Human Reproduction — Notes

Humans reproduce sexually and are viviparous. Reproductive events: gametogenesis, insemination, fertilisation, implantation, gestation and parturition.

Testes. A pair of oval testes lies in the scrotum, outside the abdominal cavity, which keeps them 2–2.5 °C below body temperature, as needed for spermatogenesis. Each testis (about 4–5 cm long and 2–3 cm wide) has about 250 testicular lobules, each with 1–3 highly coiled seminiferous tubules.

• The tubules are lined by spermatogonia (male germ cells), which form sperms, and Sertoli cells, which provide nutrition to the germ cells.
• Outside the tubules, in the interstitial spaces, are blood vessels, immunologically competent cells and interstitial (Leydig) cells, which secrete androgens (testosterone).

Accessory ducts: seminiferous tubules → rete testis → vasa efferentia → epididymis (on the posterior surface of each testis; stores and matures sperms) → vas deferens → joined by the duct of the seminal vesicle → ejaculatory duct → urethra → urethral meatus. The urethra carries both urine and semen.

Accessory glands: paired seminal vesicles (fluid rich in fructose, calcium and certain enzymes), the prostate (milky fluid that activates sperms), and paired bulbourethral (Cowper’s) glands (mucus that lubricates the penis). Their secretions form seminal plasma; with sperms, semen.

External genitalia: the penis, made of special tissue that helps erection, with an enlarged tip, the glans penis, covered by the foreskin.

Ovaries (2–4 cm long), the primary female sex organs, produce the ovum and the ovarian hormones (estrogen and progesterone). Each is covered by a thin epithelium enclosing the ovarian stroma: a peripheral cortex and an inner medulla. The cortex contains follicles at different stages and, after ovulation, the corpus luteum.

Oviducts (fallopian tubes), about 10–12 cm long: the funnel-shaped infundibulum near the ovary with finger-like fimbriae (which help collect the ovum after ovulation), the wider ampulla (usual site of fertilisation) and the narrow isthmus, which joins the uterus.

Uterus (womb), an inverted pear-shaped organ supported by ligaments, opens into the vagina through the narrow cervix; the cervical canal and vagina form the birth canal. Its wall has three layers: outer thin perimetrium, middle thick muscular myometrium (strong contractions at delivery) and inner glandular endometrium, which undergoes cyclical changes during the menstrual cycle.

External genitalia: mons pubis, labia majora, labia minora, hymen and clitoris. (The presence or absence of a hymen is not a reliable indicator of virginity or sexual experience.)

Mammary glands: each has 15–20 mammary lobes containing clusters of cells called alveoli, which secrete milk; milk passes through mammary tubules → mammary duct → mammary ampulla → lactiferous duct opening at the nipple.

Spermatogenesis begins at puberty in the seminiferous tubules.

• Spermatogonia (2n = 46) divide by mitosis and increase in number. Some become primary spermatocytes (2n).
• A primary spermatocyte completes meiosis I to form two secondary spermatocytes (n = 23), which complete meiosis II to form four haploid spermatids.
• Spermiogenesis: spermatids are transformed into spermatozoa (sperms).
• Spermiation: sperm heads, embedded in the Sertoli cells, are finally released from the seminiferous tubules.

Hormonal control. At puberty the hypothalamus increases secretion of GnRH, which acts on the anterior pituitary to secrete LH and FSH. LH acts on the Leydig cells, stimulating synthesis and secretion of androgens, which in turn stimulate spermatogenesis. FSH acts on the Sertoli cells and stimulates secretion of factors that help spermiogenesis.

Sperm structure. A plasma membrane covers a head (elongated haploid nucleus covered anteriorly by the cap-like acrosome, filled with enzymes that help fertilisation), a neck, a middle piece with numerous mitochondria (energy for motility) and a tail. A human male ejaculates about 200–300 million sperms; for normal fertility at least 60 percent must have normal shape and size and at least 40 percent vigorous motility.

Oogenesis begins during embryonic development: a couple of million oogonia form in each foetal ovary; no more are formed after birth. They start meiosis I and are temporarily arrested as primary oocytes, each surrounded by granulosa cells: a primary follicle. Many follicles degenerate from birth to puberty, leaving 60,000–80,000 in each ovary at puberty. Primary follicles → secondary follicles (more granulosa layers and a theca) → tertiary follicles (fluid-filled antrum). The primary oocyte in the tertiary follicle completes meiosis I, an unequal division giving a large haploid secondary oocyte and a tiny first polar body. The tertiary follicle becomes the mature Graafian follicle, in which the secondary oocyte forms a new membrane, the zona pellucida. At ovulation the Graafian follicle ruptures and releases the secondary oocyte. Meiosis II is completed only after a sperm enters, forming the ovum and a second polar body.

The reproductive cycle of female primates is the menstrual cycle, repeated at an average interval of about 28/29 days. The first menstruation at puberty is menarche; cycles cease around 50 years of age (menopause). Cycles are interrupted during pregnancy and may also stop owing to stress or poor health.

• Menstrual phase (days 1–5): the endometrial lining and its blood vessels break down, forming a liquid that is discharged through the vagina. Menstruation occurs only if the released ovum is not fertilised.
• Follicular (proliferative) phase: primary follicles grow into a fully mature Graafian follicle; the endometrium regenerates by proliferation. Pituitary LH and FSH rise gradually and stimulate follicular development and secretion of estrogens by the growing follicles.
• Ovulation (about day 14): LH and FSH reach a peak in the middle of the cycle; the rapid secretion of LH (LH surge) induces rupture of the Graafian follicle and release of the ovum.
• Luteal (secretory) phase: the remaining parts of the Graafian follicle become the corpus luteum, which secretes large amounts of progesterone, essential for maintaining the endometrium for implantation and other events of pregnancy. Without fertilisation the corpus luteum degenerates, progesterone falls, the endometrium disintegrates and a new cycle begins. During pregnancy all events of the cycle stop and there is no menstruation.

Oestrous versus menstrual cycle. Non-primate mammals (cows, sheep, rats, deer, dogs, tigers) have an oestrous cycle: no menstrual bleeding, the endometrium is reabsorbed, and the female is sexually receptive only during oestrus (heat). Primates (monkeys, apes, humans) have a menstrual cycle.

During coitus, semen is released into the vagina (insemination). Motile sperms swim through the cervix and uterus and reach the ampulla, where the ovum released by the ovary is also transported. Fertilisation can occur only if ovum and sperms reach the ampulla simultaneously.

Physico-chemical events:

1. Capacitation — sperms acquire the ability to fertilise in the female tract.
2. Acrosomal reaction — enzymes (sperm lysins) released from the acrosome dissolve a path through the corona radiata and zona pellucida.
3. Contact of a sperm with the zona pellucida induces changes in the membrane (cortical reaction) that block the entry of additional sperms, ensuring that only one sperm fertilises the ovum (no polyspermy).
4. Entry of the sperm induces completion of meiosis II of the secondary oocyte: a haploid ovum and a second polar body.
5. The haploid nuclei of sperm and ovum fuse to form a diploid zygote.

Sex determination. The ovum always carries X; sperms carry X or Y (50 percent each). X sperm → XX (female); Y sperm → XY (male). The sex of the baby is determined by the father.

Cleavage and implantation. Mitotic divisions (cleavage) begin as the zygote moves through the isthmus towards the uterus, forming 2, 4, 8, 16 daughter cells called blastomeres. The embryo with 8–16 blastomeres is a morula, which continues to divide and becomes a blastocyst as it moves into the uterus. The blastomeres are arranged into an outer trophoblast and an inner cell mass attached to it. The trophoblast attaches to the endometrium; the uterine cells divide rapidly and cover the blastocyst, which becomes embedded: implantation, leading to pregnancy.

Placenta. After implantation, finger-like projections of the trophoblast, the chorionic villi, appear, surrounded by uterine tissue and maternal blood. The chorionic villi and uterine tissue become interdigitated to form the placenta, a structural and functional unit between the developing embryo (foetus) and the mother, connected to the embryo by the umbilical cord.

• Functions: supplies oxygen and nutrients; removes carbon dioxide and excretory wastes; acts as an endocrine tissue producing human chorionic gonadotropin (hCG), human placental lactogen (hPL), estrogens and progestogens; in later pregnancy relaxin is secreted by the ovary. hCG, hPL and relaxin are produced only during pregnancy; levels of estrogens, progestogens, prolactin, cortisol and thyroxine also rise.

Development. Immediately after implantation, the inner cell mass differentiates into ectoderm, mesoderm and endoderm, which give rise to all tissues and organs. The inner cell mass contains stem cells that can give rise to all tissues. Human pregnancy lasts about 9 months.

• After one month: the heart forms (first heartbeat can be heard with a stethoscope).
• End of the second month: limbs and digits develop.
• End of 12 weeks (first trimester): most major organ systems are formed; limbs and external genital organs are well developed.
• Fifth month: first movements of the foetus and appearance of hair on the head.
• End of 24 weeks (second trimester): body covered with fine hair, eyelids separate, eyelashes form.
• End of 9 months: the foetus is fully developed and ready for delivery.

Parturition (delivery) is induced by a complex neuroendocrine mechanism. Signals from the fully developed foetus and the placenta induce mild uterine contractions, the foetal ejection reflex, which triggers release of oxytocin from the maternal pituitary. Oxytocin causes stronger uterine contractions, which stimulate further oxytocin secretion (positive feedback); this continues until the baby is expelled through the birth canal, followed soon by the placenta.

Lactation. The mammary glands differentiate during pregnancy and start producing milk towards the end of pregnancy. The milk produced during the first few days of lactation is colostrum, which contains several antibodies (IgA) essential for developing resistance in the newborn. Breast-feeding during the initial period of infant growth is recommended by doctors for bringing up a healthy baby.