Development and congenital anomalies of the urogenital system

Kidney

The pronephros is a transitory structure at the level of the developing heart. A primary excretory duct can be seen in stage 11 embryos (29–30 days post fertilization). The mesonephros extends from somite 8–20 and forms nephrons that connect to the excretory duct (now termed mesonephric duct) sequentially in a rostrocaudal manner. The organ produces amniotic fluid by stage 17 (39–41 days post fertilization). The cranial end of the mesonephros atrophies; in the male, the nephrons in the mid portion become the efferent ductules of the testis (see later).

The mesonephric duct connects with the urogenital sinus, an endodermal diverticulum derived from the allantois that is confluent with the enteric hindgut at the cloaca. The permanent kidneys develop from an outgrowth of the lowest part of the mesonephric duct, the ureteric bud (stage 16, 37–38 days post fertilization). This interacts with surrounding metanephric mesenchyme, which forms metanephric nephrons; angiogenic mesenchyme migrates into the developing metanephros later to form the glomeruli and vasa recta, adjacent to the loops of Henle. Metanephric nephrons start forming from stage 21 (50–52 days post fertilization) and contribute to amniotic fluid production from week nine. The metanephric kidneys are initially sacral but with differential growth of the embryo they ascend cephalically to the level of the second lumbar vertebra, gaining sequential arterial blood supplies during their ascent; the definitive renal artery is recognizable by the beginning of the third month.

Bladder

The primitive hindgut, the cloaca, is formed by an enteric portion and the allantois, a blind-ending diverticulum that projects into the connective stalk between the umbilical blood vessels. The cloaca will form the anorectal canal, urethra and bladder, and the vagina in females ; perturbations of its development may give rise to complex cloacal malformations.

The urinary and enteric portions of the cloaca become separated by the growth of the urorectal septum, endodermal epithelium and underlying mesenchyme ( Fig. 75.1 ). This creates the anorectum dorsally and the urogenital sinus ventrally. The superior extension of the urogenital sinus, the allantois, narrows, forming the urachus, which ultimately becomes the median umbilical ligament. The ureters extend from the ureteric bud and open separately into the dorsal wall of the urogenital sinus, lateral to the openings of the paramesonephric and mesonephric ducts. These orifices become further separated as the bladder enlarges, so that the ureters open laterally into the superior part of the trigone, whereas (in the male) the mesonephric ducts move caudally to open into the future prostatic urethra ( Fig. 75.2 ). The internal, endodermal, epithelium of the bladder differentiates into transitional epithelium. The outer lamina propria, muscularis and adventitia derive from the surrounding splanchnopleuric mesenchyme. In the neonate, the superior half of the bladder is above the pubic symphysis and does not gain its adult position until 6 years.

Reproductive ducts

The mesonephric (Wolffian) duct develops as the excretory duct of each mesonephros. The mesonephric nephrons become the efferent ductules of the testis, and the mesonephric duct forms the epididymis, vas (ductus) deferens, seminal vesicles and ejaculatory ducts ( Fig. 75.3 ). Paramesonephric (Müllerian) ducts, first seen from 35 days post fertilization, invaginate from the coelomic epithelium into the dorsal wall of the peritoneal cavity bilaterally and extend caudally, lateral to each mesonephric duct. At the caudal end of the mesonephros each duct turns medially, crossing ventral to the mesonephric duct, then continues growing caudally in close contact, and ultimately fusing, with the contralateral duct. The paramesonephric ducts become the uterine tubes, the body of the uterus and uterine cervix (see Fig. 75.3 ). The two ducts enter the dorsal wall of the urogenital sinus, producing an elevation, the Müllerian or sinus tubercle, which induces vaginal development. Failure of fusion of the two paramesonephric ducts can result in a range of uterovaginal anomalies, including uterus didelphys and double vagina.

Gonadal tissue develops on the surface of each mesonephros, within a genital ridge of proliferating coelomic epithelium interacting with the underlying mesonephric mesenchyme. Primordial germ cells migrate from an early extraembryonic site close to the cloaca and enter the genital ridge from stage 15 (35–36 days post fertilization). They become incorporated into the proliferating coelomic epithelium, close to the mesonephric nephrons.

Male

Possession of a Y chromosome and its sex-determining region ( SRY ) gene initiates a male reproductive programme. The coelomic epithelial cells become Sertoli cells, which surround the primordial germ cells. Sertoli cells secrete anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS), which promotes mesonephric duct growth and paramesonephric duct apoptosis. Mesonephric mesenchymal cells become the cells of Leydig, which secrete testosterone.

The testes move relatively lower in the body as the remaining mesonephros involutes. A condensation of mesenchyme from the lower end of the gonad, the gubernaculum, connects the testis to the anterior abdominal wall at the site of the future inguinal canal. The gubernaculum enlarges and a crescentic column of peritoneum, the processus vaginalis, extends into it ( Fig. 75.4 ). The testis is in apposition with the deep inguinal ring during the fourth to sixth months. Testis descent into the scrotum occurs relatively rapidly during the seventh month, the left testis descending ahead of the right. The layers of processus vaginalis involute proximally, remaining around the vas deferens and the testis as the tunica vaginalis. Layers of the anterior abdominal wall form the layers of the spermatic cord as the testis passes along the inguinal canal and into the scrotum.

External genital development

External genitalia are initially similar in both sexes and early external determination of sex is difficult. A midline genital tubercle appears at the cranial end of the urogenital membrane with two lateral ridges, the genital (urethral) folds. Elongation of these protuberances produces a primitive phallus. Lateral folds (scrotal or labial) develop later ( Fig. 75.5 ). When the urogenital membrane breaks down, the internal, endodermal, portion of the urogenital sinus is open to the amniotic cavity.

In females, the genital folds remain separated as labia minora. In rare disorders of sex development, fetuses that are XY but lack testosterone receptors become phenotypically female. In males, the genital folds fuse with each other to form the bulb of the urethra and the greater part of the spongiose urethra. The penile urethra is completed by an ingrowth of ectodermal epithelium from the distal tip (glans) of the penis. In males, failure of fusion of the genital folds, or of the canalization of the ectodermal and endodermal parts of the urethra, results in hypospadias.

An ectodermal fold, containing mesenchyme, grows over the glans of the penis, forming the prepuce. Abnormal urethral development impairs formation of a ventral prepuce. The preputial sac may not be complete until 6–12 months or more after birth; thus at birth it is usually not possible to retract the foreskin. This is because the opening to the prepuce is too narrow and inelastic, and also because the inner prepuce is adherent to the glans. Over time, the preputial opening becomes wider and more elastic, and the preputial adhesions separate. Although many boys will be able to retract their foreskin by the time they reach school, it is very common for the process not to be complete until a boy reaches puberty.