Reproductive Histology
A board-focused tour of reproductive histology anchored on gonadotropin targets and secretory products: Sertoli/granulosa (FSH) versus Leydig/theca (LH), the ovarian two-cell model, and classic buzzwords — Reinke crystals, Call–Exner bodies, stereocilia, and corpora amylacea — plus the clinical vignettes that test them.
The one blueprint behind both gonads
On Step 1, reproductive histology rewards two questions: which cell responds to which gonadotropin, and which cell secretes what. The gonads share one blueprint. In the testis, seminiferous tubules contain Sertoli cells (support, barrier) plus maturing germ cells, while Leydig cells occupy the interstitium. In the ovary, granulosa cells line each follicle and theca cells wrap around it. The pairing is exact: Sertoli ≈ granulosa (both FSH-driven; both aromatize androgen to estrogen and make inhibin) and Leydig ≈ theca (both LH-driven androgen factories). Learn that homology and most 'identify the cell,' feedback, and gonadal-tumor vignettes resolve fast.
- Sertoli cells line the seminiferous tubules; FSH-responsive; form the blood–testis barrier via tight junctions (isolates haploid germ cells from the immune system)
- Secrete inhibin B (negative feedback on FSH), androgen-binding protein (ABP) (keeps intratubular testosterone high), and AMH/MIS (fetal Müllerian duct regression)
- Contain aromatase → convert testosterone to estrogen; temperature-sensitive (cryptorchidism, varicocele → impaired spermatogenesis, ↓ inhibin B, ↑ FSH)
- Leydig cells sit in the interstitium; LH-responsive; secrete testosterone; contain rod-shaped Reinke crystals
- Germ line: spermatogonium → 1° spermatocyte → 2° spermatocyte → spermatid → spermatozoon (spermiogenesis = spermatid → mature sperm, occurring adluminal to the barrier)
- Two-cell, two-gonadotropin model: LH → theca interna makes androstenedione (cholesterol → androgen via desmolase); androgen diffuses to granulosa cells, where FSH → aromatase yields estradiol
- Granulosa cells can't make androgen de novo (lack 17α-hydroxylase/17,20-lyase = CYP17) → they depend on theca-derived androgen; they also secrete inhibin B
- Follicle stages: primordial → primary → secondary (preantral) → antral/tertiary (antrum forms) → Graafian/preovulatory
- Corpus luteum (granulosa-lutein + theca-lutein) secretes progesterone (and estrogen) to sustain the secretory endometrium; without hCG rescue it involutes to a corpus albicans
- Call–Exner bodies (rosettes around pink material) → granulosa cell tumor: estrogen/inhibin → precocious puberty (juvenile) or postmenopausal bleeding + endometrial hyperplasia (adult)
Male–female histologic homologs
| Feature | Sertoli (♂) ≈ Granulosa (♀) | Leydig (♂) ≈ Theca (♀) |
|---|---|---|
| Gonadotropin | FSH | LH |
| Location | Lines tubule / follicle | Interstitium / theca layer |
| Secretes | Inhibin B; aromatase→estrogen; AMH; ABP (Sertoli-only) | Androgens (testosterone / androstenedione) |
| Buzzword | Blood–testis barrier; Call–Exner (granulosa tumor) | Reinke crystals (Leydig tumor) |
Vignette: A 40-year-old man reports gynecomastia, low libido, and a painless testicular nodule; scrotal ultrasound shows a solid intratesticular mass.
Next step: Radical (inguinal) orchiectomy — the standard approach for any solid testicular mass; avoid trans-scrotal biopsy/approach (tumor seeding, altered lymphatic drainage). The resected specimen shows sheets of polygonal cells with abundant eosinophilic cytoplasm and rod-shaped cytoplasmic crystals.
Diagnosis: Leydig cell tumor — the crystals are Reinke crystals. These sex cord–stromal tumors secrete androgens and/or estrogens → gynecomastia and low libido in adults, precocious puberty in boys. Most are benign. Ovarian analog: granulosa cell tumor (Call–Exner bodies, estrogen excess).
Vignette: An infertile 38-year-old man had a vasectomy 6 years ago, later reversed. Semen analysis shows sperm agglutination; anti-sperm antibodies are positive.
Concept: The blood–testis barrier (Sertoli tight junctions) normally sequesters developing sperm, which express neoantigens that first appear at puberty — after central immune tolerance was already established. Trauma, vasectomy, infection, or torsion breach the barrier and expose sperm antigens → anti-sperm antibodies and autoimmune orchitis, a cause of infertility.
Board hook: the 'immunologically privileged' testis; the barrier sits between adjacent Sertoli cells, dividing the tubule into a basal compartment (spermatogonia) and an adluminal compartment (meiotic and haploid cells).
- Epididymis / vas deferens — pseudostratified columnar with long, nonmotile stereocilia (tall microvilli); the vas has a thick 3-layer smooth-muscle wall
- Prostate — glands with corpora amylacea (lamellated eosinophilic concretions that increase with age)
- Cervix transformation zone — the squamocolumnar junction; site of squamous metaplasia and HPV dysplasia → most cervical cancers arise here
- Endometrium — proliferative phase (estrogen: straight glands, mitoses) vs secretory phase (progesterone: coiled 'sawtooth' glands, subnuclear vacuoles → luminal secretions)
- Vagina — nonkeratinized stratified squamous, glycogen-rich under estrogen (feeds lactobacilli → acidic pH)
- LH → Leydig (both start with L); Leydig testosterone = the libido/virilization hormone
- FSH → Sertoli (and granulosa) — Sertoli = the sustentacular support cell; FSH also drives granulosa aromatase
- Two-cell model: theca → androgen, granulosa → estrogen (via aromatase); granulosa can't make androgen alone
- Reinke crystals ≈ Leydig tumor; Call–Exner bodies ≈ granulosa cell tumor
- Core homology: Sertoli : Leydig :: Granulosa : Theca
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