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PY9.1-10 | Reproductive Physiology — Part 2

Spermatogenesis: Making 300 Million Sperm a Day

Spermatogenesis is the process of sperm production in the seminiferous tubules. It begins at puberty and continues throughout life, producing approximately 300 million sperm per day.

Figure: Spermatogenesis: Making 300 Million Sperm a Day

The seminiferous tubule has two cell types:
1. Sertoli cells — the "nursing" cells. They support developing sperm, produce AMH, secrete inhibin (feeds back to inhibit FSH), and form the blood-testis barrier (protects developing sperm from immune attack).
2. Spermatogonia — the germ cells that undergo spermatogenesis.

Steps of spermatogenesis (takes ~74 days in total):
1. Spermatogonia (diploid, 2n) → mitosis → maintain the stem cell pool and produce primary spermatocytes
2. Primary spermatocytes → meiosis I → two secondary spermatocytes (haploid, n)
3. Secondary spermatocytes → meiosis II → four spermatids (haploid, n)
4. Spermiogenesis — spermatids transform into spermatozoa (mature sperm): nucleus condenses, tail (flagellum) forms, acrosome (contains enzymes for egg penetration) develops
5. Spermiation — mature sperm released into tubular lumen
6. Final maturation occurs in the epididymis (sperm gain motility here)

Sperm structure (mnemonic: HMT — Head, Midpiece, Tail):
• Head — contains condensed nucleus + acrosome (enzyme cap for fertilisation)
• Midpiece — packed with mitochondria (ATP for motility)
• Tail — flagellum for forward propulsion

Hormone regulation of spermatogenesis:
• FSH → acts on Sertoli cells → promotes spermatogenesis and inhibin production
• LH → acts on Leydig cells → stimulates testosterone production
• Testosterone (high local concentration in testis) → essential for spermatogenesis at all stages
• Inhibin → negative feedback on FSH (not LH)
• Testosterone → negative feedback on both LH and GnRH

Testosterone: Functions and Regulation

Testosterone is an androgenic steroid hormone synthesised from cholesterol in the Leydig cells of the testes. It is the principal male sex hormone.

Figure: Testosterone: Functions and Regulation

Functions of testosterone:
• During embryonic development: virilisation of the Wolffian ducts and external genitalia
• At puberty: drives all secondary sexual characteristics — testicular growth, penile growth, deepening voice (laryngeal growth), pubic/axillary/facial hair, muscle mass, bone density, libido
• In adulthood: maintains libido, muscle mass, bone density, erythropoiesis (stimulates EPO production → higher RBC count in males), spermatogenesis
• Anabolic effects: promotes protein synthesis and nitrogen retention in muscle

Testosterone metabolism:
• In some target tissues, testosterone is converted to dihydrotestosterone (DHT) by the enzyme 5α-reductase. DHT is more potent than testosterone and acts on prostate, hair follicles, and external genitalia.
• In adipose tissue and brain, testosterone is aromatised to oestradiol (also important in males for bone health and libido).

Regulation — The HPG axis negative feedback:
`
Hypothalamus: GnRH (pulsatile)
↓
Anterior Pituitary: LH + FSH
↓
Leydig cells: Testosterone Sertoli cells: Inhibin
↓ ↓
Negative feedback to Negative feedback to
Hypothalamus + Pituitary Pituitary (FSH only)
`

• High testosterone → suppresses GnRH and LH (long-loop feedback)
• This is the principle behind anabolic steroid abuse: exogenous testosterone suppresses LH → Leydig cells atrophy → testes shrink → spermatogenesis fails → infertility

Female Reproductive System: Anatomy and Hormones

The female reproductive system performs three integrated functions: produce eggs (oogenesis), receive and transport sperm, and support pregnancy. Its anatomy is designed around these roles.

Figure: Female Reproductive System: Anatomy and Hormones

Key structures:
• Ovaries — paired almond-shaped organs (3 cm). They produce oocytes (eggs), oestrogen, progesterone, and inhibin. Each ovary contains ≈200,000 primordial follicles at puberty (from ~2 million at birth).
• Fallopian tubes — muscular tubes connecting ovaries to the uterus. Site of fertilisation (typically in the ampulla). Ciliated epithelium moves the egg toward the uterus. Tubal ligation cuts or blocks here as a permanent contraceptive method.
• Uterus — pear-shaped muscular organ. Layers: perimetrium (outer serous layer), myometrium (muscular — contracts during menstruation and labour), endometrium (inner lining — proliferates and sheds cyclically).
• Cervix — lower narrow part of uterus. Cervical mucus changes across the cycle (thin and stretchy at ovulation, thick and impermeable after).
• Vagina — fibromuscular canal. Site of sperm deposition during intercourse. Acidic pH (3.5–4.5) protects against infection but is hostile to sperm → cervical mucus at ovulation provides a protective channel.

Oestrogen — Functions:
• Development of female secondary sexual characteristics at puberty
• Proliferative effect on the endometrium (builds it up in the first half of the cycle)
• Induces the LH surge (positive feedback) mid-cycle → triggers ovulation
• Maintains bone density (anti-osteoporotic)
• Reduces LDL, increases HDL cholesterol (hence pre-menopausal protection against atherosclerosis)
• Promotes vaginal lubrication and epithelial health
• Negative feedback on FSH + LH (long-loop, at low levels)

Progesterone — Functions:
• Produced mainly by the corpus luteum after ovulation (and later by the placenta in pregnancy)
• Converts proliferative endometrium → secretory endometrium (prepares for implantation)
• Inhibits uterine contractions — critical for maintaining pregnancy
• Increases basal body temperature by 0.5°C (used in natural family planning)
• Thickens cervical mucus → impermeable to sperm (basis of progestogen-only pill)
• Negative feedback on LH + GnRH