Reproductive Physiology

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Reproductive Physiology — Key Facts for NEET PG

• Sertoli cells: Support spermatogenesis, secrete inhibin (↓ FSH), produce ABP (binds testosterone)
• Leydig cells: Produce testosterone under LH stimulation; synthesize via cholesterol → pregnenolone → testosterone
• Oocyte development: Primordial → primary → secondary (ovulation) → ovum (fertilization); arrested at metaphase II until fertilization
• FSH/LH: FSH stimulates follicular development (granulosa cells) and spermatogenesis (Sertoli cells); LH stimulates theca cells (androgen synthesis) and ovulation/luteinization
• ⚡ Exam tip: Inhibin B (from Sertoli cells in males) is the best marker of spermatogenic function; Inhibin A (from corpus luteum in females) regulates follicular phase

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Reproductive Physiology — NEET PG Study Guide

Male Reproductive System

Testis Structure:

• Seminiferous tubules: Spermatogenesis (spermatogonia → spermatozoa)
• Interstitial space: Leydig cells (testosterone), blood vessels
• Rete testis: Collects sperm
• Efferent ductules: Connect to epididymis

Spermatogenesis (takes ~74 days):

Cell Type	Stage
Spermatogonia (A and B)	Sperm stem cells
Primary spermatocytes	Undergo meiosis I
Secondary spermatocytes	Undergo meiosis II
Spermatids	Haploid cells
Spermatozoa	Differentiated sperm

Sertoli Cell Functions:

• Nurse cells: Support and nourish developing sperm
• Blood-testis barrier: Tight junctions between Sertoli cells
• ABP (Androgen-Binding Protein): Maintains high testosterone in seminiferous tubules
• Inhibin: Inhibits FSH release from pituitary
• Anti-Müllerian Hormone (AMH): Causes regression of Müllerian ducts in fetus

⚡ Exam tip: Klinefelter syndrome (47,XXY): Tall stature, small firm testes, gynecomastia, azoospermia, ↑ FSH/LH; Primary testicular failure

Leydig Cell Testosterone Synthesis

Pathway: Cholesterol → Pregnenolone → 17-OH Pregnenolone → DHEA → Androstenedione → Testosterone

Testosterone Actions:

• Fetal development: Male genitalia differentiation, descent of testes
• Puberty: Secondary sexual characteristics (deep voice, facial hair, muscle mass)
• Anabolic: Protein synthesis, muscle growth
• Spermatogenesis: Required for maturation of spermatids
• Negative feedback: Inhibits LH (and GnRH pulse generator)

⚡ Exam tip: 5α-reductase converts testosterone → DHT (dihydrotestosterone); DHT is more potent for external genitalia development and prostate; Finasteride blocks 5α-reductase (used for BPH, male pattern baldness)

Female Reproductive System

Oogenesis (differs from spermatogenesis):

• Primordial germ cells → oogonia → primary oocytes
• Primary oocytes begin meiosis I → arrest at prophase I (months to years)
• Resume meiosis I before ovulation → secondary oocyte
• Arrest at metaphase II until fertilization
• If fertilized → completes meiosis II → ovum

Ovarian Follicle Development:

Stage	Key Events
Primordial follicle	Single layer of flat granulosa cells
Primary follicle	Cuboidal granulosa cells, zona pellucida begins forming
Secondary follicle	Multiple cell layers, antrum formation begins
Graafian follicle	Mature follicle, ready for ovulation
Corpus luteum	After ovulation; secretes progesterone, estrogen
Corpus albicans	Involuted corpus luteum (scar tissue)

Ovarian Steroid Production:

Cell Type	Hormone	Stimulus
Theca interna	Androgens (androstenedione)	LH
Granulosa cells	Convert androgens to estrogen	FSH (aromatase)
Corpus luteum	Progesterone + estrogen	LH (hCG if pregnancy)

⚡ Exam tip: PCOS (Polycystic Ovary Syndrome): ↑ androgens (from theca), ↓ estrogen, ↑ LH/FSH ratio, oligo/amenorrhea, hirsutism, obesity, insulin resistance; Associated with chronic anovulation

Menstrual Cycle (28-day ideal)

Phases:

Phase	Days	Key Events
Menstrual	1–4	Endometrial shedding (progesterone withdrawal)
Proliferative (Follicular)	5–14	Estrogen → endometrial regeneration, follicle growth
Ovulatory	Day 14	LH surge → ovulation (24–36 hr)
Secretory (Luteal)	15–28	Progesterone → endometrial maturation for implantation

Hormonal Regulation:

Hormone	Follicular Phase	Ovulation	Luteal Phase
FSH	Rising	Mid-cycle surge	↓ (inhibited by estrogen/inhibin)
LH	Low	Surge	↓ (inhibited by estrogen/inhibin)
Estrogen	↑ (E2 from growing follicle)	Peak triggers LH surge	↑ (from corpus luteum)
Progesterone	Low	Low	↑ (from corpus luteum)

⚡ Exam tip: LH surge (20–80 IU/L) triggers ovulation; Mid-luteal progesterone (>5 ng/mL) confirms ovulation; If no pregnancy, corpus luteum involutes → ↓ progesterone → menstruation

Fertilization and Early Embryology

Fertilization Process:

1. Sperm capacitation (in female reproductive tract, ~6–8 hr)
2. Acrosome reaction (requires zona pellucida proteins ZP3)
3. Sperm penetration of zona pellucida
4. Cortical reaction (prevents polyspermy)
5. Second meiotic division completion
6. Pronuclei fusion

Implantation:

• Day 5–6: Blastocyst hatches from zona pellucida
• Day 6–7: Apposition → adhesion → invasion
• hCG produced by syncytiotrophoblast from day 8
• hCG maintains corpus luteum → continued progesterone production

⚡ Exam tip: Twins: Dizygotic (fraternal, 2 eggs, 2 sperm, separate placentas possible) vs Monozygotic (identical, 1 egg, 1 sperm, splits after fertilization); Monochorionic twins always monozygotic

Placental Hormones

Hormone	Source	Function
hCG	Syncytiotrophoblast	Maintains corpus luteum (pregnancy test marker)
Progesterone	Syncytiotrophoblast	Maintains endometrium
Estrogen (E3)	Fetal liver + placenta	Breast development, uteroplacental blood flow
hPL	Syncytiotrophoblast	Insulin resistance, nutrient supply to fetus

⚡ Exam tip: hCG peaks at 10 weeks → then declines; Used to monitor pregnancy viability; Gestational trophoblastic disease (molar pregnancy) → very high hCG

Puberty

Male Puberty (9–14 years):

• First sign: Testicular enlargement (>4 mL)
• Pubarche: Pubic hair
• Adrenarche: Axillary hair, body odor
• Growth spurt: Peak at Tanner 3–4
• Spermarche: First ejaculation (~13–14 years)

Female Puberty (8–13 years):

• First sign: Breast development (thelarche)
• Pubarche: Pubic hair
• Growth spurt: Earlier than males (peak at Tanner 2–3)
• Menarche: First menstruation (~2.5 years after thelarche)

Hormonal Changes at Puberty:

• ↑ GnRH pulse frequency → ↑ FSH, LH → ↑ sex steroids
• Adrenarche: ↑ DHEA, androstenedione (independent of GnRH axis)

⚡ Exam tip: Precocious puberty (<8 yr in girls, <9 yr in boys): Central (GnRH-dependent) vs Peripheral (GnRH-independent); Delayed puberty: FSH, LH low = hypogonadotropic (Kallmann) vs high = hypergonadotropic (Turner)

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🔴 Extended — Deep Study (3mo+)

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Reproductive Physiology — Comprehensive NEET PG Notes

Detailed Male Reproductive Physiology

Semen Analysis (WHO criteria):

Parameter	Normal
Volume	≥1.5 mL
Sperm concentration	≥15 million/mL
Total sperm count	≥39 million/ejaculate
Motility	≥40% forward progressive
Morphology	≥4% normal forms
pH	≥7.2

Sperm Transport:

• Epididymis: 2–12 days (sperm gain motility and maturity)
• Vas deferens: Storage and transport
• *Ejaculatory duct: Contributes seminal fluid (fructose)
• Urethra: Final passage

Accessory Sex Gland Secretions:

Gland	Contribution
Seminal vesicles	60% of semen (fructose, prostaglandins, fibrinogen)
Prostate	25% of semen (citric acid, acid phosphatase, PSA)
Bulbourethral	Clear mucus (Cowper glands)

⚡ Exam tip: Fructose in semen = seminal vesicle function; Absence = obstructed ducts or congenital absence; PSA (prostate-specific antigen) = serine protease, liquefies semen; Elevated in prostate cancer

Hypothalamic-Pituitary-Gonadal Axis

GnRH Pulsatility:

Gender	Frequency	Effect
Follicular phase (female)	Every 60–90 min	↑ FSH > LH
Mid-cycle (female)	Continuous (no pulses)	LH surge
Luteal phase (female)	Every 2–3 hr	↓ LH
Male	Every 90–120 min	Steady LH and FSH

Testosterone Feedback:

• Negative feedback on hypothalamus and anterior pituitary
• ↓ GnRH pulse frequency → ↓ LH (more than FSH)
• Estrogen also provides negative feedback (from peripheral conversion of testosterone via aromatase)

Inhibin Feedback:

• Inhibin A (female): From dominant follicle/corpus luteum → ↓ FSH
• Inhibin B (male): From Sertoli cells → ↓ FSH (selective)

Detailed Female Reproductive Physiology

Ovulatory Cycle — Follicular Phase:

Early follicular (days 1–5):

• Low E2 and P4 → no negative feedback → FSH rises gradually
• FSH recruits follicles (normally one becomes dominant)

Mid-follicular (days 6–10):

• Dominant follicle produces E2 (via aromatase, stimulated by FSH)
• E2 → negative feedback → FSH declines (except in dominant follicle)
• E2 → positive feedback on pituitary (preparing for LH surge)

Late follicular (days 11–13):

• E2 peak (from dominant follicle) → positive feedback on pituitary
• LH surge begins (12–24 hr after E2 peak)
• Dominant follicle reaches Graafian stage (~20 mm)

Ovulation:

• LH surge (20–80 IU/L, 10× baseline) triggers:
  • Resumption of meiosis I in primary oocyte
  • Follicular rupture (via prostaglandins, proteases)
  • Luteinization of granulosa and theca cells
• Timing: ~36 hr after LH surge onset, 10–12 hr after peak

Luteal Phase:

• Corpus luteum forms → produces P4 and E2
• P4 prepares endometrium for implantation (decidualization)
• If no pregnancy → corpus luteum involutes (luteolysis) on day 22–23
• If pregnancy → hCG rescues corpus luteum (luteotrophic support)

⚡ Exam tip: Luteal phase defect = inadequate progesterone from corpus luteum → insufficient endometrial maturation → infertility, early miscarriage; Diagnosed by mid-luteal biopsy showing out-of-phase endometrium

Spermatogenesis — Detailed

Stages in Seminiferous Tubule (spermatogonia → sperm):

1. Mitotic division: A dark (stem) and A pale (committed) spermatogonia
2. S phase: B spermatogonia replicate DNA
3. Meiosis I: Primary spermatocytes → secondary spermatocytes
4. Meiosis II: Secondary spermatocytes → spermatids
5. Spermiogenesis: Spermatids transform into spermatozoa (flagellum, acrosome, cytoplasm shedding)

Sertoli Cell Functions (more detail):

• Physical support and nutrition
• Blood-testis barrier (tight junctions)
• Phagocytose residual bodies
• Secrete ABP (maintains high intratubular testosterone)
• Secrete inhibin B (regulates FSH)
• Secrete anti-Müllerian hormone (fetal testicular differentiation)

Detailed Menstrual Cycle — Endometrium

Endometrial Phases:

Phase	Days	Features
Menstrual	1–4	Coagulative necrosis, hemorrhage
Proliferative	5–14	Straight glands, mitotic activity (estrogen effect)
Secretory	15–28	Tortuous glands, glycogen-rich secretions (progesterone effect)

Endometrial Receptivity:

• Window of implantation: Days 20–24 (post-ovulation)
• Pinopodes: Uterine epithelial projections that disappear if no implantation

Contraception Methods

Method	Mechanism	Failure Rate (typical use)
Oral contraceptives	Suppress ovulation, thicken cervical mucus	5–9%
Copper IUD	Sperm toxicity, inflammatory reaction	0.8%
Hormonal IUD	Progestin → thick mucus, endometrial atrophy	0.2%
Condoms	Physical barrier	13%
Tubal ligation	Permanent sterilization	0.5%
Vasectomy	Blocks vas deferens	0.15%
Emergency contraception	LNG or ulipristal (Yuzpe)	Varies by timing

⚡ Exam tip: Progestin-only pill (mini-pill) — works primarily by thickening cervical mucus; Must be taken at same time daily (no missed pill allowed); Combined oral contraceptives (estrogen + progestin) — suppresses FSH/LH surge

Infertility Evaluation

Male Factor:

• Semen analysis
• Hormonal evaluation (testosterone, FSH, LH)
• Genetic testing (Karyotype, Y-chromosome microdeletions)
• Testicular biopsy

Female Factor:

• Ovulatory function (mid-luteal progesterone, BBT)
• Tubal patency (hysterosalpingogram)
• Uterine anatomy (ultrasound, hysteroscopy)
• Ovarian reserve (AFC, AMH, FSH on day 3)

Assisted Reproductive Technologies (ART):

Technique	Method
IVF-ET	External fertilization, embryo transfer
ICSI	Intracytoplasmic sperm injection
GIFT	Gamete intrafallopian transfer
ZIFT	Zygote intrafallopian transfer

⚡ Exam tip: PCOS infertility → first-line: letrozole (aromatase inhibitor) → ↓ estrogen → ↑ FSH; Clomiphene (SERM) second-line; Metformin adjunctive; Endometriosis → GnRH agonist, laparoscopic ablation

Sexual Differentiation

Chromosomal Sex: XX or XY (at fertilization)

Gonadal Differentiation (until week 7):

• Indifferent gonads develop from genital ridge
• SRY gene (Y chromosome) → testes-determining factor (TDF)
• Without SRY → ovaries develop (X chromosome dosage matters)

Phenotypic Differentiation:

Structure	Male (Anti-Müllerian + Androgens)	Female (Default)
Müllerian ducts	Regress (AMH from Sertoli cells)	Develop into uterus, fallopian tubes
Wolffian ducts	Develop (testosterone) → vas deferens	Regress
External genitalia	Virilize (DHT)	Default to female

⚡ Exam tip: 5α-reductase deficiency → XX babies appear female at birth but virilize at puberty (ambiguous → male); Because DHT needed for male external genitalia development; Androgen Insensitivity Syndrome (46,XY) → female external genitalia, testes, no uterus

Practice Questions for NEET PG

1. Describe the stages of spermatogenesis and the role of Sertoli cells.
2. Explain the hormonal changes during the menstrual cycle.
3. A couple is infertile. How do you evaluate male vs female factor?
4. What is the role of hCG in early pregnancy?
5. Compare the feedback regulation of testosterone in males with estrogen in females.
6. Describe the steps of fertilization.
7. A newborn has ambiguous genitalia. How do you determine genetic sex and guide further evaluation?

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