wouldn't have had the body as we know it. When observing the adult body we can see that some organs aren't located in a symmetrical way.

Why is the period between the 3 and 8 months most dangerous for the embryo?

teratogens can affect the development of organs, since this is when proper organogenesis happens (all the systems are really coming in to be).

The embryo can be affected by

teratogens.

The process of maturation of the spermatozoa goes from ___

the BASAL COMPARTMENT to the ADLUMINAL COMPARTMENT

Segmentation takes place in...

the PARAXIAL MESODERM of the TRUNK region

Breaking of the waters means that...

the amniochorionic membrane breaks.

If this change doesn't take place, so if the invasion in the cytotrophoblastic cells into the last part of the spiral arteries doesn't take place, then ______.

the blood flow of the placenta will not work correctly and this can cause intrauterine growth retardation. Fetal blood has a lower concentration of oxygen and a lower pO2 than maternal blood. So fetal hemoglobin must have a higher affinity for oxygen than maternal one. That is the reason why fetal hemoglobin is different from the adult one. There is less oxygen in the fetal bed with respect to the maternal bed, so a higher affinity is needed.

The lateral plate mesoderm will line:

the body cavities.

What can you see in this image? (SOL)

the chorionic cavity, the amniotic cavity and the fetus grow so much that the lumen of the uterus is completely filled and disappears. So, the decidua capsularis disappears and we come to the point where the wall of the chorionic cavity, without the interposition of the decidua capsularis, fuses with the decidua parietalis. The amnion and the smooth chorion (chorionic leave) fuse together to form the amniochorionic membrane.

During ovulation, the theca externa, theca interna and some granulosa remain within the ovary and give rise to a very important structure:

the corpus luteum("luteum" because of its yellowish colour).

Where do the craniofacial bones originate?

the craniofacial bones originate from the mesoderm of the head and the neural crest cells.

The zona pellucida will be very important in the future both for

the destiny of spermatozoa that reach the oocyte as well as for the initial development of the embryo. The oocyte and the follicular cells keep on communicating across the zona pellucida. For example, microvilli of follicular cells extend to the zona pellucida and through the gap junction they communicate again with the oocyte, otherwise it would not keep the oocyte with the right amount of secreting second messengers.

HATCHING OF THE BLASTOCYST AND EARLY IMPLANTATION: How does the blastocyst hatch and implant? In this image we see...

the embryo moving out of the zona pellucida (pink) = it is like a chicken hatching from egg.

What about the immunotolerance of the embryo?

the fetus is a semi-allograft = it is a foreign tissue from the same species with a different genetic makeup. The zona pellucida is not there any longer, hence the regulation of immunotolerance is important. Involvement of cytokines (from endometrium. e.g. Leukemia inhibiting factor ) and their receptors (on trophoblast) Leukocytes that have infiltrated the endometrium on the last phase of the cycle produce interleukin 2 that prevents recognition of the embryo as a foreign body.

in reptiles the yolk sac has many nutrients to allow growth inside it and then at some point hatch. This is not required for humans because

the fetus is connected to the placenta. Still there are some substances in the yolk sac that at the beginning give a bit of nutrients and vitamins to the embryo by absorption through tissue (endocytosis). This type of nutrition is called histiotrophic nutrition, because it contributes to the tropism of the tissue.

The fetus needs the amniotic fluid not only to practice the musculoskeletal movement, for protection against adhesion, for the homeostasis but also because...

the fetus swallows the amniotic fluid and this is very important for the development of the digestive system and the respiratory system.

The intermediate mesoderm is going to give rise to:

the gonads, the kidneys, the urinary system and part of the genital system.

When does the heart start to beat during this fourth week period?

the heart starts to beat around the 21st-22nd day and can be heard by Doppler ultrasonography during the fifth week (7th week if we consider the last known menstrual period).

The formation of the placenta occurs through:

the invasion of the blastocyst into the wall of the uterus is, for instance, an invasive process, which is mainly led by the syncytiotrophoblast.

Where do the limb bones originate?

the limb bones originate from the lateral plate mesoderm

Spermatogenesis represents

the maturation of spermatogonia to spermatids. It takes place in the seminiferous tubules of the testis.

We said that the placenta is not really a barrier because it allows...

the passage of both materials that are needed and some harmful substances, including infectious diseases. So, it is not a full proof system. The fetus can be infected by microorganisms in different ways: first of all through the placenta, but also during the passage through the birth canal. The neck of the uterus is not sterile, so if there is an infection at the birth canal (such as an herpes), it can affect the baby at the moment of birth.

It is important to understand that at this point the circulation of the mother is connected to:

the placenta and to the circulation of the fetus, so the peripheral resistance of the vascular bed of the mother includes the placenta. So if those vessels don't transform correctly, it also changes the way the peripheral resistances are in the maternal circulation.

An example of placental and cord abnormalities is:

the placental insufficiency; the placenta develops, but not with the right surface or thickness, so it's insufficient and there's a reduced delivery of substances. Sometimes it can happen that there is just one umbilical artery, so the blood vessels that keep the communication between the placenta and the fetus don't develop in the right number.

The median folds are

the rostral and caudal folds, which can also be called the head and tail folds respectively.

What is a spermatogenic wave?

the sequential ordering of stages along the length of the seminiferous tubule. The distance along the tubule between the same stage is called a spermatogenic wave The length of the segment in which I can observe the same stage of maturation along the seminiferous tubule is defined as a wave.

Another region that reminds us of this segmentation is:

the spinal cord which is not divided physically like the vertebrae but functionally speaking has a segmental organization. The boundaries between one segment and another is determined by the roots of the spinal nerves.

There are several pathways by which Zika virus (ZIKV) can cross the placenta and reach the fetus. However, this pathogen is not the only one:

they are complessively called TORCH (Toxoplasma gondii, Other, Rubella virus, Cytomegalovirus (CMV), Herpes simplex virus (HSV)).

The cytotrophoblastic cells must have some invasive properties for their function but these invasive and proliferative properties may sometimes become problematic, because _______.

they can lead to gestational trophoblastic neoplasia ( these cells in the process of forming the shell, can proliferate to much forming a neoplasia, neoformation of tissue) and choriocarcinoma which is a malignant tumor of the chorion due to excessive proliferation and invasion of cytotrophoblast cells.

What is the zona pellucida?

thick outer covering of human egg cell. penetrated by sperm acrosome

To have an intraembryonic coelomic cavity we must be a:

triploblastic animal (have 3 layers); Most triploblastic animals have a fluid-filled space somewhere between the body wall and the gut. Such a cavity can provide numerous functional advantages.

When we talk about these structure must specify that the placenta and chorion develop embryologically speaking from the:

trophoblast - the outer layer of the blastocyst.

The annelids do have a:

true coelomic cavity (the space in between the two yellow parts which are the mesoderm).

Angiogenesis can take place also in ______.

tumors; tumors start growing so much they start being hypoxic and to keep growing start producing substances which attract new blood vessels. An interesting phenomenon (in some breast tumors) is called vasculogenic mimicry: tumor cells organise themselves to form small vessels which can be crossed by red blood cells.

The placental is connected to the embryo by the...

umbilical cord.

Finally they will come together to form the:

umbilical cord; so the mesenchyme present in both of these structures comes together into forming a single structure.

umbilical circulation

umbilical veins and umbilical artery.

Hydatiform mole may presents with...

vaginal bleeding, uterine enlargement more than expected, pelvic pressure/pain, excessive production of hCG (hyperthyroidism, hyperemesis = very acute nausea and vomiting)

Also the initial part of gastrulation is...

very critical: mother can have some behaviors that are going to affect the embryo, but she might not know she's pregnant -- vulnerable to teratogens.

The yolk sac in humans is a:

vestigial organ (vestigial function).

Learning outcomes: At the end of this lecture, students should be able to:

•Outline the importance of gastrulation •Define the role of primitive streak and primitive node and the formation of the body axes •Outline the steps that characterize gastrulation. Clinical drop: epithelio-mesenchymal transition •List the derivatives of the endodermal layer •List the different compartments of the mesodermal layer and their derivatives •Outline the stages of formation of the notochord. Clinical drop: chordomas •Describe the steps that lead to the formation of the neural plate and neural tube including secondary neurulation •List the derivatives of the neural crest. •Developmental defects: sirenomielia; ethanol as a teratogen (holoprosencephaly); Shh signaling pathways and the primary cilium •Explain the mechanism/s of breaking down of the symmetry of the embryo. Developmental defects: situs inversus and Kartagener syndrome •Summarize some basic molecular events involved in the rostrocaudal and mediolateral patterning of the embryo. PPP Portfolio-related topic: Headache

During the first week, how does the embryo eliminate wastes? And what about the second week?

→ During the first week the embryo eliminates wastes and receives nutrients by diffusion, but during the second week an uteroplacental circulation is established between the future fetus and mother.

Example of the Repression of epithelial features:

→ For example Snail is a transcription factor called zinc finger transcription factor because it has a zinc molecule embedded in its overall structure. → This is a piece of a gene that codes for e-cadherin, which is a molecule typical of the junctions of the epithelial cells. → We want to repress the expression of e-cadherin: Snail and others bind to the DNA in the region that promotes the production of e-cadherin repressing its production.

When does most of gastrulation take place?

→ Most gastrulation takes place during the third week, but the last part of it actually takes place during the beginning of the 4th week → There are some events that can disrupt gastrulation also during the fourth week because it's still taking place in the caudal part of the embryonic disc.

During the second week an uteroplacental circulation is established between the future fetus and mother. How does this function?

→ Mother through her bloodstream brings into the lacunae of the syncytiotrophoblast water, carbohydrates, vitamins, hormones, electrolytes, oxygen or other nutrients, then passing the barrier between the capillaries and the maternal lacunae there'll be the passage of these substances to the embryo. → All the wastes that the embryo produces are eliminated through the maternal body because they cross the barrier and reach the maternal blood. → The fetal kidneys do not eliminate wastes because there is the placenta, but they produce a type of urine different from ours that contributes to the amniotic fluid. → The carbon dioxide produced by the fetus (the fetus doesn't breathe so there's no exchange with the outer environment) passes through the maternal blood and is exchanged with oxygen.

What factors is snail under control of?

→ Snail is under the control of many other factors such as FGF (fibroblast growth factor), Wnt (signalling factor), BMP (morphogenetic protein), TGF-beta (tumor growth factor beta), parathyroid hormone peptide receptors... → Snail for example represses e-cadherin, desmoplakin and cytokeratin-18, but also induces the production of vimentin inside the cytoskeleton (important because it's typical of immature epithelial cells) → Epithelial-mesenchymal transition is a mechanism that can take place also in adult tissue, but this is a problem: cells that are supposed to remain undifferentiated start to undergo EMT, sometimes erode the basal membrane of the epithelium and from there they start to go around. → when processes typical of embryogenesis are reactivated during adult life they can lead to cancerogenesis if they're not under control.

14-15 days of development:

→ The chorionic cavity has become very large → In blue amniotic sac, in yellow vitelline/yolk sac → The complex made by the bilaminar embryo, the amniotic sac (dorsal) the vitelline sac (ventral) is suspended in the chorionic cavity through a peduncle of mesodermal tissue which is called the body stalk or connective stalk. → the situation of the syncytiotrophoblast and of the cytotrophoblast is changing: spiky protrusions of the cytotrophoblast covered by the syncytiotrophoblast are visible, which are the primary villi. (beginning of the placenta with the formation of the villi)

How can this exchange of maternal blood also be problematic?

→ The problem is that also harmful substances may pass: for example some pathologies from which the mother is affected (rubella, cytomegalovirus, toxoplasma gondii..) may reach the embryo and also some drugs or alcohol.

The mesodermal mesenchymal cells organize themselves in a very complex way, how?

→ They take different pathways of migration: some remain close to the midline, some migrate very rostral, some migrate to the side.. → There are 2 exceptions: 2 places in which the endoderm and the future ectoderm are really attached, with no mesoderm in between: very thin areas → One of them is rostral and is called the oropharyngeal membrane, the other one is caudal and is called the cloacal membrane: at the level of the oropharyngeal membrane there'll be the development of the oral cavity; where there is the cloacal membrane there'll be the opening of the digestive system and of the uro-genital system, so communication with the outside (that for the fetus is the amniotic sac)

image A vs image B:

→ looking at the core of the villus: 1. in A it was just the cytotrophoblast covered by the syncytiotrophoblast 2. in B, within the cytotrophoblast, there's an invasion of some mesodermal cells: this is a secondary villus

What is Sirenomelia?

→ sirenomelia: the last part of gastrulation doesn't proceed as it should, which causes a severe defect in the development of the lower limbs which remain just one single limb (even if there are different degrees). → It's not just the somatic part of the body which is affected but there are also severe defects in the development of the last portion of the digestive tract, of the urinary system and of the genital tract.

What is situs inversus?

→ situs inversus (typically totalis): everything in the body is mirrored. Usually it's clinically irrelevant, but sometimes the situs inversus totalis is associated with Karagener syndrome (bronchitis, sinusitis, infertility..)

looking at the outside:

→ the syncytiotrophoblast has lacunae and is very erosive: it has reached the vessels that are in the endometrium, eroded them and now the maternal blood flows into the lacunae → the content of the maternal glands in the endometrium goes into the lacunae as well: in the last phase of the uterine cycle the glands of the uterus become very long and are rich in their lumen of material that can be nourishing for the embryo. → Since there are no blood vessels in the embryo, everything takes place at this moment by diffusion, which is still enough to sustain such a small and thin embryo. It will be enough for a short time: while all of this is taking place, the embryo and the tissue surrounding it will start to develop their own blood vessels to be able to connect with the maternal blood vessels and to be able to continue to sustain the embryo.

Later in day 13 of development:

→ there is a second wave of proliferation of mesodermal cells that causes a constriction of the yolk/vitelline sac: part of it is eliminated (then it disappears) → the part that is on the side of the embryo remains and is the definitive yolk sac or secondary yolk sac.

Because of the appearance of the primitive streak there's the determination of a lot of the body axes of the embryo:

→ we could already distinguish dorsal and ventral because of the presence of the epiblast and the hypoblast: dorsal is where the primitive streak appears, so on the side of the amniotic sac and of the epiblast. → there is a cranial or rostral and caudal component: the cranial or rostral part of the embryonic disc is where there is no primitive streak (it's not everywhere along the midline but just on one half), while the caudal is the part in which the primitive streak appears. → now that the streak is in the middle, there's a right and left side of the embryo, there is a laterality: we can say medial and lateral with respect to the streak.