Genitourinary system

Intermediate mesoderm gives rise to the kidneys, ureters, gonads and genital ducts. It forms the urogenital ridge along with the coelomic mesothelial cells. It differentiates into the lateral nephrogenic cord and medial genital ridge.

The urinary system develops craniocaudally in three evolutionary distinct stages namely the pronephros, mesonephros and metanephros. The adult kidney develops from the metanephros. The adult kidney develops in the pelvic region and it ascends to its normal position in the abdomen by the end of the 9th week of development. Ascent is not an active process rather it results from rapid longitudinal growth of the lumbosacral vertebrae and growth of abdominal and thoracic viscera. At the same time, the renal hilum changes position from ventral to medial by undergoing a 90 degree rotation. The metanephros shows two distinct features - the ureteric bud that is derived from the mesonephric duct or Wolffian duct and the metanephric blastema that develops from the intermediate mesoderm. The ureteric bud develops into the ureter , pelvicalyceal system and collecting ducts. While the metanephric blastema develops into the nephrons consisting of podocytes, epithelium of the Bowman’s capsule, PCT, DCT and the loop of Henle. Both systems induce the development of each other by a mechanism involving retinoic acid. Signalling via the NOTCH pathway is crucial for development of the proximal renal structures like glomeruli and PCT. The glomerular capillaries are derived from mesoderm.

The allantois extends from the yolk sac and becomes a part of the umbilical cord. It gives rise to the urachus. The urachus connects to the cranial end of the urogenital sinus (endoderm) and gives rise to the urinary bladder and urethra. The urinary bladder and urethra develop from endoderm except for the trigone of the bladder which is mesodermal originating from the mesonephric ducts and smooth muscle which originates from the splanchnic mesoderm.

Adrenal cortex is derived from the intermediate mesoderm of the mesonephric tubules. Adrenal medulla develops from ectoderm of the neural crest.

Polycystic kidneys

Aberrant differentiation, induction and proliferation of the developing renal tubular system leads to formation of cysts. Multiple cysts are seen in the kidneys in polycystic disease. The cysts may become symptomatic later in life but they start forming during the intrauterine period. Mutations in the gene coding for a transmembrane protein called fibrocystin or polyductin has been implicated as the root cause. Fibrocystin/polyductin or polycystin PC1 and PC2, is thought to mediate terminal differentiation of the renal collecting ducts and intrahepatic biliary ducts. Fibrocystin is normally located at the basolateral plasma membrane, primary cilia and the centrosome in renal epithelial cells. ADPKD kidneys and ADPKD polycystic livers, showed an approximately 2-fold increase in PC1 mRNA compared to normal kidneys and livers.

Renal agenesis or hypoplasia

Absent or underdeveloped kidneys will present as oligohydramnios and Potter syndrome. Low amniotic fluid leads to increased pressure on the developing organs causing Potter syndrome. It manifests as hypoplasia of the lungs and gut, sloped forehead, shortened fingers and “parrot beak” appearance of nose.

Pelvic kidney

This occurs due to arrested ascent of the kidney which stays in the pelvic cavity rather than normal location in the posterior upper abdomen.

Horseshoe kidney

In this condition, both kidneys fuse together forming a “U” (horseshoe) shaped organ. During development, the horseshoe kidney gets trapped in the lower abdomen by the IMA that prevents further ascent. It has been associated with alcohol consumption in pregnancy, thalidomide and maternal diabetes. It may be asymptomatic or present with UTIs, abdominal pain and mass. It is often accompanied with anomalies of renal artery and vein. There is a higher risk of Wilms tumor, transitional cell carcinoma and carcinoid tumors in a horseshoe kidney.

PUJ obstruction

Incomplete recanalisation of the pelviureteric junction during intrauterine development leads to obstruction. It is the most common cause of pediatric hydronephrosis. Sometimes the obstruction may be due to extrinsic causes like aberrant vessels or fibrotic bands crossing the PUJ.

Renal Coloboma Syndrome

Also known as papillorenal syndrome, it is characterised by hypoplastic kidneys and optic nerve coloboma. It may be associated with vesicoureteral reflux or VUR, renal cysts and . Mutations in PAX2 gene which codes for a transcription factor are seen. It is inherited as an autosomal dominant condition.

Disorders of the urachus

During the development of an embryo, the urachus extends from the bladder to the umbilicus. It normally is sealed off and becomes the median umbilical ligament. The entire urachus may remain patent and present postnatally as discharge of urine from the umbilicus. Sometimes the ventral end of the urachus remains patent forming a urachal sinus. A sinus may get infected causing local pain and discharge. When only the distal end of the urachus remains patent it forms a diverticulum of the bladder. It may cause UTIs. The urachal remnants may form a cyst.

Reproductive System

The gonads arise from the intermediate mesoderm of the urogenital ridge. The gonads are indifferent till 7 weeks of intrauterine life. Sex is determined at fertilisation but differentiation of a XY embryo into a phenotypically male fetus is determined by SRY (sex determining region Y) on the Y chromosome. SRY promotes the development of testes, Sertoli and Leydig cells. Testosterone secreted by the Leydig cells supports the growth of the mesonephric ducts. DHT or dihydrotestosterone supports the growth of the prostate gland, penis and scrotum. Sertoli cells also produce anti Mullerian hormone or AMH or MIS which induces regression of the paramesonephric or Mullerian ducts.

In males the mesonephric or Wolffian ducts become efferent ducts including the epididymis, rete testis, vas deferens and seminal vesicles. In females, it remains as epoophoron and paroophoron and Gartner’s ducts. The mullerian or paramesonephric ducts in females become the fallopian tubes, uterus, cervix and the upper ⅓ of the vagina. In males, remnants are seen in the prostatic utricle.

The prostate gland starts to develop laterally as epithelial buds from the urogenital sinus wall. These buds branch into solid cords which canalize and form the ducts and acini. The surrounding urogenital sinus mesenchyme forms the interfascicular fibroblasts and the smooth muscle of the prostate. Bulbourethral glands, vestibule, urethra and lower ⅔ of the vagina develop from the urogenital sinus (endoderm). The Wolffian ducts regress in females.

Proliferation of ectoderm and mesoderm form the genital tubercles, folds and swellings. Genital tubercle gives rise to the body and glans of penis, corpora cavernosa and corpus spongiosum in males and clitoris in females. Genital folds become the ventral aspect of penis and penile raphe in males and labia minora in females. Genital swellings become scrotum and scrotal raphe in males and labia majora and mons pubis in females.