RDA

describe the process of gastrulation

- during first two weeks of development there are 2 layers of trophoblast (C & S) and 2 layers of embryoblast (bilaminar disc - epiblast and hypoblast) - the cavity surrounded by epiblast = amniotic cavity which is the fluid-filled sac in which the embryo grows - the cavity surrounded by hypoblast = yolk sac which contains primordial germ cells - in the third week following fertilization, a primitive streak forms on the dorsal surface of epiblast and cells of the epiblast start to migrate towards and into the primitive streak - these cells push out the existing hypoblast establishing a new layer of cells between the epiblast and hypoblast - existing epiblast is the ectoderm, new middle layer is mesoderm and existing hypoblast is endoderm - the formation of these three embryonic germ layers completes the process of gastrulation

describe organogenesis of the GI tract & what each part will form

- during the 4th week of development the endoderm folds together forming a primitive gut tube - lateral folding occurs where a portion of the yolk sac becomes incorporated into the primitive gut, with the actual yolk sac pinching off. a small duct remains (vitelline duct) - gut tube divided into foregut, midgut and hindgut and organs begin to form by branching off - foregut forms: proximal duodenum, gallbladder, pancreas, liver, stomach, respiratory tract and esophagus - midgut forms: ascending colon, first 2/4 of transverse colon and the small intestine from the proximal duodenum - hindgut forms: distal 1/3 of transverse colon, descending colon, sigmoid colon, rectum and the upper part of the anal canal - the cloaca is the very end of the gut tube which is separated into the anal and urogenital membrane which will become the rectum and bladder through a process called cloacal sepatation - at the end of week 7 the anal membrane ruptures forming the anal canal

emergency contraceptive pill

- high dose of 1.5mg levonorgestrel (progesterone) - delays ovulation (as inhibits LH) until sperm gone from uterus; thickens cervical mucus; thins endometrial lining

kidney defects

- horseshoe kidneys (kidneys fuse as they ascend from pelvis) - pelvic kidney (failure of kidneys to ascend)

describe the decidual reaction

- implantation triggers decidual reaction around day 12 which is the set of endometrial changes that facilitate embryo implantation - epithelial cells of uterus become enlarged polygonalstromal cells in response to invading syncytiotrophoblast - these form the decidua capsularis preventing trophoblast from invading any further into myometrium - vascularization of the endometrium occurs facilitating blood flow to the developing embryo - decidua basalis grows providing an interface with the trophoblast cell layer (part of the endometrial wall where trophoblast makes contact with) - glycogen and fat droplets accumulate in decidual tissue of uterus providing nutrients to early embryo - decidual tissue also provides an area of immunological inactivity so the embryo is protected from t-cell mediated attack

organogenesis of gonads

- primordial germ cells are created in the yolk sac, which migrate into developing gonads in week 3 while the mesoderm which will form gonads is still indifferent - mesonephric/Wolffian ducts and paramesonephric/Mullerian ducts develop from mesoderm - if Y chromosome is present, SRY protein is produced which causes developing gonads to become testes, producing testosterone. Testosterone stimulates development of the Wolffian ducts. Sertoli cells produce MIS which causes Mullerian ducts to regress. - in the absence of Y chromosome/SRY protein/testosterone, the Wolffian ducts passively regress and the lack of MIS allows for passive development of Mullerian ducts - Week 12: Wolffian/mesonephric ducts differentiate into efferent tubules/epididymis/vas deferens/seminal vesicles and structures descend into the inguinal canal. In females, the Pramesonephric ducts/Mullerian ducts differentiate into the fallopian tubes/uterus/cervix and upper 2/3 of the vagina. Ovaries begin to descend

what are the functions of the placenta

- provide nutrients and remove wastes - produces hCG (maintains corpus luteum and progesterone production preventing more follicle development), estriol (stimulates uterus growth) and placental lactogen (gives fetus priority on glucose from maternal blood) - barrier and transmission of maternal antibodies: downregulation of HLA/antigen presentation, release of maternal immunosuppressive factors, maternal IgG crosses through to placenta providing passive immunity

progesterone only pill - how is it taken - who should it be given to - side effects - mechanism of action

- same time each day or within 3 hours; taken continuously without breaks between packets - indicated for those with a history of migraines with aura or blood clots - side effects include amenorrhoea/menstrual irregularities, acne, low mood, headache, breast tenderness and decreased libido - mechanism depends on the dosage (as high progesterone inhibits ovulation but lower doses allow for some follicular development). main MOA is by thickening cervical mucus, thinning endometrial lining and inhibiting fallopian tube motility

physiological changes during labour

- softening and effacement of the cervix mediated by prostaglandin production - myometrial gap junctions - oxytocin levels increase during second stage of labour promoting uterus contraction - increase in oestrogen: progesterone ratio during labour and the reduced progesterone level allows for contractions (as high progesterone prevents contractions during pregnancy)

physiological adaptation to pregnancy: uterus

- the myometrium and nerves hypertrophy - there is an increase in vascularity of the uterus. - increase in size from 50g to 1.1kg at term - the overall shape changes from pear to ovoid as the size increases. - elastic and fibrous tissues increase and gap junctions appear, which aid uterine contraction during labour. - increase in sensitivity to prostaglandins and oxytocin

describe sperm movement from the vagina and the physiological changes they undergo in order to reach the ovum in the ampulla

1. Capacitation: the glycoprotein coat around the sperm is removed and this signals the start of sperm hyperactivity, which can last for several hours. 2. Acrosome reaction: release of hydrolytic enzymes that breakdown in the zona pellucida and allows sperm to penetrate the zona pellucida. 3. Entry of the sperm nucleus into the oocyte and fusion of the gametes resulting in a diploid zygote (and mitotic division begin) 4. Cortical reaction: cortical granules release enzymes which cause a reaction forming a gel-like barrier and blocks any subsequent sperm entry to prevent polyspermy.

stages of labour

1. Stage 1 ○ Part 1: latent early phase where there are irregular contractions every 5-30min, lasting ~30s, for around 20 hours. The cervix dilates up to around 3cm. Then, regular contractions occur. every 3-5 minutes lasting around 1 minute each. The cervix dilates to up to 6cm. ○ Part 2: active phase with intense contractions every 30s-2min which last 60-90seconds. Cervix dilates to around 10cm 2. Stage 2 - the pushing stage ○ Power (of uterine contractions) ○ Passenger (lie and presentation of fetus) ○ Passage (female pelvis) ○ Prostaglandins (cervical effacement and uterine contractions) 3. Stage 3 - delivery of placenta

taking a history before prescribing hormonal contraception

Along with the usual past medical and family history, should definitely ask re: • CVD • Cancer • Liver/gallbladder disease • Menstrual history • Weight • Medication history

changes in the cervix and uterus before and during parturition

Cervix 1. Softening: occurs throughout pregnancy. Collagen changes as well as fibroblast and epithelial cell proliferation. 2. Ripening: in the last 1-2 weeks of before birth, tissue viscoelasticity increases to a maximum. 3. Dilation: during labour, the cervix shortens, effacement occurs and cervical dilation to 10cm. 4. Repair: following delivery, remodelling occurs to prepare the cervix for future pregnancies and to protect the woman from environmental insults. Uterus In the non-pregnant state the uterus receives just 2% of the total body blood flow. During pregnancy this increases to around 17% of the total body blood flow at term. ↑ vascularization facilitates this increase. Between 80-90% of the uterine blood flow is directed to the placenta.

best time to take folate

Inadequate levels of folate (vitamin B9) may increase the risk of NTDs. Folate is required for the production and maintenance of new cells because it is involved in DNA and RNA synthesis. The most important time to take folate is for ~2 months before getting pregnant and until you are 12 weeks along. This is because this is the time where gastrulation occurs and the formation and closure of the neural tube. NTDs (neural tube defects) are birth defects that occur very early in pregnancy. The defects develop between the 17th and 30th day after conception (four to six weeks after the first day of a woman's last menstrual period), usually before a woman knows she is pregnant. During this critical time of pregnancy, the proper formation and closure of the neural tube, which later becomes the spinal cord, brain, and bone surrounding the spinal cord and brain, normally takes place. An NTD occurs when the neural tube fails to close properly

effects of epidural on haemodynamic changes during labour

Epidural may cause loss of SNS input to the heart causing a significant decrease in HR and BP which may require emergency intervention

define infertility

Infertility is defines as the inability to conceive despite 1 year of trying for a pregnancy. In women over 35 this time frame is lowered to 6 months.

describe the process of fertilization up until formation of embryoblast and trophoblast

Sperm enters cytoplasm of oocyte and the oocyte undergoes meiosis 2 forming an activated oocyte and polar body (which undergoes apoptosis) the male and female pronuclei fuse to become a single nucleus = diploid zygote w/ 46Cr the fertilized ovum will start to move from the fallopian tubes down into the uterus at around 30hrs, zygote will undergo first mitotic division forming 2-cell blastomere. this marks the beginning of cleavage by day 3, the blastomere becomes a ball of 16 cells called a morula after 4-5 days of mitotic divisions the morula forms 2 distinct cell layers: inner cell mass or embryoblast (which forms embryo) and outer trophoblast (which forms embryonic placenta) a fluid filled cavity emerges between these two cell layers and the morula becomes a blastocyst, marking the end of cleavage

organogenesis of liver

Originates from the foregut. When the septum transversum (separates developing heart from midgut) and cardiac mesoderm come into close proximity, livergenesis is induced. Hepatoblasts go on to form the liver bud which will become the liver, gallbladder and biliary duct system This forms inside the ventral mesogastrium, extending into the septum transversum

histological structure & function of epididymis

accumulation, storage and maturation of sperm head/body: water reabsorbed to concentrate the sperm tail: SNS innervation causes contraction during ejaculation. Lots of smooth muscle here. histology - pseudostratified columnar epithelium containing principal cells (for fluid absorption) and basal cells (e.g. stem cells, lymphocytes)

lung organogenesis

week 4: lung bud appears as ventral growth from foregut and develops into a tube. trachea is separated from oesophagus as trachoesophageal ridges close forming the tracheosophageal septum week 5-16: pseudoglandular phase - branching occurs of main bronchi, secondary bronchi and tertiary bronchi - division occurs until terminal bronchioles formed week 16-26: canalicular phase - respiratory bronchioles form - alveoli form - vascularisation of lungs occur where capillaries grow around alveoli epithelia week 26-birth: terminal sac - growth and expansion of terminal alveolar sacs - type 1 pneumocytes and type 2 pneumocytes develop - type 1 form direct contact with capillary forming blood air barrier - surfactant produced (by type 2 cuboidal)

when does embryogenesis occur

weeks 3-8 which is where the fetus is most sensitive to teratogens

irreversible contraceptives

women: - tubal microinsert (insert thing that blocks tubes) - tubal ligation (reversible) - hysterectomy males: - vasectomy where vas deferens tied (reversible if under 10y). Need at least 2 negative sperm counts before it can be relied on as the only method of contraception. Risk is that antisperm antibodies may form if sperm escapes into the blood, and sperm granulomas may form

Briefly discuss how an infant with transposition of the great vessels would be affected by the changes of post-birth circulation

· Transposition of great vessels - aorticopulmonary septum grows straight down rather than spiralling down. This causes the vessels to enter the wrong ventricles e.g. aorta from RV and pulmonary trunk from LV Ø Cycling of blood between the ventricles - no oxygenated blood reaches the body / deoxygenated blood does not reach the lungs for reoxygenation! Ø Before birth - blood can cross between the left and right sides through foramen ovale, ductus arteriosus and VSD Ø After birth, the shunts close which can cause death. Given IV prostaglandin E to keep the foramen ovale open OR rip open the interatrial septum using a balloon at the end of the catheter. Diagnosis is usually made antenatally

what to do with embyros after IVF

• Freeze for your own future use • Destroy • Donate to others • Donate to science • Compassionate transfer

information to get from a couple experiencing infertility

• Frequency and timing of intercourse (best days are days 12, 13 and 14) • Lifestyle factors e.g. smoking, BMI, alcohol, coffee, recreational drugs, environmental toxins and pollutants (ask what occupation they are) • Medical conditions e.g. woman: PCOS, adhesions, tubal blockages, PID, endometriosis; man: testicular defects, impotence, difficulty with erection have they had semen analysis, previous undescended testicle; both: cardiovascular disease, endocrine disorders • Previous surgeries e.g. vasectomy, sterilization • Pregnancy history - Total number of all pregnancies, full term deliveries, live vs stillborn, miscarriages less than 20 weeks, ectopic/tubal, terminations, any with birth defects, were other pregnancies with previous partners • Length and regularity of menstrual cycle, how much bleeding, pain with periods • Prior use with ARTs/IVF • Previous exposure to chemotherapy or radiation • Previous STDs • Current medications • Sexual dysfunction • Diet/exercise • Age • Family history

physiological adaptation to pregnancy: respiratory system

• High progesterone → ↑ total body consumption of oxygen • Diaphragm is elevated by uterus pushing against it which makes it more difficult to breathe comfortably (decreasing ERV & FRC), but this is compensated as progesterone relaxes the sternal ligaments of the ribcage allowing an ↑ inspiratory capacity in compensation and preservation of vital capacity • The relative hyperventilation that occurs (shallower breathing) decreases arterial CO2 (as blowing it off lots) leading to a mild respiratory alkalosis, but this actually enhances placental transfer of CO2 from the fetus back into mums blood • ↑ progesterone levels decrease CO2 threshold to compensate and respiratory centre becomes more sensitive to CO2 levels → causes hyperventilation and dyspnoea in 65% of women

defects in respiratory organogenesis

• Lack of surfactant: Babies born before 28 weeks gestation have not undergone cell differentiation and thus will not be able to make surfactant. Usually this will be given exogenously e.g. curoform until the cells have developed • Tracheoesophageal fistula: in week 4 (day 28), respiratory diverticulum (primitive respiratory tract) starts to grow from ventral foregut into surrounding mesoderm, forming the lung buds and laryngotracheal tube. Posterior part of trachea at first open to esophagus but eventually a septum will form, separating the the laryngeotracheal tube form the oesophagus. If the septum does not develop properly the baby will vomit it's first feed and the vomit will be very frothy due to high O2 content. • Congenital diaphragmatic herniation: dorsal/posterior portion of diaphragm fail to join with pleuro/peritoneal membrane meaning abdominal organs like intestines are able to enter into pleural cavity. Crush lungs preventing them from developing normally.

physiological adaptation to pregnancy: renal

• ↑ cardiac output = ↑ renal blood flow = ↑ GFR = ↑ urinary output • ↑ urinary frequency results, and also from uterus pressing on bladder • Kidneys increase in size to accommodate extra blood flow resulting in dilation in the ureters and calyces • Progesterone is smooth muscle relaxant causing hypomotility of the ureters which can cause urinary stasis within the kidneys, which combined with the ↑ capacity of kidneys/ureters to store urine increases risk for upper UTI

physiological adaptation to pregnancy: gastrointestinal

• ↑ hCG levels cause nausea, vomiting and heartburn • Progesterone increase can cause cravings • Progesterone lowers tone of oesophageal sphincter resulting in heartburn/reflux • Lower pH levels increases risk of dental caries and can cause soft, swollen gums • ↑ abdominal pressure can result in haemorrhoids • ↓ gut motility due to progesterone which increases absorption but also causes constipation and bloating just think: most of the effects caused by placental hormones: HCG = heartburn; Progesterone = PICA & peristalsis

what two muscles surround the vagina

ischiocavernosus and bulbospongiosus

bulbourethral fluid

Bulbourethral fluid is picked up making up around 5% of the semen volume. It contains mucoproteins which are important in lubrication of the distal urethra.

describe the normal fetal presentation

longitudinal lie w/ head flexed, cephalic occipitoanterior presentation

In order to identify whether Sue is ovulating which hormone would you measure and when in the menstrual cycle would you measure it?

midluteal progesterone test on day 21 too difficult to measure LH!!

ovary blood supply

ovarian artery from abdominal aorta which travels in suspensory ligament

immunoregulation in pregnancy

some of the physiological changes necessary for fetus survival also affect the maternal immune system an immune response may develop to GnRH, hCG, ovum, zona pellucida, and proteins produced by the placenta - TGF-beta cytokine produced stimulating switch to TH2 mediated immunity (antibodies), instead of TH1 immunity (cytotoxic T cells) which is much more aggressive. This helps with maternal/foetal tolerance but increases the susceptibility of the fetus to infections requiring TH1 responses - limited expression of HLA by the placenta meaning MHCI and II antigen levels are low and it isn't seen as a threat by the maternal immune system - placenta produces CD59 which inhibits complement activation - placenta produces IL10 cytokine which dampens down other immune responses C = CD59 decreases complement H = HLA expressed less, MHC/MHC2 I = IL10 - other immune responses T = TGFB - TH2 immunity

blood supply to testes

testicular artery from abdominal aorta

hormone produced by Leydig cells

testosterone

uterus blood supply

uterine artery from internal iliac which branches into straight and spiral arteries uterine artery travels in cardinal ligament

vaginal blood supply

vaginal artery from internal iliac

combined oral contraceptive pill - effectiveness - indications - contraindications - mechanism of action - risks - benefits - interactions

- 99% if taken perfectly and 92% typical use (highest risk of pregnancy is after placebo pills have been taken - thus shouldn't take them!) - prescribed for contraception, heavy bleeding, primary hypogonadism, pelvic pain, ovarian cysts and PCOS - oestrogen in the pill suppresses GnRH/LH/FSH so that follicular development doesn't occur. Follicle doesn't develop = oestrogen not produced by follicle either = LH surge doesn't occur = ovulation doesn't occur - progesterone in the pill thickens cervical mucus inhibiting sperm entry into the uterus - side effects include irregular bleeding, nausea, headaches and breast tenderness - contraindications include prolonged immobilisation, AF, migraine with aura, breast cancer, impaired lipid metabolism and diabetes with vascular impairment I AM BLD (i am bleeding) (immobilisation, AF, migraine, breast cancer, lipids, diabetes) - risks include: liver, cervical and breast cancers; DVT & PE; MI; HTN; stroke - while taking medications such as anticonvulsants (carbamazepine and phenytoin), St Johns Wort, and antibiotics (rifampicin) that induce CYP3A4 (which metabolises COC), the COC will be metabolised more rapidly thus reducing its contraceptive effect. thus, during this time the medication is taken another form of contraception should be used and used for 4 weeks afterward as well - benefits of taking the pill include prevention of acne, bone thinning, ovarian cysts, endometrial and ovarian cancers, iron deficiency anaemia, PMS symptoms and lower risk of ectopic pregnancy. Other benefits include that periods will be regular and easier to predict, it is easy to use, doesn't get in the way of sex and fertility returns as soon as you stop taking it

depo provera

- LARC - IM injection of progesterone given at 90 day intervals - thickens cervical mucus, thins endometrial lining and inhibits fallopian tube motility - over 99% effective - increases risk of breast cancer and bone problems - may contribute to IGT - side effects include amenorrhoea/menstrual irregularities, acne, low mood, weight gain, headache, breast tenderness and decreased libido

intrauterine devices

- LARCs - 5 years - 99% effective - copper: releases copper ions which are toxic to sperm; can be used as an emergency contraceptive up to 5 days - mirena: produces progesterone (levonorgestrel) which reduces LH secretion enough to prevent ovulation, thickens cervical mucus, inhibits falloptian tube motility and thins endometrial lining. it is the most effective form of contraception - contraindicated in PID, STIs, pregnancy, uterine bleeding, vaginal abnormalities or any other gynaecological infections

contraceptive arm implants

- LARCs - jadelle inserted into skin providing slow-release of progesterone - provides 5 years contraception - over 99% effective - contraindications include pregnancy, liver disease or a history of breast cancer - side effects include amenorrhoea/menstrual irregularities, acne, low mood, weight gain, headache, breast tenderness and decreased libido - small risk for infection after insertion

functions of amniotic fluid

- absorbs jolting which protects fetus - prevents adherence to surrounding tissues - allows for movement - prevents drying out

describe the process of implantation

- by day 7-9 post-fertilization, blastocyst hatches out of the zona pellucida and implantation begins - initial adhesion of blastocyst to endometrium occurs, activating trophoblasts - blastocyst migrates into endometrium and leaves a coagulation plug where it enters the uterine wall - after initial adhesion, trophoblast differentiates into inner cytotrophoblast and outer syncytiotrophoblast - syncytiotrophoblast burrows further into the endometrium which then envelops the blastocyst - as syncytiotrophoblast burrows, lacunae form within the endometrium and fill with maternal blood - after implantation, trophoblast cells secrete HcG which prevents degeneration of the corpus luteum, sustaining oestrogen and progesterone levels and prevents shedding of endometrium - the process of implantation is completed by day 10

amniocentesis

- can be done after 14w gestation - 20ml amniotic fluid removed transabdominally - this fluid contains fetal cells that have been shed - culture isolated for analysis but can take up to 2 weeks - safer than chorionic villus sampling with a miscarriage risk of 0.2% or 2 in 1000 remember - A A 4 4 (amniocentesis is abdominal, 14 weeks, NOT 48hrs)

chorionic villus sampling

- can be done from 10-12 wees gestation - sample of villus tissue from the trophoblast/chorion taken transabdominally or transvaginally - this tissue is derived from same precursor cells that form fetus thus have same chromosomal makeup - culture results available within 48hrs - more risky than amniocentesis with a miscarriage risk of 2% or 2 in 100

3 examples of long acting reversible contraceptives

- depo provera - jadelle - IUDs (copper and mirena)

organogenesis of the heart

- development begins week 3 where progenitor cells migrate from mesoderm to primary heart field at cranial end of embryo, forming myoblasts and blood islands - the endoderm secretes VEGF signalling cells to organise into 2 endothelium lined heart tubes - each receives blood from a vitelline vein from the yolk sac and the blood exits each tube via the dorsal aorta - the heart tubes then fuse to become one tube - the vitelline veins fuse to form the sinus venosus - the dorsal aortae fuse to become a single aortic outflow - at this point have atrioventricular canal/primitive atrium and primitive ventricles - atrioventricular canal starts to divide as endocardial cushions begin to form from dorsal and ventral walls of canal, growing inwards and dividing the atria into two channels - in the roof of the cushions there is a downward growth of the septum primum which grows downwards between the atria - a hole in the septum forms by apoptosis called the ostium secundum - to the right of the septum primum a second septum called the septum secundum grows downwards towards the cushions and stops before reaching the end. As a result, an opening is left and forms the foramen ovale. This allows shunting of blood from the right side of the heart to the left (closes at birth) - an interventricular ridge forms at the bottom of the heart and a muscular septum grows from this upwards towards the cushions, at the same time as a membranous septum grows top down from the cushions - these septae fuse separating the ventricle into 2 compartments - the common outflow tract which is referred to as the truncus arteriosus twists to form the aorta and pulmonary trunk

describe the formation of the placenta

1. The placenta is the maternal layer closest to the developing fetus. By day 7 or 8, the fetus implants on the surface of the endometrial wall and the point of contact is called the decidua basalis 2. Formation of the placenta begins when blastocyst adhesion occurs and the trophoblast divides into 2 layers, the cytotrophoblast and the syncytiotrophoblast. The cytotrophoblast is an inner layer of mononucleated cells, and the syncytiotrophoblast is an outer layer of multinucleated cells with no distinct cell boundaries. 3. To replenish the number of syncytiotrophoblast cells, cytotrophoblast continuously sends out cells into the syncytiotrophoblast, which lose their cell membranes to form a large multinucleated mass 4. Around day 14, primary villi are formed all the way around the fetus, and cells start to clear out from between the primary villi leading behind empty spaces in the syncytiotrophoblast called lacunae. During this time the bilaminar disc is formed. 5. Spiral arteries and veins from the mother start to grow into the decidua basalis and merge with the lacunae so they become filled with maternal blood. 6. Villi in the junctional zone (where maternal and fetal circulation is in close contact) continue to grow whereas villi outside of it regress. 7. Extraembryonic mesoderm forms between the bilaminar disc of the embryo and trophoblast. A core of this grows into villi (secondary chorionic villi). Around day 17, fetal vessels (arteries, capillaries and veins) begin to form within these villi (tertiary chorionic villi) helping to increase the surface area of the maternal-fetal barrier. The tertiary villi are bathed in maternal blood but there is no direct contact between the two 8. Another cavity forms within the extraembryonic mesoderm known as the chorion. This is an intermediate layer between the amnion and the placenta. A small part remains - the vitelline stalk - which connects the embryo to the placenta. The body stalk later forms the umbilical cord which consists of 2 umbilical arteries and veins. 9. The tertiary villi undergo regression to form the smooth, outer chorion laevae. Some of the trophoblastic villi remain in contact with the uterine wall, forming the functional part of the placenta - the chorion frondosum. This is highly vascularised and thus if near the cervix can cause a massive haemorrhage during delivery 10. The maternal contribution to the placenta is known as the decidua and lines the uterus wall. Its parts include the decidua parietalis (covering the uterine wall), the capsularis (covering the chorion laevae) and the basalis (covering the chorion frondosum) 11. The chorion is well defined at 8-12 weeks gestation. Over time, the amniotic cavity and embryo grow, obliterating the chorionic space. Eventually by 3-4 months the amnion fuses with the chorion. After this time, growth of the fetus causes growth of the uterus as well

transport of sperm from seminiferous tubules

1. develop in seminiferous tubules forming a head/acrosome containing enzymes (for penetration of oocyte) and neck containing mitochondria 2. move into epididymis where they mature more, they are here for around 2 months 3. travel through the vas deferens to the ampulla where they are joined by seminal fluid from the seminal vesicles 4. travels from the ampulla to ejaculatory ducts where they are joined by prostatic fluid 5. travels into urethra and joined by bulbourethral fluid

describe the process of spermatogenesis

1. during develop in utero, spermatogonia (46/diploid/2n) migrate from yolk sac to testes; remain dormant til puberty 2. at puberty, spermatogonia undergo mitosis to produce type A and B spermatogonia 3. type A undergo mitosis only serving as stem cells whereas type B differentiate into primary spermatocytes (2n) 4. primary spermatocytes will undergo meiosis 1 forming 2 haploid secondary spermatocytes (n) 5. secondary spermatocytes undergo meisosis 2 forming 2 spermatids each with 1 chromatid from each of the 23 chromosomes 6. spermatids develop accessory structures becoming mature spermatozoa

describe the process of oogenesis

1. primordial germ cells form around 5-6w gestation and migrate to ovaries where they differentiate to oogonia 2. oogonia undergo mitosis producing 2n primary oocytes, but halting at prophase I of meiosis I 3. primary oocytes are surrounded by granulosa cells forming primordial follicles from infancy to puberty 4. at puberty, a few of the primary follicles develop into secondary follicles each menstrual cycle 5. each month, the first follicle who's granulosa cells (which have had FSH receptors so far) develop LH receptors will mature to become a graafian follicle while the other secondary follicles will die through atresia. Meiosis I is completed by the oocyte to form a secondary oocyte (and first polar body), which continues into meiosis II but is halted at metaphase 2 6. The graafian follicle bursts during the LH surge, expelling the oocyte out of the ovary. Meiosis II is completed if the secondary oocyte is fertilised, briefly forming an ovum and second polar body.

when is the most common time for parturition

37-42 weeks

diaphragm as a contraceptive

A reusable synthetic disc which is inserted into the vagina to cover the cervix and prevent sperm from entering. It should be used with spermicide and needs to be left in place for 6 hours following intercourse. The choice of diaphragm is dependent on the shape and size of the cervix and a trained person is needed to do the initial fitting. Contraindications include vaginal structural abnormalities and recurrent UTIs.

describe how a ventricular septal defect may result

A ventricular septal defect is a defect/hole in the ventricular septum which is the wall which usually divides the left and right ventricles of the heart. Such defects may be a result of both genetic and environmental factors. The ventricular septum consists of an inferior muscular portion and superior membranous portion. Most commonly, the defect occurs in the membranous part of the septum, where several embryonic tissues converge. Because the pressure of blood in the LV is higher than in the right, this lesion is initially associated with left-to-right shunting of blood. The oxygen-rich blood then gets pumped back to the lungs instead of out to the body, causing the heart to work harder.

organogenesis of pancreas

Around week 4-5 of development, two buds develop from the foregut. These buds are located just below the stomach and are called the ventral bud and dorsal bud. The ventral pancreas rotates towards the dorsal pancreas due to the rotation of the duodenum. These two structures fuse to become the adult pancreas which secretes insulin by week 10

natural contraception

Avoiding or planning pregnancies by trying to identify the fertile period and thus timing sexual intercourse appropriately by assessing: • Temperature changes • Cervical mucus thickening • Uterus position • Length of the cycle • Ovulation Methods include abstinence, prolonged lactation and coitus interruptus

describe primary causes / gonadal causes of infertility in males vs females

Males - mumps - DNA damage to sperm from radiation, smoking or chemotherapy - STIs - Klinefelter's XXY - microdeletion of Y chromosome - cryptorchidism - environmental e.g. alcohol, smoking, obesity, underweight, caffeine, drugs, solvents Females - depleted oocytes to begin with - premature menopause - STIs - genetic translocations - DNA damage to oocytes caused by radiation, smoking or chemotherapy - environmental e.g. alcohol, smoking, obesity, underweight, caffeine, drugs, solvents

maternal changes following parturition

Following parturition, it can take mum up to six months to return to baseline functioning: • Blood volume decreases to baseline over 3 days • Bradycardia improves over the 2-3 weeks following birth • Blood pressure can stay elevated for up to 3 months • Weight changes may take longer to correct; ~6m remember 3 days = blood volume returns 3 weeks = bradycardia improves 3 months = blood pressure 6 months = weight

describe IVF

Funded in NZ for those who meet strict criteria. Process includes: 1. Ovarian hyperstimulation: ○ GnRH agonist suppresses endogenous GnRH, LH and FSH production, stopping spontaneous/natural ovulation. Suppression of ovulation is required because oocyte retrieval of the mature egg from the fallopian tube or uterus is much harder than from the ovary. ○ FSH analogues injected to hyperstimulate ovaries. This causes multiple follicles to develop. 2. Progesterone therapy given to increase success rate of implantation, complementing the function of the corpus luteum 3. hCG (trigger shot) is administered via injection to induce final maturation of oocytes. This acts as an analogue of LH and send the eggs into meiosis so that the number of chromosomes half to 23 prior to egg retrieval 4. Transvaginal oocyte retrieval occurs just prior to when follicles would rupture, usually ~35hrs after hCG injection. A needle pierces the vaginal wall to reach the ovaries, guided by ultrasound imaging. Follicles are aspirated through the needle. 10-30 eggs are retrieved. 5. Oocyte insemination to achieve fertilisation - the sperm and egg are incubated together at 75000:1 6. Embryo development - culture occurs for 4-5 days until cleavage or blastocyst stage with 2-3 embryos usually formed 7. One of the embryos is transferred back to the uterus using a catheter, and the remaining ones are frozen for any subsequent procedures

where are sertoli and leydig cells found, what hormone do they make and what function do they have

Leydig cells - respond to LH - found in interstitium - release testosterone to support stermatogenesis (as bind to sertoli cell receptors) and induce 2ndary sec characteristics (growth, pubic hair etc, libido) Sertoli cells - respond to FSH AND testosterone - found in seminiferous tubules - produce proteins for nurturing sperm and promote spermatogenesis - release inhibin - have both testosterone and FSH receptors

pregonadal/secondary causes of infertility in males vs females

Males - Kallman's syndrome (mutation in Anosmin-1 means GnRH neurons fail to migrate) - Secondary hypogonadism (pituitary failure) Females - Secondary hypogonadism (pituitary failure) - Underweight - Hyperprolactinaemia (supresses ovulation and decreases progesterone release during luteal phase)

describe the nerve control of erection and ejaculation

PNS innervation - pelvic splanchnic nerves (S2-S4) control erection whereby deep arteries of the penis (from internal pudendal) fill the lacunae of the corpora cavernosa with blood SNS innervation - T12-L2 sympathetic chains cause semen to be emitted from the accessory glands into the urethra by strong spasmodic contractions the arteries then constrict and the penis becomes flaccid blood drains out through the superficial and deep dorsal veins of the penis

condoms

PROS - cheap - readily available - STI protection CONS - leaks and breaks - latex allergy - reduced sensation - 98% effective if used perfect but 85% in typical use because sometimes it slips off or breaks, its too large or its not put on before penis touches vagina

Please list the three stages of labour and briefly (in a sentence or two for each) explain what occurs in these three stages

Part 1: contractions occur and cervix dilates up to around 10cm Part 2: uterine contractions cause birth of the foetus Part 3: placenta is delivered

define fecundity and the factors that affect it

Probability of conceiving in 1 menstrual cycle (~20%) • Age (fecundity declines at 30) • Timing of intercourse (maximum fecundity is achieved 1-3 days before ovulation on days 12, 13 and 14) • Frequency of intercourse • Presence of antisperm antibodies • Retrograde ejaculation

organogenesis of kidney

Renal development occurs in stages, starting at around week 4 1. Pronephros reside in the cervical region as non-functioning primitive kidneys (develops at start of week 4 but degenerates by end of week 4) 2. Nephric duct extension occurs and the pronephros extend down caudally 3. Mesonephros. At around week 5, ureteric buds form from the mesonephric duct. The buds interact with the surrounding mesenchyme and begin to form the adult kidney. The mesenchyme forms the cortex and medulla of the kidney and the metanephros will form the minor/major calyces and renal pelvis. Initially these kidneys are in the pelvis but will ascend as the embryo grows. The ureters, collecting ducts and renal pelvis also develop from the uretic bud. The bud grows and dilates to form these structures. 4. By the end of the first trimester the kidney has started functioning.

What public health approaches could be utilised with the aim of reducing the number of pregnancies affected by neural tube defects?

The current New Zealand policy is to recommend that women planning a pregnancy take 800 µg of folic acid daily for four weeks prior to conception and for 12 weeks after conceiving to reduce the risk of NTDs (remember - 800-4012) - Subsidise folic acid - Could mandatorily fortify flour, cereal, pasta, grains etc with folic acid. In NZ it is currently only voluntarily. - Education - Lifestyle changes e.g. reduce obesity, promote healthy lifestyle, reduce substance abuse, reduce T2DM as these are all risk factors

describe the second 14 days of the menstrual cycle

The 14 days post-ovulation is referred to as the luteal phase of the cycle, which corresponds to the secretory phase of the endometrium. The remnant of the ovarian follicle becomes the corpus luteum. Theca cells continue secreting androstenedione, and the granulosa cells keep converting it to 17β-estradiol, as before. However, granulosa cells (which grew LH receptors before) then begin respond to low LH concentrations by secreting progesterone, rather than oestrogen, and so progesterone overtakes oestrogen as the dominant hormone during this time. Progesterone acts as a negative feedback signal decreasing FSH and LH release. At the same time, the granulosa cells also secrete inhibin, which also inhibits FSH release. This is to prevent another follicle from growing as during this time fertilization could be occurring during the uterus. Oestrogen levels decline and combined with rising progesterone levels, signal ovulation has occurred thus help make the endometrium receptive to the implantation of a fertilized gamete. The uterus enters the secretory phase of the endometrial cycle under the influence of high progesterone, where spiral arteries continue to grow and uterine glands begin to secrete more mucus. After day 15, the cervical mucus starts to thicken and the corpus luteum degenerates into the corpus albicans. The corpus albicans doesn't make hormones, so estrogen and progesterone levels slowly decrease. When progesterone reaches its lowest level, the spiral arteries collapse, and the functional layer of the endometrium prepares to shed through menstruation. This shedding marks the beginning of a new menstrual cycle and another opportunity for fertilization.

describe the first 14 days of the menstrual cycle

The first 14 days leading up to ovulation is referred to as the follicular phase of the cycle, where menstrual and then proliferative changes occur in the endometrium. The hypothalamus secretes GnRH during this time causing nearby APG to release FSH, and LH. These hormones control the maturation of ovarian follicles, each of which is initially made up of a primary oocyte, surrounded by layers of theca and granulosa cells. During the first 10 days, theca cells develop receptors which bind LH, and in response secrete androstenedione. Several follicles containing oocytes begin to develop, as the early stages of this development does not require much LH. Granulosa cells develop receptors which bind FSH, and in response secrete the enzyme aromatase. Aromatase converts androstenedione from the theca cells into 17β-estradiol, which is a member of the estrogen family. During days 10-14, granulosa cells also develop LH receptors. As the follicles grow and more estrogen is released into the bloodstream, the oestrogen acts as a negative feedback signal to the APG telling it to release less FSH. As a result of ↓ FSH, some of the developing follicles in the ovary will stop growing, regress and die off via atresia and apoptosis. The follicle that has the most FSH receptors will continue to grow, becoming the dominant follicle that will eventually undergo ovulation. As blood oestrogen levels start to climb higher and higher, it becomes a positive feedback signal to the APG making it secrete a whole lot of LH/FSH. This surge happens a day or two before ovulation and stimulates the rupture of the follicle and expulsion of the oocyte. During this time, the uterus is preparing the endometrium for implantation and maintenance of the pregnancy. Firstly, menstruation occurs where the old endometrial lining is shed through the vagina. This is followed by the proliferative phase where high oestrogen from the follicle stimulates thickening and growth of the endometrium, and emergence of spiral arteries. The cervical mucus also becomes thinner making it more hospitable to incoming sperm.

describe the menstrual cycle i.e. changes to endometrium

The menstrual cycle refers to the progress of changes in the endometrium (lining of the uterus) and occurs at the same time as the ovarian cycle. It is separated into the proliferative and secretory phase. Proliferative phase Days 1-5 where the endometrium is shed. Menstruation is triggered by the low progesterone levels as the corpus luteum involutes after ovulation. It involves contraction of the endometrial arteries and the subsequent sloughing of the endometrium. The post-menstrual/proliferative phase occurs on days 6-14, and is triggered by the rising oestrogen levels that are the result of a new follicle maturing. Oestrogen stimulates thickening of the endometrium as well as development of glands and coiled arteries. Secretory phase Days 15-28 of the cycle. Changes in the endometrium are stimulated by the progesterone secreted by the corpus luteum following ovulation. Progesterone stimulates thickening of the endometrium and endometrial gland growth. The secretory phase is also associated with an increase in core body temperature.

describe the process of neurulation & what brain structure each part of the neural tube will form

The process of the neural tube developing is called neurulation. Following gastrulation, the formation of the trilaminar disc, a portion of the ectoderm called the notochord induces overlying ectoderm to develop into two neural folds on either side of a neural groove. This is the formation of the neural plate. The neural folds bring the edges of the neural plate together and start to fold it to form the neural tube. Once the two folds meet, the cells of the neural fold transition into neural crest cells which disconnect from the ectoderm above (which will become skin) and eventually migrate away to form the peripheral nervous system. The epithelial cells lining the neural tube will form all the neurons of the CNS. The neural tube begins to close from the centre out to rostral and caudal ends. The rostral and caudal neuropores are thus the last to close. The notochord degenerates and only persists as the nucleus pulposus of the intervertebral discs. The forebrain, or prosencephalon, will form the telencephalon (cerebrum) and diencephalon (thalamus, hypothalamus, epithalamus). The mesencephalon will form the midbrain. The rhombencephalon, or hindbrain, will form the metencephalon (pons and cerebellum) and myelencephalon (medulla).

somatic nerve to the penis (carrying touch and temperature)

The somatic nerve of the penis is the dorsal nerve of the penis, which is a branch of the pudendal nerve and carries general sensation such as touch and temperature. The pudendal nerve itself originates from the sacral plexus and carries fibres from the spinal cord levels S2-S4.

describe stomach organogenesis & physiological herniation

The stomach begins as a growth of the foregut tube. As the organ develops, the dorsal side grows faster than the ventral side. This causes the larger dorsal side to rotate left and this becomes the greater curvature, whereas the smaller side on the right becomes the lesser curvature. The mid-gut grows at a faster rate than any other structure in the embryo. Around week 4 the first part of the gut is forced out through the umbilicus into the amnionic space, resulting in a physiological herniation. In week 10 it goes back into the normal abdominal cavity The stomach then rotates 90 degrees clockwise (from above perspective). This moves the greater curvature to the left side of the body and lesser curvature to the right side. Then it rotates another 180 degrees to sit in the formation we see in the fully developed abdomen. An omphalocele results if the midgut does not re-enter the abdominal cavity.

prostate gland fluid

This makes up 20-30% of semen volume. This fluid contains sugars, enzymes, PSA (for breaking down cervical mucus) and is also alkaline.

seminal vesicle fluid

This makes up ~60 of semen volume. The alkaline nature of the fluid assists in neutralizing the vaginal acidity to promote survival. The fluid also contains proteins, fructose for energy, enzymes and prostaglandins.

sensory nerve to cremaster reflex

ilioinguinal

hormone produced by sertoli cells

inhibin

female anatomical causes of infertility

Uterine conditions ○ Fibroids (noncancerous fibrous growths in the uterus) ○ Didelphys (uterine malformation where the uterus is present as a paired organ due to a failure of the Mullerian ducts to fuse. Also 2 separate cervixes and sometimes a double vagina) ○ Congenital absence of the uterus ○ Previous hysterectomy Ovarian conditions ○ Ovarian cancer ○ Ovarian torsion ○ Endometriosis → Around 30-40% of women with this are subfertile, but the link isn't completely clear. The inflammation and scarring is thought to inhibit the release of the egg or its movement through the fallopian tube. ○ PCOS (leading cause) → In PCOS, APG makes too much LH, at least double the amount of FSH, which leads theca cells to produce tonnes of androstenedione, far too much for aromatase to convert. So, the extra androstenedione flows into the blood, where some of it gets converted into estrone by aromatase in fat. Estrone feedsback to the h/thalamus and exerts negative feedback on FSH, but very large amounts of LH are still released. Thus, no single large follicle develops due to low FSH and theca cell hypertrophy, instead there are a number of smaller follicles that grow to around 10mm in size. Without the development of a dominant follicle, there is not high enough levels of oestrogen to make the switch to positive feedback and for the LH surge / ovulation to occur. Fallopian tube conditions ○ Hydrosalpinx is a distally blocked fallopian tube filled with fluid, most often caused by PID as a consequence of ascending STI infection. IVF is usually the treatment ○ Ectopic pregnancy leading to removal of the fallopian tubes, or ectopic pregnancy blocking fallopian tubes. Most common site is in the ampulla. ○ PID can cause pus and inflammation in the fallopian tubes meaning the ovum cannot reach sperm/sperm cannot reach ovum. Treatment with antibiotics to treat underlying infection ○ Occlusion due to adhesion formation from surgery, endometriosis, cancer Other ○ Clitoromegaly caused by hyperandrogenism e.g. CAH ○ Ureter duplication ○ Appendicitis ○ Transposition of the ovaries (move them out of the way to protect from radiation therapy)

blood supply to the penis

dorsal and deep penile arteries off internal pudendal artery (off internal iliac)

describe what the ectoderm, mesoderm and endoderm give rise to

ectoderm • Brain and spinal cord • PNS • Melanocytes • Epidermis/skin • Hair and nails • Lens, cornea and retina • Mouth and olfactory epithelium • Sebaceous glands mesoderm • Dermis • Gonads • Urogenital system • Kidneys • Skeletal muscle • Connective tissue, tendons and bone • Outer wall of gut • Cardiovascular system • RBCs endoderm • Pharynx • Thyroid • Trachea/bronchi • Stomach • Pancreas • Liver, bile duct and gallbladder • Gut epithelium

forms of assisted reproduction - which are established procedures which do not require approval and which are regulated activities? what are some illegal activities?

established procedures - IVF (either with your own or a donors eggs/sperm) - intrauterine donor sperm insemination - collection of eggs or sperm for donation regulated activities - preimplantation genetic diagnosis for HLA (for gender is illegal) Human leukocyte antigen (HLA) typing of embryos, so that the child's HLA matches a sick sibling, availing for cord-blood stem cell donation - donation of gametes between family members - research - embryo donation for reproductive purposes - storage of sperm from deceased man - IVF using surrogate illegal - cloning - commercial surrogacy - genetic tests for gender - implanting genetically modified gametes/embryos

motor nerve to cremaster muscle

genitofemoral

describe pre-birth circulation

• Mum → placenta → umbilical vein (oxygenated) → right and left umbilical veins • Right umbilical vein → delivers oxygenated blood to the liver lobules → deoxygenated blood → hepatic vein → inferior vena cava • Left umbilical vein → ductus venosus which connects straight to inferior vena cava (bypassing liver) • This means the IVC of the fetus is carrying both oxygenated blood which has come straight from the placenta and deoxygenated blood which has come from the liver • IVC → right atrium • Because there is no oxygen in lungs, constriction of pulmonary arteries occur due to hypoxic surroundings mean pressure builds back into right side of heart to try prevent blood flowing from right side → lungs • Therefore pressure in right atrium > left atrium and blood is shunted across through the foramen ovale. Most blood thus bypasses both the right ventricle and the lungs • Blood that does manage to get from the right atrium into the high pressure pulmonary artery is shunted straight through the ductus arteriosus into the lower pressure aorta • The blood that has gone straight through into the left atrium → left ventricle → aorta → common iliac arteries → internal/external iliac arteries • The internal iliac arteries each give rise to an umbilical artery which travel alongside the umbilical veins bringing deoxygenated blood back to the placenta where it drops off CO2 then picks up CO2

defects of GI development

• Omphalocele - ompha = umbilical cord; cele = herniation. During week 6 the intestines and other abdominal organs like the liver grow much faster than the abdominal cavity itself. The organs protrude through into the umbilical cord in a process of physiological herniation. In week 10, the abdominal cavity should be large enough so that the organs return, and if they don't then omphalocele occurs. The infant's intestines and sometimes liver protrude outside the abdomen and are covered by a thin membrane. This is surgically corrected often over several surgeries • Malrotation of gut - gut doesn't rotate properly so the small intestine and colon develop next to each other • Meckel's diverticulum - failure of the vitelline duct (remnant of the yolk sac) to close up • Hirschsprung disease - failure of enteric neurons of the gut to migrate from the neural crest. Thus, part of the gut is not innervated, affecting the passing of faeces • Urorectal fistula - incomplete Urorectal septum (fusion of anorectal canal and urogenital sinus)

physiological adaptation to pregnancy: skin

• Peripheral vasodilation increases the blood flow to the skin → spider naevi and palmar erythema • Levels of skin hormones increase promoting more excretion of natural oils. This can cause acne which is often seen in the first trimester • APG increases MSH increasing melanin levels increase causing linea nigra, a dark, pigmented, vertical line across the abdomen • Striae gravidarum, or stretch marks, are cause by elastin and collagen breakdown in the skin

most common presentations of labour

• Persistent abdominal or lower back pain • A gush or trickle of amniotic fluid • Bloody show where the mucus plug that blocks the cervix is passed • Contractions

physiological adaptation to pregnancy: endocrine

• Pituitary gland enlarges & increase in ACTH which increases cortisol and prolactin production. Note - although estrogen increases prolactin, progesterone inhibits its activity until birth. Also, the increase in cortisol can bring on pseudocushingoid symptoms, goitre can sometimes be seen • Pancreas increases insulin secretion and mother becomes more resistant due to placental lactogen - mum takes up less glucose so it can go to baby • hCG acts on the thyroid gland to slightly increase its activity (to increase BMR) resulting in a borderline low TSH (subclinical hyperthyroidism). Estrogen increases amount of thyroid binding globulin which will make it sometimes appear as if there are higher levels of thyroid hormone, while the active or free thyroid will remain the same.

physiological adaptation to pregnancy: musculoskeletal system

• Relaxin hormone secreted by placenta levels rise → ↑ mobility in pubic symphysis and sacroiliac joint • Progression of lordosis as the centre of gravity shifts which may cause lower back pain, especially in late pregnancy

Describe the changes that occur in the birth canal (uterus and vagina) in preparation for labour

• Softening and effacement of the cervix • Dilatation of the cervix • Increase in formation of myometrial gap junctions and upregulation of oxytocin receptors to allow for contraction • Relaxin causes pubic symphysis to relax

What happens to fertility as women age, and why?

• The number of functional oocytes depletes and ones remaining respond less and less to LH and FSH • DNA repair mechanisms are less effective and mutations in the DNA which are incompatible with life may result • Changing hormone levels increase the vagina acidity, decreasing sperm motility and thus chance of fertilisation • Ovarian function becomes erratic releasing unpredictable amounts of oestrogen, leading to erratic and unstable levels of LH and FSH which drive ovulation • With lifetime exposure to STIs, pregnancies and other conditions such as endometriosis, fibrosis, scarring and scriptures on the uterus accumulate

physiological adaptation to pregnancy: cardiovascular system

• Uterus expansion pushes up diaphragm which displaces apex beat more to the left and into the 4th intercostal space • Oestrogen increases renin activity causing Na+ and water retention. This increases plasma volume and although there is also an increase in RBC volume, haemodilution occurs as the increase in plasma is relatively a lot larger. This may cause peripheral oedema but is protective allowing for blood loss during parturition • The increase in blood volume causes an increase in heart rate and stroke volume, and thus cardiac output, increasing blood flow to all major organs • In the kidneys, the increase in cardiac output combined with an increase in NO and prostaglandins increases renal blood flow & GFR • High progesterone levels causes vasodilation causing a decrease in TPR and lowered blood pressure • ↑ coagulation factors put the body in a hypercoagulable state, which may increase the risk of maternal DVT • ECG changes: ST flattening and T-wave inversion remember H - hypercoagulable, haemodilution, haemorrhage E - edema, estrogen, expansion of uterus A - apex beat displaced R - retention of water, renin, RBC T - TPR drops, T-wave inversion