Urogenital System Development Overview

Provided by Matt Kaufman, University of Edinburgh. Other Contributors are Jamie Davies, Peter Koopman, Melissa Little, Cathy Mendelsohn, Gen Yamada, Andrew McMahon
2010 (GUDMAP)

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The developing urinary and reproductive systems tend to be viewed as a single entity because both arise mainly from a common embryological origin, the intermediate mesoderm. This differentiates to form the nephrogenic cord, a column of condensed mesodermal tissue that extends caudally from the future cervical (neck) region. The intermediate mesoderm extends towards, but does not reach, the urogenital sinus, which is initially continuous with the most caudal (and ventral) component of the embryonic hindgut, but which will later become separated from it (see below).

The initial renal anlage that develops from the most rostral part of each nephrogenic cord is termed the pronephros and is not believed to function in any mammal. It consists of a small number of pronephric (or nephrotomal) vesicles that drain into the pronephric portion of the nephric duct. Despite the later degeneration of the pronephros, the pronephric duct is retained and extends caudally to be used by the mesonephros (also termed the “Wolffian” body), and is only then termed the mesonephric portion of the nephric duct.

The mesonephros develops primitive glomeruli, 4-6 of which drain through a mesonephric tubule to the mesonephric portion of the nephric duct, and this temporary kidney is therefore believed to be functional, producing some amniotic fluid. Each mesonephros also produces about 35 more caudal tubules, which do not connect to the mesonephric duct in mice.

In both sexes, a gonadal ridge forms along most of the medial aspect of the mesonephros. Primordial germ cells, arising from the yolk sac, then invade the gonadal ridge by way of the wall of the hindgut and its dorsal mesentery. In male embryos, the primary sex cords differentiate from the surface tissue of the gonads, invade the subjacent tissue and give rise to the seminiferous cords within which the germ cells are located. The “drainage” system of each future testis (efferent ducts, epididymis, ductus (or vas) deferens, seminal vesicles and ejaculatory duct) is derived from the mesonephric portion of the nephric duct and mesonephric tubules. The prostate gland develops from the urogenital sinus. In female embryos, the primary sex cords regress, and are replaced by the ovigerous cords. Ovigerous cords represent strings of germ cells, in which later the intercellular bridges between germ cells breaks down and single oocytes become closely surrounded by a somatic epithelial monolayer of pre-granulosa cells. The oviducts, uterine horns and the upper one-third of the vagina are derived from the paramesonephric (or Müllerian) ducts which arise from the surface of each mesonephros. The more caudal part of the vagina is believed to form from the urogenital sinus.

The mesonephric duct continues to extend caudally until it makes contact with the urogenital sinus in the region that eventually corresponds with the supero-lateral part of the trigone of the future bladder. Its caudal part then produces a cranio-laterally directed diverticulum, termed the ureteric bud, which invades the most caudal part of the nephrogenic cord tissue and begins to bifurcate repeatedly therein to form the primitive collecting duct system (ureteric tree) of the metanephros (permanent kidney). The mesenchyme invaded by the bud forms excretory nephrons that connect to the collecting duct system and drain through it.

**The developing urogenital system.**
From left to right, 3-dimensional schematic diagrams show the urogenital system at TS17 (10.5 dpc), TS19 (11.5 dpc), TS21 (13 dpc) and TS23 (15 dpc). Ventral views of male (top row) and female (bottom row) systems are shown. The anatomy of the gonads (blue) is identical at TS17 and 19, becoming an obvious testis and ovary, seen at TS21 and TS23. Primordial germ cells, in the early gonad, and germ cells (white spheres) are part of the ovary and testis. AT TS21, male germ cells are located within the primary sex cords, giving the testes their striped appearance. A mesonephros lies adjacent to each gonad and can be seen at all four stages, in both males and females. Within the mesonephroi (purple-grey) are the nephric ducts and their derivatives (orange), the paramesonephric ducts (blue) and the mesonephric tubules (grey). The urinary system can be divided into the upper and lower systems. The lower urinary system is primarily derived from the cloaca (dark purple at TS17). The cloaca gives rise to the urogenital sinus (dark purple at TS19), which gives rise to the bladder and pelvic urethra (dark purple at TS21 and 23). The phallic urethra and external genitalia are not shown. The upper urinary system is comprised of the metanephroi or kidneys. Each metanephros (kidney) develops from the metanephric mesenchyme (purple at T17), located adjacent to the posterior end of the nephric duct. Here, the ureteric bud grows out from this portion of the nephric duct, just after TS17, and T-shaped ureteric buds can be seen within the metanephric mesenchyme at TS19. The ureteric bud continues to branch developing into the ureteric tree seen at TS21 and TS23. Only the ureteric tips are shown on the surface of the kidneys at these later stages. The metanephric mesenchyme condenses around the ureteric tips, forming the cap mesenchyme (darker purple in TS21 and TS23 kidneys). Cells of the cap mesenchyme give rise to the nephrons of the kidney (not shown in the diagrams). The ureters, part of the lower urinary system, develop from the stalks of the ureteric buds. Remodelling of the posterior nephric duct (called the common nephric duct) occurs between TS19 and TS21, eventually resulting in a direction connection between the ureters and the bladder and completing the connection between the upper and lower urinary systems.

**The developing urogenital system – dorsal views.**
From left to right, 3-dimensional schematic diagrams show the male urogenital system at TS17 (10.5 dpc), TS19 (11.5 dpc), TS21 (13 dpc) and TS23 (15 dpc). Dorsal views of the urogenital system, show the kidneys and the dorsal sides of the mesonephroi. The mesonephric tubules are more visible from the dorsal side. The lower urinary system, shown in dark purple, shows the dorsal side of the cloaca (at TS17), urogenital sinus (at TS19) and the dorsal side of the pelvic urethra (TS21 and TS23). The bladder is not seen in dorsal views of the urogenital system. The pelvic ganglia (white spheres) can be seen on this side of the anterior pelvic urethra. The phallic urethra and external genitalia are not shown.

Development of the Murine Urinary System >>