Urogenital development

Three kidneys in sequence

All arise from intermediate mesoderm.

• Pronephros: week 4, cervical, never functions, disappears.
• Mesonephros: functions briefly; its duct, the mesonephric (Wolffian) duct, survives and matters for the male ducts and the ureter.
• Metanephros: the permanent kidney, from week 5, producing urine from about week 10–12. Fetal urine is the main source of amniotic fluid in the second half of pregnancy.

• The two parts induce each other: if the ureteric bud fails to reach the blastema, no kidney forms (renal agenesis) and the ureter is absent.
• Early splitting of the ureteric bud gives a bifid ureter; two separate buds give a duplex kidney with two ureters. The upper moiety ureter opens lower and more medially and may be ectopic or end in a ureterocele (Weigert–Meyer rule).
• The kidneys ascend from the pelvis to L1, rotating so the hilum faces medially, and pick up arteries from progressively higher vessels; leftover lower vessels persist as accessory renal arteries.
• WT1 (11p13) is needed for nephron and gonad formation. A deletion of 11p13 including WT1 and neighbouring PAX6 gives WAGR: Wilms tumour, aniridia (PAX6), genitourinary anomalies, intellectual disability.

Renal anomalies

Bladder and urethra

• The urorectal septum divides the cloaca into the anorectal canal behind and the urogenital sinus in front.
• The upper urogenital sinus forms the bladder, continuous above with the allantois. The allantois narrows into the urachus, which becomes the median umbilical ligament. A patent urachus leaks urine from the umbilicus; partial remnants form urachal cysts, sinuses or adenocarcinoma at the bladder dome.
• The trigone forms from the lower ends of the mesonephric ducts absorbed into the bladder wall (mesoderm, later covered by endoderm).
• Bladder exstrophy: failure of the infraumbilical body wall; the open bladder mucosa lies on the lower abdomen and is constantly wet with urine, with epispadias and separated pubic bones.

Gonads and sex determination

• The indifferent gonad forms on the genital ridge; primordial germ cells migrate from the yolk sac wall. Both duct systems exist until week 7.

• Without SRY the gonad becomes an ovary. Without AMH the paramesonephric (Müllerian) ducts form the uterine tubes, uterus, cervix and upper vagina; their lower fused ends meet the urogenital sinus at the Müllerian tubercle (male counterpart: seminal colliculus). Without testosterone the mesonephric ducts regress, leaving remnants (Gartner duct cyst, epoophoron). In the male the paramesonephric remnants are the appendix testis and prostatic utricle.
• Uterine anomalies come from incomplete fusion of the paramesonephric ducts: bicornuate uterus (partial fusion), uterus didelphys (no fusion), septate uterus (failed resorption of the septum). Because the ducts develop beside the mesonephric system, they are often associated with renal anomalies.
• Müllerian agenesis (MRKH): 46,XX, normal ovaries and breasts (oestrogen is normal), primary amenorrhoea with absent uterus and upper vagina; a paramesonephric duct failure.

External genitalia and homologues

• Hypospadias: failure of the urethral folds to fuse, so the meatus opens on the ventral penis; commonest penile anomaly. Epispadias: dorsal opening, with exstrophy.

Descent of the testis

• The testis, guided by the gubernaculum, lies at the deep inguinal ring by about 3 months, passes through the inguinal canal at about 7 months (weeks 26–28) and reaches the scrotum around birth. It follows an outpouching of peritoneum, the processus vaginalis, which should then close, leaving the tunica vaginalis.
• Patent processus vaginalis: a narrow patency lets fluid in, giving a communicating hydrocele that transilluminates and is smaller in the morning; a wider one allows an indirect inguinal hernia. Most infant hydroceles close by 1–2 years; repair is through an inguinal approach.
• Undescended testis (cryptorchidism): the higher temperature damages germ cells, so the risks are infertility and germ cell tumour (seminoma), plus torsion and hernia. Orchidopexy at 6–18 months protects fertility and lowers (but does not remove) cancer risk, and places the testis where it can be examined.

Disorders of sex development

Remember SRY makes the testis, AMH removes the female ducts, testosterone keeps the male ducts, DHT shapes the outside.

Exam trap The ureteric bud makes the collecting system; the blastema makes the nephrons.

Exam trap Bicornuate uterus and MRKH are paramesonephric faults, often with renal anomalies.

How FCPS asks about this

• Mesonephric duct derivative in the male: vas deferens (also epididymis, seminal vesicle, ejaculatory duct, ureteric bud and trigone).
• Horseshoe kidney: ascent blocked by the inferior mesenteric artery; Turner syndrome.
• Duplex kidney with two ureters: early division or duplication of the ureteric bud.
• Ambiguous genitalia with salt wasting: 21-hydroxylase deficiency; raised 17-hydroxyprogesterone.
• 46,XY ambiguous at birth, virilises at puberty: 5α-reductase deficiency; lack of DHT.
• Male fetus with bilateral hydronephrosis and keyhole bladder: posterior urethral valves; confirm with MCUG.
• Transilluminating hydrocele in an infant: patent processus vaginalis; orchidopexy for undescended testis at 6–18 months.