labioscrotal folds

**Embryology** - External genitalia are indifferent (bipotential) until about week 9 and are distinguishable by about week 12. - Bipotential structures: genital tubercle, urogenital folds, labioscrotal folds (also called genital swellings). - The labioscrotal folds lie lateral to the urogenital folds.

**Fate by sex** - Male: the folds fuse in the midline to form the scrotum. Fusion forms the scrotal raphe. Development depends on DHT, made from testosterone by 5-alpha-reductase type 2. - Female: without DHT, the folds stay mostly unfused and form the labia majora. The anterior and posterior labial commissures mark where they meet.

**Homologous structures (high-yield)** - Genital tubercle: glans penis (male); glans clitoris (female). - Urogenital folds: ventral shaft of the penis, including the spongy (penile) urethra (male); labia minora (female). - Labioscrotal folds: scrotum (male); labia majora (female).

**Hormonal control** - Testosterone, made by Leydig cells (stimulated by hCG, then LH), drives the Wolffian duct derivatives (epididymis, vas deferens, seminal vesicles). - DHT drives the external genitalia: penis, scrotum, and prostate. - Mnemonic: "T for internal, DHT for external."

**Clinical correlations** - 5-alpha-reductase type 2 deficiency (46,XY DSD): - Normal testes and normal Wolffian ducts. Müllerian structures are absent because AMH is intact. - External genitalia are ambiguous or appear female at birth, with a poorly fused scrotum. - At puberty, testosterone rises and virilization occurs, with a "penis at 12" presentation. - Testosterone is normal or high, DHT is low, and the T:DHT ratio is elevated. - Androgen insensitivity syndrome (46,XY): - Defective androgen receptor. Testosterone and LH are high. - Female external genitalia with a blind-ending vagina, and no uterus because AMH is intact. - Testes are intra-abdominal or inguinal. Sparse or absent pubic hair. - Congenital adrenal hyperplasia, 21-hydroxylase deficiency (46,XX): - Excess androgens virilize the female external genitalia. - Findings include clitoromegaly and partial fusion of the labioscrotal folds, which look rugated and scrotum-like. - The internal organs (ovaries, uterus) are normal. - Associated with salt wasting, hypotension, hyperkalemia, and high 17-hydroxyprogesterone. - Maternal androgen exposure or placental aromatase deficiency can also virilize a 46,XX fetus. - Hypospadias: failed fusion of the urogenital folds (not the labioscrotal folds). It can accompany a bifid scrotum when severe.

**Related anatomy** - Lymphatic drainage of the scrotum and labia majora goes to the superficial inguinal nodes. - Sensory innervation: the anterior scrotum and labia majora via the ilioinguinal nerve and the genital branch of the genitofemoral nerve. The posterior portion is supplied by the pudendal nerve (perineal branches) and the posterior femoral cutaneous nerve. - The gubernaculum ends in the labioscrotal folds. In males it guides testicular descent into the scrotum. In females it becomes the round ligament of the uterus, which ends in the labia majora.

**Board pearl** Ambiguous genitalia in a 46,XX infant with salt wasting means CAH (21-hydroxylase deficiency). A 46,XY patient with a female phenotype, a blind vagina, and no uterus means AIS. A 46,XY patient with ambiguous genitalia at birth who virilizes at puberty means 5-alpha-reductase deficiency.