Wolffian duct

**Memory aid:** "SEED" = Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens (vas deferens). Wolffian = "Wolf-man" = male. Also gives efferent ductules and appendix of the epididymis. The ureteric bud arises from the Wolffian duct.

**Embryology:** - Mesonephric (Wolffian) ducts form in both sexes from intermediate mesoderm and drain the mesonephros into the cloaca/urogenital sinus. - The paramesonephric (Müllerian) ducts form alongside them in both sexes. - Sex determination: SRY (Y chromosome) → SOX9 → Sertoli cells and Leydig cells. - Leydig cells secrete testosterone (stimulated by hCG early on). Testosterone acts locally and paracrine/ipsilaterally on the Wolffian duct and maintains it. - Sertoli cells secrete anti-Müllerian hormone (AMH/MIS), which causes Müllerian duct regression. - Dihydrotestosterone (DHT, made from testosterone by 5-alpha-reductase) is required for external genitalia (penis, scrotum, prostate), NOT for Wolffian duct derivatives. - Female (no SRY, no testosterone): Wolffian ducts regress. Müllerian ducts persist → fallopian tubes, uterus, cervix, upper 1/3 of vagina.

**Derivatives:** - Male: efferent ductules, epididymis, ductus (vas) deferens, ejaculatory duct, seminal vesicles, appendix of epididymis. Ureteric bud (→ ureter, renal pelvis, calyces, collecting ducts) also arises from the mesonephric duct. - Female vestigial remnants: Gartner duct cyst (vaginal/anterolateral wall cysts), epoophoron, paroophoron. - Note: the prostate arises from the urogenital sinus (endoderm), not the Wolffian duct (DHT-dependent).

**Clinical correlations:** - Androgen insensitivity syndrome (46,XY; defective androgen receptor): testes present, AMH is made so there is no uterus/tubes, but there is no response to testosterone/DHT → Wolffian structures absent/underdeveloped; female external genitalia, blind-ending vagina, undescended testes, scant pubic/axillary hair, elevated testosterone and LH. - 5-alpha-reductase deficiency (46,XY): normal testosterone → Wolffian derivatives (epididymis, vas, seminal vesicles) develop normally, but ambiguous/female-appearing external genitalia at birth with virilization at puberty (rise in testosterone). - Congenital bilateral absence of the vas deferens (CBAVD): Wolffian duct–derived defect, associated with CFTR mutations (cystic fibrosis) → obstructive azoospermia. Often with absent/atrophic seminal vesicles. - Unilateral renal agenesis with ipsilateral absence of vas deferens/seminal vesicle: failure of mesonephric duct/ureteric bud development. - Ectopic ureter: abnormal ureteric bud origin from the Wolffian duct; may insert into the vas/seminal vesicle (male) or the vagina/urethra (female) → incontinence in females. - Gartner duct cysts: remnant in females, anterolateral vaginal wall. - Persistent Müllerian duct syndrome: AMH or AMH receptor defect → uterus/tubes present in a 46,XY male with normal Wolffian derivatives; often with cryptorchidism. - Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser): 46,XX, normal ovaries, primary amenorrhea, absent uterus/upper vagina; associated with renal anomalies. - Congenital adrenal hyperplasia (21-hydroxylase deficiency) in 46,XX: excess androgens can partially stimulate Wolffian structures and virilize external genitalia, but internal female structures persist (ovaries do not make AMH).

**High-yield pearls:** - Wolffian = testosterone (internal male genitalia, ipsilateral). Müllerian = absent AMH. - External male genitalia and prostate = DHT. - In a 46,XY individual with testes and no testosterone effect, both Müllerian regression (AMH) and Wolffian absence can coexist (AIS).