Physiology of Reproduction

1. Hypothalamic-Pituitary-Gonadal (HPG) Axis

• The hypothalamus secretes GnRH (Gonadotropin-releasing hormone) in a pulsatile fashion.
• GnRH acts on the anterior pituitary gonadotropes to stimulate release of LH (luteinizing hormone) and FSH (follicle-stimulating hormone) - both glycoproteins.
• LH and FSH act via cAMP second messenger systems on gonadal target cells.
• In the absence of GnRH, the pituitary secretes virtually no LH or FSH.

2. Male Reproductive Physiology

Testicular Structure and Function

• Leydig cells (interstitial cells) produce testosterone when stimulated by LH.
• Sertoli cells (inside seminiferous tubules) support spermatogenesis when stimulated by FSH and testosterone.

Spermatogenesis

1. Spermatogonia (stem cells) undergo mitosis.
2. Primary spermatocytes undergo meiosis I → secondary spermatocytes.
3. Meiosis II → spermatids, which undergo spermiogenesis to form spermatozoa.
4. The entire process takes approximately 64-74 days.

Testosterone

Male Sexual Act

• Erection: Parasympathetic (sacral S2-4) impulses cause release of nitric oxide and VIP → activates guanylyl cyclase → increased cGMP → smooth muscle relaxation in corpora cavernosa → vasodilation and engorgement.
• Emission: Sympathetic (T12-L2) impulses cause vas deferens, ampulla, prostate, and seminal vesicles to contract, propelling sperm and seminal fluid into the urethra.
• Ejaculation: Rhythmic contractions of bulbocavernosus and ischiocavernosus muscles expel semen. - Guyton & Hall, p. 1004

3. Female Reproductive Physiology

Functional Anatomy

The Menstrual Cycle (28-day reference)

Two-Cell Theory of Estrogen Synthesis

• Theca interna cells respond to LH → secrete androgens (androstenedione, testosterone)
• Granulosa cells respond to FSH → aromatize those androgens to estrogens (estradiol)

Ovarian Cycle

• Multiple primordial follicles begin to enlarge at cycle start.
• By day 6, one dominant (Graafian) follicle is selected; others undergo atretic apoptosis.
• The dominant follicle grows, fills with follicular fluid (antrum formation), and is the main source of circulating estradiol.
• Rising estradiol causes positive feedback on the pituitary → LH surge.

• The LH surge triggers follicular rupture ~9 hours after the LH peak.
• The ovum is extruded into the peritoneal cavity and picked up by the fimbriated ends of the fallopian tube.
• Minor bleeding into the peritoneal cavity may cause mittelschmerz (mid-cycle pain).
• The ovum is fertilizable for ~24 hours (lives up to 72 hours after extrusion).

• The ruptured follicle fills with blood (corpus hemorrhagicum), then granulosa/theca cells proliferate and differentiate into lipid-rich luteal cells → corpus luteum.
• Corpus luteum secretes estrogen + progesterone (dominant hormone of luteal phase).
• If no pregnancy: corpus luteum regresses → corpus albicans → hormone withdrawal → menstruation.
• If pregnancy occurs: hCG from the embryo rescues the corpus luteum, which persists until the placenta takes over steroid production (~weeks 8-12).

Hormonal Changes Across the Cycle

Uterine (Endometrial) Cycle

• Menstruation (Days 1-5): Progesterone/estrogen withdrawal → spiral artery spasm → ischemia → endometrial shedding.
• Proliferative phase (Days 6-14): Estradiol drives regrowth of endometrium, glands, stroma, and spiral arteries.
• Secretory phase (Days 15-28): Progesterone causes glands to become tortuous, glycogen-laden, and secretory; prepares endometrium for implantation.

Effects of Estrogen and Progesterone

• Proliferation of endometrium, ductal growth in breasts
• Puberty: growth spurt, epiphyseal closure, female fat distribution, breast development
• Positive feedback at high levels → LH surge
• Increases prolactin secretion
• Stimulates myometrial growth

• Maintains secretory endometrium for implantation
• Raises uterine threshold to contractile stimuli (preserves pregnancy)
• Thermogenic (raises basal body temperature - basis of rhythm method)
• Reduces quantity and elasticity of cervical mucus post-ovulation
• Stimulates lobular/alveolar development in breast

4. Puberty

• Girls: Average onset 8-13 years; estrogen drives thelarche (breast development) → adrenarche → menarche.
• Boys: Average onset 9-14 years; testosterone drives testicular enlargement → pubic hair → voice change → spermarche.

5. Fertilization and Early Pregnancy

• Fertilization typically occurs in the ampulla of the fallopian tube.
• The fertilized egg (zygote) undergoes cleavage during transport to the uterus (~3-4 days).
• Implantation occurs at days 6-10 post-fertilization in the secretory endometrium.
• The syncytiotrophoblast immediately begins secreting hCG, which maintains the corpus luteum and prevents menstruation.
• In mid-to-late pregnancy, the placenta takes over synthesis of estrogen and progesterone.
• Estrogen stimulates myometrial growth; progesterone raises the uterine contractile threshold and preserves pregnancy.

6. Indicators of Ovulation

• Basal body temperature (BBT): Rises 1-2 days after ovulation due to progesterone thermogenesis; useful retrospectively.
• Cervical mucus: Changes from ferning/elastic (follicular) to thick/non-elastic (post-ovulation).
• LH surge detection: Urine LH kits detect the surge ~24-36 hours before ovulation.
• Progesterone level: Mid-luteal progesterone >3 ng/mL confirms ovulation.

Summary Diagram of HPG Axis

Hypothalamus
    ↓ GnRH (pulsatile)
Anterior Pituitary
    ↓ LH               ↓ FSH
Leydig cells (♂)    Sertoli cells / Granulosa cells (♀)
    ↓ Testosterone      ↓ Estrogen / Progesterone
        ↑ Negative feedback (–) to hypothalamus & pituitary
        ↑ Positive feedback (+) from high estradiol → LH surge (♀)

• Guyton and Hall Textbook of Medical Physiology, pp. 1004-1010
• Ganong's Review of Medical Physiology, 26th ed., pp. 404-410
• Costanzo Physiology, 7th ed., pp. 479-482