RDA

Question 1

Describe the male reproductive tract.

Answer 1

Regulatory hormones 
• Gonadotrophin releasing hormone (GnRH)
– Hypothalamus 
• Luteinising hormone (LH)
– Anterior pituitary 
• Follicle stimulating hormone (FSH)
– Anterior pituitary 
• Testosterone (T)
- Testis 

• Testis – contain seminiferous tubules (to produce sperm) and Leydig cells which produce testosterone.
• Epididymis – one within each scrotal sac. Sperm are stored in these and at ejaculation, sperm pass through the vas deferens (contractile) and are mixed with fluid from the seminal vesicles. The fluid then leaves the duct and passes into the urethra to mix with prostate secretions.
• Leydig cells – testosterone – LH stimulated.
• Sertoli cells – Inhibin – FSH stimulated.

Spermatogenesis

1. Germ cells 44+XY (diploid).
   a. Mitotic division.
2. Primary spermatocyte 44+XY (diploid).
   a. 1st meiotic division.
3. Secondary spermatocyte 22+X, 22+Y (haploid).
   a. 2nd meiotic division.
4. Spermatids 22+X, 22+Y (haploid).
5. Spermatozoa 22+X, 22+Y (haploid).

200m sperm/day, starts at puberty.

Male reproductive function
• Starts at puberty 
• Functions continually 
• Normally continues throughout the rest of life 
• Sperm quantity and quality generally
decreases with increasing age 
• LH stimulates testosterone production 
• FSH and testosterone sustain Sertoli cell
function 
• Sertoli cells support spermatogenesis

Question 2

Describe the female reproductive system.

Answer 2

Female reproductive function
• Starts at puberty
• Functions cyclically
• Normally operates until ~45 years of age
• Egg quality generally decreases with
increasing age
• FSH stimulates (some) development of ovarian follicles & 17b-estradiol synthesis
• LH stimulates progesterone production
• The steroids regulate uterine endometrium

The ovary – produce the gametes and steroids (oestrogens and progesterone’s).
The fallopian tubes – oviduct – sustains oocyte or conceptus.
Uterus – conceptus implants here.

Female Ovary

• Many follicles do not develop all the way to ovulation; many undergo atresia.
• Thecal cells – oestrogen and androgens – LH.
• Granulosa cells – androgens —> oestradiol (produce progesterone in the second-half of the cycle) – FSH.

Progestogens – maintain endometrium.
Oestrogens – stimulate proliferation of the endometrium.

Question 3

Describe sexual reproduction and fertilisation.

Answer 3

Definitions

• Sexual reproduction – produce genetically different offspring.
• Sexual intercourse – required for – sexual reproduction, sexual activity, sexual pleasure, human bonding.
• Biological sex – identifies gender, a result of chromosomes, produces different gametes.

Brain Pathways

• Meso-limbic DA system – reward & pleasure pathways.
• Nigro-striatal tract – control of movements.
• Neuro-endocrine pathways – regulating fertility and parenting.

Penile erection pathways:
o Sexy thoughts in brain OR tactile stimulus to penis.
-Brain – limbic system.
o Spinal cord – efferent to penis, afferent back.
-Pudendal nerve.

Penile Erection Changes

1. (ESEED) increased PNS to SM of pudendal artery.
2. Increase activity of NOS and thus NO release.
3. NO stimulates cGMP  vasodilation.
   a. cGMP inactivated by phosphodiesterase.
4. Counteracts SNS-maintained myogenic tone.
5. Increases blood flow in corpus cavernosum.
   a. Compress dorsal vein restricting outflow of blood.
   b. Urethra not compressed due to corpus spongiosum.

Clitoral Erection Changes
Same mechanism as the penis.

Fertilisation

1. Deposition of sperm near the cervix.
   a. Cervical mucous is hostile to sperm which forms a physical barrier.
   b. Cervical mucous changes at mid-cycle to permit sperm to enter the uterus.
2. Passage of sperm through uterus and then fallopian tubes.
3. Sperm moves to fallopian tube ampulla.
   a. 2mm/min, 12cm/hour.
   b. Survival of the fittest.
   c. Capacitation takes place (within the uterus) which matures the spermatozoa.
4. Egg meets sperm fusion of egg with sperm (24 hours post ovulation).
   a. Acrosome reaction – penetration of zona pellucida (& Coronal cells).
   b. Calcium flux.
   c. Resumption of meiosis, release of 2nd polar body.
   d. Alignment of maternal and paternal chromosomes to generate zygote.
5. Change in Zona Pellucida to stop additional sperm fusing.
6. Initiation of mitotic divisions in embryo.

Fertilisation – pictures.

• Cortical reaction – hardening of zona pellucida and exclusion of other sperm.
• Picture 3 – meiosis 2 is complete in the maternal nucleus leading to a second polar body and the paternal sperm head undergoes decondensation and expands.
• Picture 4 – duplication of both DNA sets occurs to leave 2n chromosomes of both origins.

After fertilisation
• Meosis of maternal chromosomes resumes,
forming female pronucleus (23 chromatids),
and 2nd polar body.
• Sperm chromosomes decondense to form
male pronucleus (23 chromatids).
• Chromatids in both pronuclei are duplicated • They align on the mitotic spindle, and are
separated into 2 identical ‘daughter’ cells (1st
cleavage division of the embryo).

Question 4

Describe the menstrual cycle.

Answer 4

Composed of the endometrial & ovarian cycles.
o Endometrial – menstrual, repair and proliferative, secretory phases.
o Ovarian – follicular, luteal phase.
1. FSH & LH stimulate the follicular phase which results in oestradiol production —> stimulates the endometrial proliferation.
2. Oestradiol (E2) production continues at a greater pace and –ve feedback switches to +ve and ovulation occurs.
3. Corpus luteum produces progesterone and E2 and the endometrium enters the secretory phase.

Menstrual cycles last ~28 days (21-35 days).
o In younger people, it may be longer.
o Older people, shorter OR longer.
Note the change of –ve to +ve feedback of E2.

-Oestrogen dominates the proliferative or follicular phase.
-Progesterone dominates the secretory or luteal phase.
-Terminology used depends upon what is being described:
o Endometrium/Uterine – proliferative/secretory.
o Ovarian – follicular/luteal.

• Thinnest – 2-4mm.
• Thickest – 7-16mm.

Note basal body temperature raises around ovulation.

1. Gradual rise of oestradiol by developing follicle (FSH).
2. Follicles grow and –ve feedback on LH and FSH.
3. Dominant follicle selected and produces lots of E2—> –ve feedback switch to +ve feedback —>LH surge.
4. Ovulation.
5. Corpus luteum produces E2 and progesterone —> -ve feedback on LH and FSH.
6. No fertilisation —> E2 and progesterone fall and endometrium enters secretory phase.

Question 5

Describe follicugenesis.

Answer 5

1. Oogonia 44+XX (diploid).
   a. Mitotic division.
2. Primary oocytes 44+XX (diploid).
   a. 1st meiotic division.
3. Secondary oocyte (+polar body) 22+X, 22+X (haploid).
   a. 2nd meiotic division.
4. Ovum (+ polar body) 22+X, 22+X (haploid).

Note – 1st meiotic division is linked to the LH surge, meiosis 2 follows immediately after this BUT pauses in metaphase 2 (as shown).
Note – the second polar body is generated after the 2nd meiotic division which occurs in the fertilised cell.

Folliculogenesis – Important Points:
-Time taken for primordial follicle —> secondary oocyte is MORE than one month.
o The human ovary contains multiple follicles at ALL stages of development with one dominant (Graafian) follicle at any one time.
o The ovaries alternate the release as well (so each one releases one follicle each ~56 days).
-Human ovaries contain 2m primordial follicles at birth —> only 400 released at ovulation in a lifetime.
-During meiosis, both the 1st and 2nd divisions are paused during follicular development.
o Meiosis 1 starts during embryonic development, but halts at diplotene stage of prophase 1 (primary follicle) which is arrested until puberty (meiosis then resumes and 2nd follicles develop).
o 2nd follicles then undergo a second arrest.
-Key points:
o Ovaries – contain ~6m primordial follicles at ~20w development—> ~1m at delivery of infant.
-400 released over a lifetime.
o Testes – produce 100m sperm/day from puberty onwards.

Oogenesis summary
• Ovulation = release of mature oocyte (egg)
from the ovary
• Oocyte is 2n at this stage, in meiotic arrest (
metaphase II)
• Enters the Fallopian tube
• Needs to be fertilised within 24 hours, as it
degenerates after this

Question 6

Describe maternal changes in pregnancy and trimesters.

Answer 6

-Pregnancy is divided into 3 trimesters.
-Spontaneous loss of pregnancy in the first trimester is very common (1/3rd of all) but after that, loss is minimal.
-The end of the 2nd trimester marks the limit of infant survival (after this, the child is viable).
o Modern care can push this back to 22 weeks.
-Term (39-40 weeks) is expected delivery time and is stated as ~280 days (40 weeks) since LMP.

Maternal changes

• Increased weight [3rd]
• Increased blood volume [2nd & later] -Increased blood clotting tendency [2nd & later]
• Decreased blood pressure [2nd]
• Altered brain function [1st & later]
• Altered hormones [1st & later]
• Altered appetite (quantity and quality) [1st & later] – GI imbalance
• Altered fluid balance [2nd & later]
• Altered emotional state [1st & later]
• Altered joints [3rd]
• Altered immune system [1st & later]

abdominal changes in the mother only become apparent during the 2nd trimester

-Increased weight – (+10-15kg) – baby, placenta, amniotic fluid, increased fluid retention, increased stores.

-Increased hormone levels:
o hCG – peaks 1st trimester and decreases thereafter.
o All other hormones (progesterone, oestrogens, lactogen) – slowly increase as the pregnancy progresses.
-Progesterone is key to maintaining the pregnancy – progesterone antagonists  loss of pregnancy at ALL gestational ages.
• Progesterone source:
o Fertilisation —> 8 weeks’ gestation – corpus luteum source via hCG.
o 8+ weeks – placenta supplies progesterone.
-The change-over = “Luteo-placental shift”.
• Oestrogen source:
o Fertilisation —> Luteo-placental shift – corpus luteum.
o 8+ weeks – complex interplay between foetal/maternal adrenals and placenta.
-Human placenta – does not express the enzymes needed to convert pregnenolone  androgens so this occurs in foetal adrenals.
• The weak androgen produced (DHEA) is sulphated to give DHEA-S which is inactive (so female foetus is not exposed to androgens).
• DHEA-S goes to the placenta to be converted to 17B-oestradiol.

-High levels of oestriol are produced by a parallel mechanism including hydroxylation of DHEA-S in foetal liver to give 16OH-DHEA-S.

• High steroid levels supress HPG-axis —> low FSH and LH throughout.
• Increased blood clotting tendency – protective against losing blood at delivery.
• Decreased blood pressure – is lowest during 2nd trimester and is why pregnant women should not stand for long.
• Increased basal body temperature – possibly by role of progesterone. Also, mediated by increased foetal size.
• Increased breast size – changes start in 1st trimester and continue throughout – due to all hormones!
• Increased vaginal mucus – more clear mucus produced.
• “Morning sickness” – affects 80%, more severe version is “Hyperemesis gravidarium”. Unknown cause but maybe linked to hCG levels being high in the first trimester.
• Altered brain function – due to high levels of steroids, such as progesterone.
• Altered appetite – due to +height of fundus, stomach may be impinged and mother may need smaller meals.
• Altered fluid balance and urination frequency – kidney functions change  ~50%+ in plasma fluid volume by term. Increasing abdominal size also puts pressure on bladder so more frequent urination.
• Altered emotional state – due to hormone levels and can vary in people (e.g. happy  post-natal depression).
• Altered joints – changes in pelvis to make connections more flexible to permit child-birth.

-Altered immune system – 2 main points should be considered:
o Production of factors – supress the maternal immune system from the utero-placental interface. This results in a reduction of Th1 responses and increased Th2 responses.
o Placenta expresses unusual HLA – placental HLA are almost invariant (HLA-G has 5 known sequence variants – normal HLA-A and others have millions of variants) and very simple. This is thought to identify the tissue as human but due to its simplicity, no other information is given. HLA-G can also supress some leucocytes and down-regulate maternal immune responses.

The mother
• Relatively little risk in the early parts of
pregnancy
• Main risk to maternal health (or life) linked to
delivery

Question 7

Describe the foetal changes in pregnancy.

Answer 7

Pregnancy is counted from the first day of the last menstrual period (LMP), with other events dated from this time.
o This is important as an embryologist and an obstetrician would use different time-scales.
-IVF pregnancy timing – fertilisation occurs 2-3 days before:
o There will be a difference in time of 2-2.5w from the gestational age (GA, derived from LMP) and the GA in an IVF pregnancy – this can make a large difference when determining viability (22 vs 24 weeks for example).

• Conceptus – everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)
• Embryo – the baby before it is clearly
human
• Fetus – the baby for the rest of pregnancy
• Infant – less precise, normally applied after
delivery

Again, remember that timings used to discuss embryology are usually from point of fertilisation, 2 weeks after LMP timings used in timings of pregnancy – the embryology timings are PF – Post-Fertilisation.
Weights:
o First trimester – 50g.
o Second trimester – 1050g – viable at 500-820g stage (21-24 weeks).
o Third trimester – 2100g.

Regulation of Development
-Chromosomal abnormalities:
o Too few sex chromosomes – Turner’s syndrome – 45 X0.
o Too many sex chromosomes – Klienfelter’s syndrome – 47 XXX, 47 XYY, etc.
o Too few autosomes – non-viability, as does 45 Y0.
o Too many autosomes – Downs Syndrome – trisomy 21.
-Most risks to the pregnancy occur in the first trimester of pregnancy. The main risks associated with pregnancy in the 3rd trimester is to do with the birth.
o There are 4 main organs (lungs, digestive system, immune system and brain) that have limited use in utero so late development is logical but problems developing here become apparent at birth.
-This also may cause problems with pre-term birth.

Question 8

Describe the placenta.

Answer 8

Placental Functions

1. Exchange of nutrients and waste products.
2. Connection/Anchorage – the foetus is bound to the mother’s arterial blood supply.
3. Separation – despite the close contact, the foetus and the maternal vascular system must remain separated.
4. Biosynthesis – second only to the liver in the biosynthesis functions.
5. Immunoregulation – ensures no rejection of conceptus. This cannot be the function of the uterus as ectopic pregnancies outside of the uterus can still proceed.

Anatomy of the Placenta
-Primary subunit is the placental villus that has the branches.
o This provides a large surface area for exchange between the maternal and foetal vascular systems.
-Note that the veins contain oxygenated blood and the arteries contain deoxygenated blood as the placenta carries out a parallel function to the lungs during pregnancy.
-Note the separation of the maternal and foetal systems despite being near.
-Cotyledons – the maternal surface of the placenta is sub-divided into cotyledons (30-60/placenta). Each contains one or more villi.

(1) Development of the Placenta
- Approx. 9 days PF, the conceptus is completely implanted in the maternal endometrium.
- Placenta originates from the cytotrophoblasts layer.

(2) Development of the Placenta
- Cytotrophoblasts proliferate into the syncytium to form a columnar structure which becomes a villous structure.

(3) Development of the Placenta
The overall structure then does not change but it is modified.
o There are fewer cytotrophoblasts present at term so that there can be a closer apposition between the syncytium and placental capillaries.

Contact with Maternal Tissues – Macro-formation:
 Early, the conceptus is in contact with endometrial cells.
 As it grows, the conceptus makes transient contact with maternal capillaries but rapidly proliferating cytotrophoblasts cells form a capsule around the conceptus, isolating it about 4 weeks PF (2 weeks LMP GA).
o Decidual glands hypertrophy during the 1st trimester to provide nutrients for placenta and baby. The placenta functions normally but it is the source of nutrients rather than the maternal blood that is different.
 Cytotrophoblast shell (plugs) remains in place until ~8w PF (~10w GA), this blocks the spiral artery formation.
o The cytotrophoblast is still important in remodelling later though.