Female Mammalian Reproductive Physiology BZO6T16

Syllabus topics (RTMNU)

• Ovaries: location, gross anatomy and histological structure; functions in oogenesis and hormone secretion; structure and functions of uterine (fallopian) tubes in ovum transport and fertilisation
• Uterus: anatomy and histological organisation; structural layers and their significance in implantation and pregnancy
• Cervix, vagina and vulva: structure and functions; roles in reproduction and parturition
• Mammary gland: structure and histology; physiological role in lactation and neonatal nutrition

Ovaries — location, anatomy, histology and functions

Location and gross anatomy: a pair of almond-shaped organs (about 3 × 2 × 1 cm in women) in the pelvic cavity on either side of the uterus, held by the mesovarium, ovarian ligament and suspensory ligament (which carries ovarian vessels).

Histology:

• Germinal epithelium — a single layer of cuboidal cells covering the surface (a misnomer; it does not form germ cells).
• Tunica albuginea — dense connective tissue beneath it.
• Cortex — stroma containing follicles at all stages (primordial, primary, secondary, Graafian), corpus luteum and corpus albicans, atretic follicles.
• Medulla — loose connective tissue with blood vessels, lymphatics and nerves.

Functions: (1) oogenesis — production and release of ova (ovulation); (2) endocrine — oestrogens (from granulosa and theca cells of follicles), progesterone (from corpus luteum), inhibin, relaxin and small amounts of androgens.

Uterine (fallopian) tubes

Paired tubes about 10–12 cm long from the ovary to the uterus. Parts: infundibulum with finger-like fimbriae near the ovary, ampulla (widest part — usual site of fertilisation), isthmus, and intramural part. Wall: mucosa of ciliated and secretory (peg) columnar cells, smooth muscle layer, serosa.

Functions: fimbriae sweep the ovulated oocyte into the tube; cilia and peristalsis transport ovum and early embryo towards the uterus (about 3–4 days); secretions nourish gametes and help sperm capacitation; site of fertilisation and early cleavage. Implantation in the tube = ectopic pregnancy.

Uterus — anatomy and histological layers

A hollow, pear-shaped muscular organ (about 7.5 × 5 × 2.5 cm in nulliparous women) between bladder and rectum, usually anteverted and anteflexed. Parts: fundus, body and cervix. In other mammals: duplex (rabbit), bicornuate (cow, pig), bipartite (cat), simplex (primates).

• Perimetrium — outer serous coat (peritoneum).
• Myometrium — thick layers of smooth muscle; contracts strongly during labour under oxytocin.
• Endometrium — inner mucosa with simple columnar epithelium, uterine glands and stroma; stratum functionalis (thickens each cycle and is shed in menstruation) and stratum basalis (regenerates the functional layer); spiral arteries.

Significance: receives and nourishes the blastocyst; the secretory endometrium allows implantation and forms the decidua and maternal part of the placenta; myometrium stretches to accommodate the foetus and expels it at birth.

Cervix, vagina and vulva

• Cervix: narrow lower part of uterus (about 2.5 cm) projecting into the vagina; canal with internal and external os; mucous glands secrete cervical mucus — thin and watery at ovulation (helps sperm entry), thick under progesterone (mucus plug in pregnancy blocks infection). Softens, effaces and dilates (to about 10 cm) during labour.
• Vagina: fibromuscular tube (about 8–10 cm) from cervix to vestibule; lined by non-keratinised stratified squamous epithelium rich in glycogen, which lactobacilli convert to lactic acid (acidic pH about 4 — protection). Receives the penis and semen in copulation, forms the birth canal and passage for menstrual flow. Vaginal smear changes reflect the oestrous cycle in rodents.
• Vulva (external genitalia): mons pubis, labia majora and minora, clitoris (erectile, homologous to penis), vestibule with urethral and vaginal openings, hymen, and Bartholin's (greater vestibular) glands secreting lubricating mucus. Protects internal organs and has a role in sexual arousal.

Mammary glands — structure and role in lactation

Modified apocrine sweat glands — a diagnostic mammalian feature. Each breast has 15–20 lobes separated by fat and connective tissue (Cooper's ligaments); each lobe has lobules of alveoli (acini) lined by milk-secreting cuboidal cells and surrounded by contractile myoepithelial cells. Alveoli drain into ductules → lactiferous ducts → lactiferous sinuses (ampullae) → openings on the nipple, surrounded by pigmented areola with Montgomery's glands.

Hormonal control: oestrogen (duct growth), progesterone (alveolar growth), and in pregnancy hPL and prolactin develop the gland; after birth, fall in progesterone allows prolactin to start milk secretion (lactogenesis); suckling stimulates prolactin (production) and oxytocin (milk ejection / let-down reflex by contraction of myoepithelial cells).

Neonatal nutrition: colostrum (first 2–4 days) — yellowish, rich in proteins, IgA antibodies and leucocytes, low in fat; gives passive immunity. Mature milk supplies water, lactose, fat, casein and whey proteins, vitamins, minerals, enzymes and growth factors; easily digestible; protects against infections; promotes mother–child bonding; lactational amenorrhoea delays ovulation. WHO recommends exclusive breastfeeding for the first 6 months.

Likely exam questions

1. (Long, 8 marks) Describe the histological structure and functions of the mammalian ovary.
2. (Long, 8 marks) Describe the structure of the mammary gland and explain the hormonal control of lactation.
3. (Short, 4 marks) Write the structure and functions of the fallopian tube.
4. (Short, 4 marks) Describe the layers of the uterine wall.
5. (Short, 4 marks) What is colostrum? Give its importance.

Syllabus topics (RTMNU)

• Oogenesis and folliculogenesis: process of oogenesis; stages of follicular development and ovulation
• Oocyte maturation: development from primary follicle to Graafian follicle; structural and hormonal changes
• Phases of female reproductive cycle: menstrual cycle phases
• Hormonal regulation: role of GnRH, FSH, LH, oestrogen and progesterone

Oogenesis

Oogenesis is the formation of a mature ovum in the ovary.

1. Multiplication phase (in foetal life): primordial germ cells reach the ovary and become oogonia (2n), which divide by mitosis — about 6–7 million by the 5th month of foetal life.
2. Growth phase: oogonia enlarge into primary oocytes (2n), which enter meiosis I and are arrested in prophase I (diplotene/dictyotene) before birth; each is surrounded by flat follicle cells (primordial follicle). About 1–2 million at birth, about 3–4 lakh at puberty; only about 400–450 are ovulated in a woman's life; the rest degenerate (atresia).
3. Maturation phase (from puberty, one per cycle): just before ovulation (LH surge) the primary oocyte completes meiosis I, giving a large secondary oocyte (n) and a small first polar body. Meiosis II starts and is arrested at metaphase II; the secondary oocyte is ovulated. Meiosis II is completed only if a sperm enters, forming the ovum and a second polar body.

Result: one primary oocyte → one functional ovum + 2–3 polar bodies (unequal cytokinesis conserves cytoplasm/yolk for the egg). Contrast: spermatogenesis gives four sperms per spermatocyte, continuously from puberty.

Folliculogenesis and oocyte maturation — primary to Graafian follicle

Hormonal changes: two-cell, two-gonadotropin model — LH stimulates theca interna cells to make androgens (androstenedione); FSH stimulates granulosa cells to convert them to oestradiol by aromatase. Rising oestrogen from the dominant follicle causes positive feedback → LH surge.

Ovulation: about 10–12 hours after the LH peak (about day 14 of a 28-day cycle), proteolytic enzymes and prostaglandins weaken the follicle wall at the stigma; the follicle ruptures and releases the secondary oocyte with corona radiata and follicular fluid. The remaining follicle becomes the corpus luteum (granulosa-lutein and theca-lutein cells, yellow pigment lutein), which secretes progesterone and oestrogen; without pregnancy it degenerates into the white corpus albicans after about 10–14 days.

Phases of the female reproductive (menstrual) cycle

Primates show a menstrual cycle (average 28 days, from menarche at about 12–13 years to menopause at about 45–50 years); non-primate mammals show an oestrous cycle (pro-oestrus, oestrus — "heat", met-oestrus, di-oestrus, anoestrus) without menstrual bleeding.

1. Menstrual phase (days 1–5): fall in progesterone and oestrogen after regression of corpus luteum causes spiral arteries to constrict; stratum functionalis breaks down and is shed with blood (about 30–80 ml).
2. Proliferative (follicular) phase (days 6–13): FSH stimulates follicle growth; rising oestrogen repairs and thickens the endometrium, glands lengthen, spiral arteries grow; cervical mucus becomes thin and stretchy.
3. Ovulation (about day 14): triggered by LH surge; slight rise in basal body temperature afterwards.
4. Secretory (luteal) phase (days 15–28): corpus luteum secretes progesterone and oestrogen; endometrium becomes thick, oedematous, glands coiled and secrete glycogen-rich "uterine milk" — ready for implantation. If no fertilisation, corpus luteum degenerates and menstruation follows; if pregnancy occurs, hCG from the embryo maintains the corpus luteum.

Hormonal regulation of the female reproductive cycle

• GnRH (gonadotropin-releasing hormone) from the hypothalamus, released in pulses, stimulates the anterior pituitary.
• FSH (follicle stimulating hormone): growth of follicles, proliferation of granulosa cells, aromatase activity (oestrogen synthesis), LH receptor induction.
• LH (luteinising hormone): theca androgen production; the mid-cycle LH surge causes completion of meiosis I, ovulation and formation of the corpus luteum (luteinisation); maintains corpus luteum.
• Oestrogen (mainly oestradiol): proliferation of endometrium, secondary sexual characters, thin cervical mucus; negative feedback on GnRH/FSH at low levels, positive feedback at high sustained levels (about 200 pg/ml for 2 days) causing the LH surge.
• Progesterone: secretory changes of endometrium, thick cervical mucus, rise in body temperature, breast development; negative feedback on GnRH and LH (prevents new ovulation in the luteal phase and in pregnancy).
• Inhibin (granulosa cells) selectively inhibits FSH.

Likely exam questions

1. (Long, 8 marks) Describe the process of oogenesis in mammals. Add a note on the structure of the Graafian follicle.
2. (Long, 8 marks) Describe the phases of the menstrual cycle and their hormonal regulation.
3. (Short, 4 marks) What is the LH surge? Give its significance.
4. (Short, 4 marks) Write a note on the corpus luteum.
5. (Short, 4 marks) Distinguish between oestrous and menstrual cycles.

Syllabus topics (RTMNU)

• Prenatal development: fertilisation, cleavage, implantation and early embryonic development
• Placental development and pregnancy: structure and functions of placenta; three trimesters; labour and parturition
• Birth control methods: surgical sterilisation and hormonal methods; mechanism and effectiveness
• Barrier methods and medical termination: intra-uterine devices, spermicides, barrier methods and abortion

Prenatal development — fertilisation, cleavage, implantation, early embryo

Fertilisation (in the ampulla of the fallopian tube, within about 24 hours of ovulation):

1. Capacitation of sperm in the female tract (removal of glycoprotein coat, increased motility; about 5–7 hours).
2. Sperm passes through the corona radiata (hyaluronidase) and binds ZP3 of the zona pellucida → acrosome reaction releases acrosin to digest a path.
3. Fusion of sperm and oocyte membranes; cortical reaction (cortical granules release enzymes that harden the zona — block to polyspermy).
4. Secondary oocyte completes meiosis II (second polar body); male and female pronuclei form and fuse (amphimixis) → diploid zygote; sex is decided by the sperm (X or Y).

Cleavage: rapid mitotic divisions without growth while the zygote moves down the tube — 2-cell (about 30 hours), 4-cell, 8-cell, 16–32 cell morula (day 3–4; compaction). Fluid enters to form a blastocyst (day 4–5) — outer trophoblast (forms placenta/chorion), inner cell mass (embryoblast, forms embryo) and a cavity (blastocoel). Cleavage in mammals is holoblastic, nearly equal and rotational.

Implantation (about day 6–7, completed by day 10–12): blastocyst "hatches" from the zona pellucida and attaches to the secretory endometrium (usually posterior wall of the uterus) by the embryonic pole; trophoblast differentiates into cytotrophoblast and invasive syncytiotrophoblast, which erodes the endometrium and maternal capillaries; the endometrium undergoes the decidual reaction; syncytiotrophoblast begins secreting hCG.

Early embryonic development: inner cell mass forms a bilaminar disc (epiblast and hypoblast) in week 2, with amniotic cavity and yolk sac; gastrulation in week 3 (primitive streak) forms three germ layers — ectoderm (skin, nervous system), mesoderm (muscle, bone, blood, heart, kidneys, gonads), endoderm (gut lining, liver, lungs); notochord and neurulation (neural tube); somites; heart begins to beat around day 22; organogenesis during weeks 3–8 (embryonic period — most sensitive to teratogens); foetal period from week 9 to birth.

Placenta — structure and functions

The placenta is the intimate connection between foetal and maternal tissues for physiological exchange. In humans it is discoidal, haemochorial (chorionic villi bathed directly in maternal blood) and deciduate; at term about 15–20 cm in diameter, 2–3 cm thick and 500 g. Other mammals: diffuse epitheliochorial (pig, horse), cotyledonary syndesmochorial (cow, sheep), zonary endotheliochorial (dog, cat).

• Foetal part: chorion frondosum with branched chorionic villi containing foetal capillaries (from umbilical vessels); maternal part: decidua basalis; intervillous spaces filled with maternal blood from spiral arteries; divided into 15–20 cotyledons by septa. Connected to the foetus by the umbilical cord (two arteries, one vein in Wharton's jelly).
• Maternal and foetal blood do not mix; the placental barrier (syncytiotrophoblast, cytotrophoblast, connective tissue, capillary endothelium) becomes thinner as pregnancy advances.

Functions: respiration (O₂ to foetus, CO₂ away), nutrition (glucose, amino acids, fatty acids, vitamins, minerals), excretion (urea, uric acid, creatinine), endocrine (hCG, oestrogens, progesterone, hPL, relaxin, CRH), protection (passes IgG antibodies — passive immunity; partial barrier to microbes, though rubella virus, HIV, Treponema, many drugs and alcohol can cross), storage (glycogen, iron).

Stages of pregnancy, labour and parturition

Human gestation lasts about 40 weeks (280 days) from the first day of the last menstrual period (about 38 weeks from fertilisation), divided into three trimesters:

• First trimester (weeks 1–12): implantation, embryonic period, organogenesis; heartbeat; high hCG — morning sickness; highest risk from teratogens and miscarriage.
• Second trimester (weeks 13–27): rapid foetal growth, movements felt ("quickening" about 18–20 weeks), lanugo hair, sex distinguishable; placenta takes over hormone production.
• Third trimester (weeks 28–40): weight gain, fat deposition, lung maturation (surfactant), descent of the head into pelvis.

Labour (parturition): triggered by foetal signals (foetal cortisol), rise in the oestrogen:progesterone ratio, increased oxytocin receptors, prostaglandins and stretch of the uterus. Ferguson reflex — cervical stretch → more oxytocin → stronger contractions (positive feedback). Relaxin softens the cervix and pelvic ligaments. Stages: (1) dilatation of cervix to 10 cm (longest), rupture of membranes; (2) expulsion of the baby; (3) placental (after-birth) stage — expulsion of placenta and contraction of uterus to stop bleeding.

Birth control methods — surgical sterilisation and hormonal methods

• Surgical sterilisation (permanent): tubectomy (tubal ligation — fallopian tubes cut and tied or blocked by rings/clips, laparoscopically) prevents ova meeting sperm; vasectomy — vasa deferentia cut and tied (no-scalpel technique), sperm absent from semen after about 3 months; effectiveness more than 99%; reversal difficult.
• Hormonal methods: combined oral contraceptive pills (synthetic oestrogen + progestin, e.g. Mala-D) — suppress FSH/LH, so no follicle growth or ovulation; also thicken cervical mucus and make endometrium unsuitable; progestin-only pills; Saheli (centchroman/ormeloxifene — non-steroidal, weekly pill, developed by CDRI Lucknow); injectables (DMPA, 3-monthly), implants under the skin (3–5 years), vaginal rings and patches; emergency contraceptive pill (levonorgestrel within 72 hours of unprotected intercourse). With correct use effectiveness above 99% (typical use lower, about 91–93% for pills).

IUDs, spermicides, barrier methods and medical termination

• Intra-uterine devices (IUDs): inserted into the uterus by a doctor — non-medicated (Lippes loop), copper-releasing (CuT-380A, Multiload-375 — Cu ions reduce sperm motility and fertilising capacity), hormone-releasing (LNG-IUS, Progestasert — thicken cervical mucus, make uterus unsuitable). They increase phagocytosis of sperm and prevent implantation; effectiveness about 99%; can last 5–10 years; side effects — bleeding, pain, expulsion.
• Spermicides: chemicals such as nonoxynol-9 in foams, jellies, creams and vaginal tablets that kill sperm; used with barrier methods; low effectiveness alone.
• Barrier methods: male condom (also protects against STIs including HIV), female condom, diaphragm, cervical cap and vault (cover cervix, reusable, used with spermicide), contraceptive sponge — prevent sperm from reaching the ovum.
• Medical termination of pregnancy (abortion): intentional ending of pregnancy before full term. Methods: medical — mifepristone (anti-progesterone) followed by misoprostol (prostaglandin) in early pregnancy; surgical — manual/electric vacuum aspiration, dilatation and evacuation. In India it is legal under the MTP Act, 1971 (amended 2021): up to 20 weeks on one registered doctor's opinion, 20–24 weeks for special categories (e.g. rape survivors, minors) on two doctors' opinion, and beyond 24 weeks only for substantial foetal abnormalities on a Medical Board's approval — check latest. Sex-selective abortion is a crime under the PCPNDT Act, 1994.

Likely exam questions

1. (Long, 8 marks) Describe fertilisation, cleavage and implantation in humans.
2. (Long, 8 marks) Describe the structure and functions of the human placenta.
3. (Short, 4 marks) Explain the mechanism of action of oral contraceptive pills.
4. (Short, 4 marks) Write a note on intra-uterine devices.
5. (Short, 4 marks) What are the stages of labour?

Syllabus topics (RTMNU)

• Teratogens and their effects: effects of chemicals, drugs and radiation on foetal development
• Prenatal diagnostic techniques: foetal ultrasonography, amniocentesis, chorionic villus sampling, non-invasive prenatal test
• Hormones of pregnancy: sources and functions
• Early pregnancy tests: principle and application of hCG-based tests

Teratogens and their effects

Teratogens are agents that cause structural or functional abnormalities (birth defects) in the developing embryo/foetus. Effects depend on the dose, the genotype and especially the timing: weeks 1–2 — "all or none" (embryo dies or recovers); weeks 3–8 (organogenesis) — most sensitive, major malformations; foetal period — growth retardation and functional defects (brain).

Prevention: avoid alcohol, smoking and unnecessary drugs/X-rays; rubella vaccination before pregnancy; folic acid supplements (to prevent neural tube defects); good diabetes control; avoid exposure to chemicals.

Prenatal diagnostic techniques

• Foetal ultrasonography: high-frequency sound waves (about 2–10 MHz) are sent through the abdomen (or vagina) and the reflected echoes form a real-time image. Non-invasive and safe (no ionising radiation). Uses: confirm and date pregnancy, number of foetuses, foetal heartbeat, growth, position, placental location, amniotic fluid volume; anomaly scan at about 18–20 weeks for structural defects; nuchal translucency at 11–14 weeks (marker for Down syndrome); Doppler for blood flow; guiding amniocentesis and CVS.
• Amniocentesis: at about 15–20 weeks, a fine needle is passed through the abdominal wall into the amniotic sac under ultrasound guidance and about 15–20 ml of amniotic fluid is withdrawn. Foetal cells in it are cultured for karyotyping (Down syndrome — trisomy 21, other chromosomal disorders), DNA and biochemical tests (inborn errors of metabolism, sickle-cell, thalassaemia), and fluid α-fetoprotein (raised in neural tube defects). Risk of miscarriage is small (well under 1%); results take 1–3 weeks.
• Chorionic villus sampling (CVS): at about 10–13 weeks, a small sample of chorionic villi (placental tissue of foetal origin) is taken through the cervix (transcervical catheter) or abdomen under ultrasound guidance. Gives earlier results (cells divide rapidly, no culture needed) for chromosomal and genetic disorders; slightly higher miscarriage risk than amniocentesis; possible mosaicism.
• Non-invasive prenatal test (NIPT): after about 10 weeks, a maternal blood sample is analysed for cell-free foetal DNA (from the placenta) by next-generation sequencing to screen for trisomies 21, 18, 13 and sex chromosome abnormalities. No risk to the foetus; high sensitivity, but it is a screening test — positive results are confirmed by amniocentesis or CVS. Older maternal serum screening (double, triple, quadruple marker tests) works on a similar principle.

In India, the PCPNDT Act, 1994 permits prenatal diagnosis only for detecting abnormalities and strictly bans determination or disclosure of the sex of the foetus.

Hormones of pregnancy — sources and functions

Early pregnancy tests based on hCG

Principle: hCG is produced only by trophoblast tissue, appears in maternal blood about 8–10 days after fertilisation and in urine soon after, roughly doubling every 2–3 days in early pregnancy. Tests detect its β-subunit (specific to hCG, unlike the α-subunit shared with LH, FSH, TSH) using antibodies.

• Old biological tests: Aschheim–Zondek test (mouse), Friedman test (rabbit), frog/toad test — injecting urine caused ovulation or sperm release in the animal (historical).
• Immunological tests: earlier latex agglutination-inhibition tests; now immunochromatographic (lateral flow) "pregnancy kit" strips — a sandwich ELISA principle: urine moves along the strip; hCG binds mobile coloured (gold-labelled) anti-β-hCG antibodies; the complex is captured by fixed antibodies at the test line, producing a coloured band; a control line confirms the strip works. Two lines = positive. Sensitive to about 20–25 mIU/ml — positive around the time of the missed period; morning urine is best.
• Serum β-hCG test (quantitative ELISA/chemiluminescence): detects pregnancy earlier (about 8–11 days after conception) and measures the level to monitor early pregnancy, ectopic pregnancy, miscarriage and molar pregnancy/choriocarcinoma (very high hCG).

Applications: early confirmation of pregnancy for antenatal care, timely avoidance of teratogens, diagnosis of ectopic pregnancy and trophoblastic tumours. False positives may occur with hCG injections or trophoblastic disease; false negatives if tested too early or with dilute urine.

Likely exam questions

1. (Long, 8 marks) What are teratogens? Describe the effects of chemicals, drugs and radiation on foetal development.
2. (Long, 8 marks) Describe the principle and applications of amniocentesis, chorionic villus sampling and non-invasive prenatal testing.
3. (Short, 4 marks) Write the sources and functions of hCG.
4. (Short, 4 marks) Explain the principle of the home pregnancy test kit.
5. (Short, 4 marks) Write a note on foetal ultrasonography.