Embryology Primers: Placenta, Endoderm (card 40), Lung (card 60)
What is the decidual reaction? (day 9)
The inflammatory response of the epithelium to being invaded by the embryo. The decidua begins to grow around the embryo.
What is the Os?
The lumen of the uterus
Greater and Lesser Omentum
The organs at this stage hang within the Intraembryonic Coelom. Here the Dorsal Mesogastrium is labeled the Dorsal mesentary B) Follow the purple arrow. The entire structure rotates Clockwise as the liver bud grows NOTE the formation of the Greater Omentum (Sac) from the Dorsal Mesogastrium. It dangles From the stomach. C) Rotation of liver is complete Note the formation of the lesser Sac as the liver grows in size.
Umbilical Cord Abnormalities
Umbilical Chord Abnormalities 1. Chord can wrap around neck causing difficulties 2. False Knots can cause decreased blood flow a. Cardiac and vascular defects
What is erythrocyte mosaicism
When chorions fuse in dizygotic twins, it is possible for babies to have an A and O blood type due to dad and mom bloods being different
Does each region of the gut tube have its own blood supply?
Yes, the three regions are the *foregut/celiac artery*, *Midgut/Superior Mesenteric Artery*, and *hindgut/Inferior Mesenteric artery*
Oligohydraminos
a. Results from decreased amounts of amniotic fluid i. Can cause lung and G.I. Deformities. 1. Can see this with ultrasound
Where and what is the cytotrophoblast shell?
forms the borders around the developing blood vessels (see picture)
What lines the yolk sac?
hypoblast (primitive endoderm)
What is the relationship between the mesoderm and the gut endoderm
mesoderm holds the gut organs in place and forms the structure that holds the gut tube *peritoneal cavity* The *splanchnic mesoderm* pushes together and so does the *intermediate mesoderm* which ultimately forms the structure that holds the gut tube in place.
Where do the lungs develop from
pharyngeal arch region
Accessory Organs derived from gut tube endoderm
pharyngeal pouch, lungs, liver parenchyma, hepatic duct epithelium, gallbladder, cystic duct, common bile duct, dorsal and ventral pancreas, urogenital sinus and derivatives
Respiratory diverticulum gives rise to what
the lungs. It is a bud of endoderm coming off the pharyngeal arch region way in the back of the throat
Which cells release metalloproteases?
trophectoblasts invade the uterine epithelium releasing metalloproteases. Upon reaching the decidua they differentiate into syncytiotrophoblasts (syncytium is a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei.
Is the hypoblast at the visceral End?
yes
What happens to the decidua parietalis, chorion laeve, and amnion at end of month 3 (15-17 weeks)
*All of these three membranes have fused on the opposite side of the chorionic frondosum* *EMBRYO IS STILL TECHNICALLY INSIDE THE DECIDUEM*
Growth of Placenta >21 Days
*Chorion frondosum* - functional portion of the chorion *Chorion Laeve* - tertiary villi that eventually disappears
Organs from hindgut
*Distal 1/3 of Transverse colon, descending colon, sigmoid colon* Left one third of transverse colon Descending colon Sigmoid colon rectum
Organs from foregut
*Esophagus , Stomach, liver, gallbladder, pancreas, upper duodenum* Pharynx Thoracic esophagus abdominal esophagus Stomach Proximal half of duodenum (superior to ampulla of pancreatic duct)
IUGRs
*Fetal demise (morbidity) Perinatal distress Low birth weight (smoking) Perinatal asphyxia (low or lack of oxygen to fetus) Cognitive abnormalities Cerebral palsy Cardiac anomalies (valve disorders)*
Organs from midgut
*Lower duodenum, small intestine, ascending colon, proximal 2/3 of Transverse colon* Distal half of duodenum jejunum ileum cecum appendix ascending colon right two thirds of transverse colon
How do Blood Vessels form in the Embryo
*Occures first* in definitive yolk sac but then quickly proceeds to extraembryonic mesoderm A. EXM covers the endoderm of secondary yolk sac B. Mesoderm cells begin clustering and differentiating into hemangioblasts C. Further differentiation of hemangioblasts produce *both the primitive blood cells and endothelial cells lining capillaries*
How does Mom's blood get into the chorionic frondosum with low blood pressure
*the Placental Septua* blood bounces off the septa and is able to bathe the tertiary villi. Septa invaginate so the blood can fully bathe the villi.
Pre-eclampsia
-A syndrome recognized by shallow implantation -Occurs in 5% of all pregnancies -20% of all serious birth complications -especially in first preg. -overweight women -IVF with donor egg -Cause is not really known (*until a couple of years ago*) -can be genetic predisposition -Creates problems in both mother and fetus Mother: throughout pregnancy (mostly seen in 3rd trimester) 1. Hypertension-can be very serious 2. Proteinuria 3. Liver inflammation 4. Edema 5. clot-plugging platelets depleted 6. Severe cases lead to swelling in the brain, convulsions and possibly coma. At that point the syndrome is termed Eclampsia Fetus: 1. Usually results in premature birth
Plancental Abnormalities
-Placenta Accreta: Lack of decidua basalis -Placenta Percreta: Villi penetrate myometrium -Cotyledon malformation *all can lead to intrauterine growth restrictions (IUGRs)*
How is the Stomach Formed
-The stomach forms in the foregut -A-C are viewed from the front (ventral) of the body. -Note each mesentary and vagal nerve branches Within 10 days the posterior region of the stomach expands -At day 35 or so, the stomach rotates clockwise on its long axis. NOTE: the region of dorsal mesentary that holds the stomach is known as the *Dorsal Mesogastrium*
Purpose of Terminal Sac Stage
1. 2-4 weeks before birth Another population of Endothelial cells differentiate into Type 2 Alveolar Epithelial cells. These endothelial cells remain cuboidal or become pseudostratified. Main Purpose is to produce and secrete phospholipid-rich fluids known as SURFACTANTS. Main Purpose of *Surfactant* is to coat the entire terminal alveolar sac and lower surface tension at the air-alveolar interface. Without Surfactant the baby will undergo severe breathing problems. Known genes involved in making Surfactant TTF-1 HNF-3 Glucocorticoids Thyroxine Surfactant A/B
Congenital Lung Cysts
1. Form as larger bronchioles are dilated during development. 2. Can be large. a. Viewed by radiography can give lungs a honeycombed appearance. b. Drain poorly and can result in chronic infections after birth.
Oligohydramnios (again)
1. Occurs from insufficient amniotic fluids in contact with lung tissues. Areas of lung where little or no amniotic fluid bathed them are underdeveloped.
Buds of the Bronchioles
1. Once the Secondary buds are well formed they are anatomically known as secondary bronchioles 2.Secondary bronchioles divide dichotomously forming 10 tertiary bronchi on the right lung and 8 in the left.
Canalicular Period
16-26 Weeks, Each terminal bronchiole divides into 2 or more respiratory bronchioles, which in turn dived into 3-6 alveolar ducts. Purpose of Canalicular Stage Week 16/17-26/27 1. Tertiary bronchioles grow, divide and differentiate into Respiratory bronchi. They grow further within surrounding mesoderm 2. Some Resp. bronchi can differentiate into terminal alveolar sacs capable of gas exchange 3. By 5.5-6 months vascularization of lungs is well underway. Some alveolar sacs come into close contact with fetal blood and in some circumstances by 5.5 months the lungs may support the baby outside of womb.
Terminal Sac Period
26 weeks - birth: Terminal sacs (primitive alveoli) form, and capillaries establish close contact. Purpose of Terminal Sac Stage Week 26/27-Birth 1. To firmly establish blood-air barrier a. Endothelial Cells at Terminal Alveolar Sacs *change their cell adhesion proteins like adhesion jucntions*. These changes allow the cuboidal endothelial cells to flatten. i. These new cells are known as Type 1 Alveolar Epithelial cells. ii. Their flattened phenotype allow intimate association with capillaries. Creates a large surface area for gas exchange
What are the names of the blood vessels that approach and leave the growing embryo
4-5 Weeks Spiral Arteries and endometrial veins Week 4-5 Spiral Arteries supply oxygen and nutrient rich maternal blood Endometrial veins remove wastes and deoxy blood Blood flow approaches 500mls/min by week 18
Pseudoglandular period
5-16 Weeks Branching has continued to form terminal bronchioles. no respiratory bronchioles or alveoli are present. Purpose of Pseudoglandular Stage Week 5-16/17 1. To grow and expand terminal bronchi into surrounding mesoderm 2. The Mesoderm overlying the endoderm of the lungs becomes the Visceral Pleura while the Parietal Pleura overlies the body cavity.
Alveolar period
8 months - childhood: mature alveoli have well-developed epithelial endothelial (capillary) contacts. Purpose of Alveolar Stage *8 months-10 years*. 1. To Provide complete adaptation from aqueous/placental dependence of gas exchange to terrestrial environment. i. Three adaptations must occur. a. Surfactant production b. Proper differentiation of endothelial cells into epithelial cells capable of gas exchange c. Establishment of pulmonary and systemic circulations ii. Alveoli form up to age 10 iii. 17 generations of of budding division occur by month 6 which shows final shape of lungs. iv. An additional 6-7 divisions occur postnatally
What are the functions of the Amnion
A. Comprised of epithelial cells (from epiblast and mesoderm) a few layers thick and is the inner most fetal membrane 1. Fluid a. Composed of water from maternal blood that diffuses through intervillus spaces and *fetal urine*. Other components include electrolytes, proteins, lipids, carbohydrates, desquamated fetal epithelial cells. b. Entire volume is replaced every 3 hrs. c. By 37 weeks the amniotic sac contains 800-1000mls of fluid d. Functions to cushion the embryo from impacts, maintains consistent temp., acts as barrier to infections, and allows a consistent environment. e. *Also functions to bathe the external areas within the embryo (e.g., lungs, G.I. Tract) amniotic fluid is INSIDE the lungs and GI tract*.
Functions of the placenta
A. Transport 1. Gases O2, CO2, CO 2. Water, Glucose, Vitamins, lipids 3. Hormones a. hCG (feeds back on the corpus luteum), Corticosteroids (from mom) 4. Electrolytes (NaCl, CaCl2, MgCl, etc.) 5. Maternal antibodies a. Selective uptake of IgGs (through a neonatal Fc receptor) Simister NE, Story CM, Chen HL, Hunt JS. An IgG-transporting Fc receptor expressed in the syncytiotrophoblast of human placenta. Eur J Immunol. 1996 Jul;26(7):1527-31. b. Sets up Passive Immunity against diptheria, smallpox, measles, but not chicken pox (vericella zoster), and whooping cough (pertussis). *not chicken pox* 6. Drugs and their metabolites 7. Waste products. Barrier 1. Cutoff around 100,000 Daltons a. excludes most viruses and bacteria. *Zika can penetrate and affect the fetus.* http://www.cdc.gov/mmwr/volumes/65/wr/mm6506e1.htm What about Cells (yes but not common) C. Produces hormones 1. hCG (syncitiotrophoblasts) 2. PLGF 3. local production of *Indoleamine 2,3, deoxygenase (IDO) destroys tryptophans on maternal T cells rendering them inactive as they approach the placenta* 4. *Somatomammotropin* (gives fetus priority of maternal blood glucose. Can cause mother to become temp. diabetic)
Amniotic Banding
Amniotic Banding 1. Results from amniotic membrane tears allowing legs, arms, fingers, head or face to become constricted. May result in amputations or craniofacial deformities.
Maturation of the umbilical cord
Amniotic sac is covering the umbilical cord. GI loop has to come back in or else a diverticulum will form
Tracheal Esophageal Fistulas (TEF)
Anatomy of most common TEF 1. Baby swallows and fluids spill over into trachea and into lungs 2. Fixed with surgery B. TEFs are associated with family of defects called *VACTERL DEFECTS* 1. Vert. Anomalies 2. Anal Atresias 3. Cardiac Defects 4. TEFs 5. Esophageal Atresias 6. Renal Anomalies 7. Limb Defects
Intestinal Formation
Around 7 weeks of development The midgut is forming the dervatives of the Small Intestine The primary intestinal loop then Rotates 90 deg (Purple arrow) in B and C. *It also temporarily Herniates into the umbilicus, leaving the embryos body* D and E) Around 11 weeks the Gut completes its rotations as the Cecum finds its place inferior to the liver. Note by week 12 the Cecum descends pulling down the Proximal hindgut forming the Ascending colon
What does a 6 Week Embryo look like and what is the Jelly of Wharton
Between week 6-8 the entire structure is surrounded by amniotic membrane creating the primitive umbilical chord 1. Excess intestinal endoderm can enter the chord resulting in an umbilical hernia but usually withdrawn back into fetal abdomen by Week 24-26 B. *Arteries and veins are enmeshed in a proteoglycan-based substance called Jelly of Wharton* arteries, veins, and mesoderm are surrounded by this gelatinous material
Formation of the umbilical cord blood vessels
Blood vessels undergoing angiogenesis enter the connecting stalk around week 3
Early lung Development 6-12 Weeks
Buds are proliferating into mesenchyme (happens to be mesoderm here) growing caudily and laterally in Pericardioperitoneal Canals The Mesoderm covering the buds and bronchioles become Visceral Pleura These secondary buds represent the future lobes of the lung a. Three on right b. Two on left
Laryngeal Development
C. Internal Side of Dev. Larynx from Arches 1-6 1. Entire lining is comprised of endoderm 2. Underlying Cartilage and muscle is derived from Mesoderm and Neural Crest 3. Arytenoid Swellings come from mesoderm proliferation between arches 4-6 around Laryngotracheal orifice i. By week 6 into 7 the L.O. is transformed into a T-shaped opening bordered by the Primordial epiglottis D. Underlying Mesoderm and Neural Crest 1. Signals the overlying endoderm of larynx to proliferate 2. Endoderm proliferation of Primordial Epiglottis closes the L.O. at week 7.5. AT week 10 the L.O. is recanalized and is now the Primordial Glottus.
By what day has the primitive streak formed?
Day 15
Formation of the umbilical cord
Derived from extraembryonic mesoderm at posterior end of disc
Laryngeal Developmente 6-12 Weeks
E. Innervation of Future Musculature of Larynx 1. Tenth Cranial Nerve innervates the derivatives of 4th Arch i. Superior Laryngeal Branch of 10th Cranial Nerve ii. Recurrent Laryngeal Branch of 10th Cranial Nerve innervates derivatives of 6th Arch.
Most important Slide of Placenta Primer
End of Month 2 (10-12 Weeks) End of Month 3 (15-17 Weeks) In first picture take note where each of the decidua tissues are. *chorionic cavity is being filled up by the amniotic cavity* *At the end of Month three the decidua parietalis, chorion laeve, and amnion have all FUSED* *uterine cavity is tiny at this point, (little white triangle below baby's head)*
What is the allantois?
Filters wastes, but is only around for a few days
Dizygotic Twins
Formed as ovary releases two eggs. Each are fertilized by a single sperm Usually develop separate placentas (A) Chorions can fuse as in (B) *a. Can lead to erythrocyte mocaicism Mom is type A Dad is type O Fetuses can be A and O*
What do syncytiotrophoblasts secrete?
HCG into the Mother's blood vessels.
Implantation Embryonic Day >21(Uteroplacental Circulation-Hemochorial type)
Hemochorial - mother's blood is now in direct contact with the *chorion* but not the embryo
How is the liver formed?
Hepatic diverticulum (liver bud) will grow from the *Lesser mesentary AKA ventral mesentary* and grows into the *septum Transversum *- a mesoderm structure that separates the pericardial cavity from the peritoneal cavity The portion of the ventral mestentary that holds the liver is the *lesser omentum*. The *Falciform Ligament* attaches the liver to the body wall. A&B = 4-5 weeks C&D = 5-6 weeks
Formation of lung buds and Larangeal development
I. Respiratory diverticulum (endoderm) protrudes from foregut A. Sets up the proximal-distal axis 1. Consists of two distinct epithelial cell subpopulations: Proximal Bronchiolar Epithelium and Distal Respiratory Epithelium 2. P-D axis is very important in signaling (signals for lung growth) II. In a Few days the tip of Respiratory diverticulum. has enlarged, followed by division into right and left lung buds III. Concomitantly with R.D. development, the *Primordial Pharynx is developing* (D). A. Esophagotracheal Ridges grow B. Esophagotracheal Ridges fuse resulting in 2 structures a. Esophagotracheal septum b. Laryngotracheal Orifice (laryngeal Inlet) pharyngeal arches are shown as roman numerals in picture (5 fuses with 6)
Monozygotic Twins
Identical, formed from one egg and sperm Can result in three different arrangement of fetal and placental membranes -Embryo possible splits prior to blast formation-Results in separate compartments -ICM splits-Results in shared placenta` and chorionic sac *most common* -Gastrula splits-Results in Shared placenta, chorionic sac, and amniotic sac
Susan Torres Case
In the news-Susan Torres had melanoma that spread to her brain. She was ~17 weeks pregnant when she collapsed and was pronounced brain dead. She was kept alive to allow her baby to grow. The baby was born at 27 weeks. Can Cancer cells penetrate the placenta? Yes, but it is not common Melanomas, leukemias, and lymphomas have been shown to cross the placenta resulting in the fetus developing cancer. < 25% of melanomas in the mother have resulted in melanomas in the baby. Sarcomas have been shown to metastasize to the placenta, but not cross to the fetus
Does the mother's blood touch the embryo directly?
No, it fills in the lacunae created by syncytiotrophoblasts.
Are membranes broken during embryo invasion into the decidua?
No. See day 16 picture
What do the ventral and dorsal mesenteries hold in place?
Note the placement of the developing organs within the gut tube The dorsal mesentary holds many (not all) organs in place (endoderm organs) The ventral mesentary (more about this soon) also holds some organs in place. (endoderm organs) *It is ALSO a source of the tissue that holds the liver, but liver does not come from mesenteries though (endoderm)*
Implantation Embryonic Day >21 (Uteroplacental Circulation-Hemochorial type)
Notice the umbilical artery (blue) and vein (red) Chorion = fetal portion of placenta past the cytrophoblast shell = mom's portion of the placenta (decidual cells)
decidua casularis
Portion of the decidua that is closest to the uterine os
respiratory distress syndrome
Respiratory Distress Syndrome (RDS; or hyaline membrane disease) 1. A common cause of death in premature infants (20%) 2. Results from insufficient surfactant production. Alveoli collapse upon exhalation. a. Treatment includes surfactant replacement therapy b. Glucocorticoid treatment during pregnancy accelerates lung development and production of surfactants.
hydramnios or polyhydramnios
Results from excess amniotic fluid. i. Can result in maternal diabetes ii. Anencephaly iii. G.I. Defects
Rh incompatibility
Rh Incompatibility 1. Proteins on the surface of RBCs 2. If mother is Rh (-) and fetus is Rh (+) and fetal RBCs leak into Mom's Circulation, the mother's immune system will mount a response. Usually affects second baby not the first a. The response can be minimal or significant where maternal antibodies are translocated across the placenta destroying fetal RBCs causing severe anemia called erythroblastosis fetalis b. Alternatively, hydrops can form. This is the accumulation of water in the fetus. Excess water and a buildup of bilirubin, a breakdown product of hemoglobin, in the fetal circulation can lead to cerebral damage and sometimes fetal mortality B. Diagnosed by spectrophotometric analysis of amniotic fluid Although about 30 years ago fetal mortality was high, now it is rare due to Rh immunoglobulin injections.
What does omentum mean?
Sac
High Magnification of Tertiary Villi
See picture. Mom's blood is bathing all of this.
Take Home Message for Intestinal Development
Summarizing the final positioning Of the gastrointestinal organs With respect to the body wall TAKE HOME MESSSAGE The small intestine undergoes Rotations, elongates, herniates, retractions, and displacements to form the final GI tract within the fetus. The GI Tract is formed by week 14 of development. After which the organs Mature and grow. *if small intestine does not un-herniate, you will get a henia right above the belly button*
How does the placenta mature and what prevents the mother's blood from mixing with the fetus' blood
Tertiary Villi keep branching (A and B) and form terminal villi. Maternal blood does not mix with fetal blood 1. *Blood separate by Cytotrophoblasts, Syncytiotrophoblast cells, Extraembryonic mesoderm, and endothelial cells lining each capillary*
What do cytotrophoblast cells do?
The continue differentiating into syncytiotrophoblast cells.
Cotyledons
The cotyledons are formed by the septa. Some are deep, some are tiny. *Malformations of these can indicate a defect. Example - the heart of the baby would have to work much harder if the septa did not allow for the Mother's blood to properly circulate*
Summary Card of Gut Primer
The definitive endoderm arises from ectoderm that has engressed through the primitive streak Embryonic folding 3 dimensionally gives rise to the tube-in-tube body plan. The inner tube becomes the gut endoderm The gut endoderm gives rise to not only the GI tract but also the lungs, liver, pancreas, gall bladder, and parts of the pharyngeal arches The Mesentaries (mesoderm tissue) initially hold the gut tube in place. Later they give rise to organs such as the liver (endoderm) and tissues such as the greater and lesser omentum The GI tract undergoes numerous rotations beginning with the stomach, proceding with the Small intestine, and ending with the large intestine. (e.g., cecum). Each of the three regions of the gut tube is vascularized by different branches of arteries that descend from the aorta. Celiac artery-Foregut Superior mesenteric artery-midgut Inferior mesenteric artey-hindgut NOTE: These arteries are used to identify the boundaries of the three gut regions
Summary of Lungs Primer
The definitive endoderm arises from primitive ectoderm that has ingressed through the primitive streak Embryonic folding 3 dimensionally gives rise to the tube-in-tube body plan. The inner tube becomes the gut endoderm The gut endoderm gives rise to not only the lungs but also the GI tract, tongue, liver, pancreas, gall bladder, and parts of the pharyngeal arches The lungs develop from a specified region of the foregut as a diverticulum that becomes bilobed and quickly develops a proximal-distal axis. This axis is important for developing the initial Proximal Bronchiolar Epithelium and Distal Respiratory Epithelium. The larynx forms concomitantly with the initial and later development of the lung buds. The Tenth Cranial Nerve innervates the derivatives of the larynx Maturation of the lungs occurs beginning as early as week 5 of development and proceeds through early adolescence. Congenital lung pathologies are not uncommon. The balance of amniotic fluid within the lungs is important. Too much or too little fluid can cause major lung defects. VACTERL Defects can cause atresias. Note: This primer is only a summary of Lung Development from endoderm. Emphasis is placed on organs and Fetal anatomy that a medical student will see again in gross anatomy.
Where does the extraembronic mesoderm come from?
The epiblast cells that encircled the embryo.
