Human Reproduction, Development and Ageing - Week 2 Lecture Notes

Female Reproduction

1. Reproductive Overview

• System is dormant until puberty; then activated via endocrine signalling.

• Primary Sex Organs (Gonads)

  • Female: Ovaries

  • Male: Testes

• Accessory organs: ducts, glands, external genitalia.

• Gametes produced

  • Female: Ovum/Oocyte

  • Male: Spermatozoon

• Steroid hormones

  • Female: $\text{Estrogens (mainly estradiol)}$ & $\text{Progesterone}$

  • Male: $\text{Testosterone}$

2. Genetic & Embryological Sex Differentiation

• Female phenotype requires two X chromosomes.

• Key genes on X direct ovarian development.

• Primary (gonadal) differentiation guides secondary (ductal & external) differentiation:

  • Without testicular hormones, Müllerian ducts persist → uterine tubes, uterus, upper vagina.

  • Wolffian ducts regress.

• Differentiation of external genitalia completed by ≈ week 12 gestation.

3. Gross Anatomy of the Female Reproductive System

• Major functions

  1. Produce & transport gametes

  2. Site of fertilisation & embryonic incubation

  3. Parturition (birth)

  4. Post-natal nurture (lactation & care)

3.1 Pelvic Ligaments

• Ovarian ligament – ovary → uterus (medial support).

• Suspensory ligament – ovary → lateral pelvic wall; carries ovarian vessels & nerves.

• Mesovarium – short peritoneal fold anchoring ovary to broad ligament.

• Broad ligament – peritoneal double fold maintaining uterine position; subdivisions: mesosalpinx, mesovarium, mesometrium.

• Round ligament – uterus (lateral cornu) → labium majus; pathway for vessels & lymphatics.

• Uterosacral & Cardinal (lateral) ligaments – support cervix/uterus posteriorly & laterally.

3.2 Uterus

• Pear-shaped hollow muscular organ.

  • Size (non-pregnant): resembles an inverted pear.

• Regions

  • Fundus – dome above uterine tube entry.

  • Body – central portion; contains uterine cavity.

  • Isthmus – narrowing between body & cervix; internal $\text{OS}$ at junction with cervical canal.

  • Cervix – projects into vagina; external $\text{OS}$ opens to vaginal fornix.

3.2.1 Wall Layers

• Perimetrium – outer serosa (visceral peritoneum).

• Myometrium – $3$ layers of smooth muscle; thickest at fundus (power for labour contractions).

• Endometrium – mucosa; two strata

  • Stratum functionalis – cyclically proliferates/degenerates; implantation site; supplied by spiral arteries.

  • Stratum basalis – permanent; regenerates functionalis; supplied by straight arteries.

3.3 Cervix

• Composition: dense connective tissue + smooth muscle.

• Epithelium

  • Endocervix: simple columnar with mucous glands.

  • Ectocervix: stratified squamous (continuous with vaginal epithelium).

  • Transformation zone (squamocolumnar junction) — site of metaplasia & cervical pathology (Pap smear target).

• Cervical mucous dynamics

  • Ovulation → watery, alkaline, permits sperm.

  • Luteal phase/Pregnancy → viscous plug; barrier to sperm & microbes.

  • During gestation, cervix contributes to fetal retention.

3.4 Vagina

• Fibromuscular tube, length ≈ $10\,\text{cm}$.

• Functions: copulatory organ, sperm receptacle, birth canal, menstrual exit.

• Wall

  • Mucosa: stratified squamous; produces glycogen → lactobacilli → acidic pH. No intrinsic glands; lubricated by cervical & vestibular secretions.

  • Muscularis: inner circular minimal; dominant outer longitudinal SM.

  • Adventitia: dense CT with abundant elastic fibres (vaginal distensibility).

• Vaginal rugae – transverse folds increasing friction & expansibility.

3.5 External Genitalia (Vulva/Pudendum)

• Mons pubis – adipose mound over symphysis pubis; pubic hair.

• Labia majora – hair-bearing skin folds; homologous to male scrotum; contain adipose & sweat/sebaceous glands.

• Labia minora – thin hairless folds; many sebaceous glands; form border of vestibule.

• Vestibule – space housing urethral & vaginal orifices; contains:

  • Paraurethral (Skene’s) glands – homologous to prostate; possible role in female ejaculation.

  • Greater vestibular (Bartholin’s) glands – mucous secretion for coital lubrication.

• Clitoris

  • Erectile organ homologous to penis; components: glans, body (corpora cavernosa), crura, bulbs of vestibule.

  • Covered by prepuce; rich innervation; engorges on sexual stimulation.

4. Uterine (Fallopian) Tubes

• Paired ducts ≈ $10\,\text{cm}$ connecting ovaries → uterus.

• Segments

  1. Infundibulum with fimbriae – captures ovulated oocyte.

  2. Ampulla – widest; site of fertilisation; ≈ $\tfrac{2}{3}$ tube length.

  3. Isthmus – narrow, thick-walled, uterine junction.

  4. Interstitial (intramural) – traverses uterine wall.

• Histology

  • Mucosa: highly folded; ciliated columnar (propulsion) + non-ciliated peg cells (secretion).

  • Muscularis: inner circular & outer longitudinal SM; peristalsis aids transport.

  • Serosa: visceral peritoneum.

5. Ovaries & Folliculogenesis

• Dimensions: $3\,\text{cm} \times 1.5\,\text{cm} \times 1\,\text{cm}$ (almond-shaped).

• Surface: Germinal epithelium (simple squamous/cuboidal).

• Tunica albuginea: dense CT capsule beneath surface.

• Internal organisation

  • Cortex: ovarian follicles embedded in stroma.

  • Medulla: vascular loose CT.

5.1 Follicular Stages

1. Primordial follicle

   • Primary oocyte (arrested $\text{Prophase I}$) + single layer of flat follicular cells.

   • Only type present before puberty.

2. Primary follicle (early)

   • Follicular cells → cuboidal; begin mitosis → multilayer granulosa (late primary).

   • Deposition of Zona pellucida (glycoprotein coat) around oocyte.

3. Secondary follicle

   • Formation of fluid-filled spaces coalescing into antrum.

   • Stromal differentiation → Theca interna (endocrine, androgen-producing) & Theca externa (fibromuscular).

4. Tertiary / Graafian (mature) follicle

   • Diameter ≈ $1\,\text{cm}$; large antrum.

   • Granulosa cells surrounding oocyte form Corona radiata; remains attached at ovulation.

5.2 Ovulation Mechanism

• Triggered mid-cycle by Surge in $LH$ (~ 10×) & rise in $FSH$.

• Steps

  1. Stigma bulges on ovarian surface.

  2. Theca externa releases collagenases; follicular wall weakens.

  3. Prostaglandin-induced vasodilation & plasma transudation ↑ follicular pressure.

  4. Follicle ruptures; secondary oocyte (metaphase II) + corona radiata expelled into peritoneal cavity toward fimbriae.

5.3 Post-Ovulation

• Corpus hemorrhagicum – temporary clot in ruptured follicle.

• Corpus luteum (CL)

  • Granulosa → Granulosa lutein cells (secrete $\text{Progesterone}$).

  • Theca interna → Theca lutein cells (produce $\text{Estrogens}$).

  • Highly vascular; termed a temporary endocrine gland.

• Outcomes

  • No fertilisation → CL degenerates $\rightarrow$ Corpus albicans (white scar); progesterone ↓.

  • Fertilisation → human chorionic gonadotropin (hCG) from trophoblast sustains CL until placental takeover.

5.4 Atresia

• Each cycle: $\approx 20–30$ follicles begin growth; usually 1 reaches ovulation.

• $\approx 99\%$ undergo follicular atresia characterised by:

  • Oocyte & granulosa degeneration.

  • Invasion/vascularisation of granulosa layer.

  • Replacement by CT; leaves atretic scar.

6. Endocrine Regulation

• Hypothalamus secretes $GnRH$ in pulsatile fashion.

  • High frequency pulses → $LH$ dominance.

  • Low frequency pulses → $FSH$ dominance.

• Anterior Pituitary (Adenohypophysis) releases:

  • $FSH$ – follicle growth; granulosa proliferation; estrogen synthesis (via aromatase).

  • $LH$ – theca androgen production; ovulation trigger; luteinisation.

• Ovarian Hormones

  • Estrogens – endometrial proliferation, secondary sex characteristics, feedback control (negative < threshold; positive > threshold).

  • Progesterone – secretory transformation of endometrium, cervical mucous thickening, thermogenic (↑ basal body temp $\approx 0.3–0.5^{\circ}\text{C}$).

  • Inhibin – selectively inhibits $FSH$.

• Feedback Loops

  1. Early/mid-follicular: moderate estrogen + inhibin → negative feedback on $FSH$.

  2. Late follicular: sustained high estrogen (> $\sim 200\,\text{pg mL}^{-1}$ for $\sim 48\,\text{h}$) → positive feedback → $LH$ surge.

  3. Luteal: progesterone + estrogen + inhibin → negative feedback, preventing additional ovulation.

7. Menstrual (Uterine) Cycle – $\approx 28\,\text{days}$

• Purpose: synchronise oocyte availability with endometrial receptivity.

• If implantation (≈ day $20–24$ receptive window) occurs, hCG rescues CL; menstruation prevented.

8. Comparative & Clinical Notes

• Uterine Morphology Across Species (illustrated)

  • Bicornuate (cow), Duplex (kangaroo), Simplex (human), etc.

• Congenital Müllerian Anomalies: didelphys, bicornuate, septate, arcuate, unicornuate – may impact fertility.

• Pap Smear targets transformation zone; early detection of cervical intraepithelial neoplasia.

• Scientific American “Women” Edition highlighted societal impact of female health research gaps.

9. Ethical, Social & Practical Implications

• Understanding female anatomy historically lagged (“The Clitoris, Uncovered”).

  • Inadequate knowledge affected sexual health, consent, and gender equity.

• Accurate education on menstrual health combats stigma and supports reproductive autonomy.

• Assisted Reproductive Technologies (ART) necessitate ethical frameworks (Week 11 focus).

10. Key Numerical & Statistical References

• Ovary size: $3 \times 1.5 \times 1\,\text{cm}$.

• Uterine tube length: $\sim 10\,\text{cm}$.

• Vagina length: $\sim 10\,\text{cm}$.

• Follicles recruited per cycle: $20–30$; ovulated: 1; $99\%$ undergo atresia.

• Estrogen positive feedback threshold: >!200\,\text{pg mL}^{-1} for $\ge 48$ h.

11. High-Yield Exam Pointers

• Be able to diagram & label uterine wall, ovarian follicle stages, hormonal feedback loops.

• Compare histology of vagina vs uterus vs uterine tube.

• Explain mechanism of cervical mucous changes and clinical fertility relevance (Billings method).

• Describe chronological events from primordial follicle activation to corpus albicans formation.

• Correlate menstrual phases with basal body temperature changes and hormonal profiles.

• Discuss why primary female differentiation is hormone-independent whereas male differentiation is hormone-dependent.