genital ridge

**Origin and formation** - The urogenital ridge arises from intermediate mesoderm. It has a lateral nephrogenic part (the mesonephros/kidney precursors) and a medial genital (gonadal) ridge. - The genital ridge forms at about week 5 from proliferating coelomic (mesothelial) epithelium and underlying mesenchyme, medial to the mesonephros. - Key transcription factors for formation include WT1, SF1 (NR5A1), LHX9 and GATA4. WT1 or SF1 mutations cause gonadal dysgenesis and associated defects. WT1 mutations are seen in WAGR syndrome, Denys-Drash syndrome and Frasier syndrome.

**Primordial germ cells (PGCs)** - PGCs arise from the epiblast and are found in the wall of the yolk sac near the allantois at about week 4. - They migrate along the dorsal mesentery of the hindgut and reach the genital ridge at weeks 5–6, where they induce proliferation of the coelomic epithelium. - Primary sex cords form around the PGCs. The gonad is bipotential and looks identical in XX and XY embryos until about week 7. - If PGCs fail to reach the ridge, the gonad does not develop properly and becomes a streak gonad.

**Sexual differentiation (from week 7)** - *XY:* - The SRY gene (Y chromosome, short arm) encodes TDF. It upregulates SOX9, which drives Sertoli cell differentiation. - Primary sex cords become seminiferous tubules and the rete testis. Sertoli cells secrete AMH (MIF), which causes regression of the paramesonephric (Müllerian) ducts. - Leydig cells secrete testosterone, which stimulates the mesonephric (Wolffian) ducts to form the epididymis, vas deferens and seminal vesicles. DHT, made by 5α-reductase, forms the external genitalia and prostate. - *XX:* - SRY is absent. WNT4, RSPO1 and FOXL2 promote ovarian development. - Primary sex cords degenerate. Secondary (cortical) sex cords form and surround the PGCs, which become oogonia and primordial follicles, with granulosa and theca cells. - There is no AMH, so the Müllerian ducts persist and form the fallopian tubes, uterus and upper vagina. Without testosterone, the Wolffian ducts regress.

**Clinical correlations** - *Gonadal dysgenesis:* - Turner syndrome (45,XO) causes streak ovaries. - Swyer syndrome (46,XY pure gonadal dysgenesis, often an SRY mutation) gives a female phenotype with a uterus and streak gonads. These gonads carry a high risk of gonadoblastoma/dysgerminoma, so gonadectomy is indicated. - *Disorders of sex development:* - Ovotesticular DSD (true hermaphroditism) has both ovarian and testicular tissue. - Androgen insensitivity syndrome is 46,XY with testes, a blind-ending vagina, no Müllerian structures and normal or high testosterone/LH. - 5α-reductase deficiency: virilization occurs at puberty. - Congenital adrenal hyperplasia (21-hydroxylase deficiency) causes a virilized 46,XX individual with normal ovaries and Müllerian structures. - *Gonadal descent:* - The gonads form in the upper lumbar region and then descend. - Testes descend via the gubernaculum through the inguinal canal into the scrotum (cryptorchidism if they fail). The processus vaginalis forms the tunica vaginalis. - Ovaries descend to the pelvis. The gubernaculum becomes the ovarian ligament and round ligament of the uterus. - Ovarian and testicular referred pain and lymphatic drainage follow the embryonic origin (para-aortic nodes).

**High-yield pearls** - Gonads, kidneys and the adrenal cortex all derive from mesoderm: the gonads and kidneys from intermediate mesoderm, the adrenal cortex from coelomic epithelium mesoderm. - The mesonephric (Wolffian) duct is male. The paramesonephric (Müllerian) duct is female. Mnemonic: Müllerian duct = Mother. - Müllerian ducts are the default female pathway. Female development does not need ovaries, but it needs absent SRY, and normal ovarian maintenance needs two X chromosomes. - The gonad is bipotential until SRY expression at about weeks 6–7.