Development of Urinary System

Most of the urinary system develops from the intermediate mesoderm and the caudal hindgut during embryogenesis in the embryonic period. Derivatives of the intermediate mesoderm include the nephrogenic cord and the ureteric bud, which give rise to the kidneys and ureters, respectively. The urinary bladder and proximal urethra develop chiefly from the ventral portion of the cloaca.

Kidney and Ureter

The kidney develops in the 2nd month from the metanephros, the caudal portion of the nephrogenic cord, which is derived from intermediate mesoderm. The ureter and the intrarenal collecting system develop from the ureteric bud (metanephric diverticulum). Interesting features of development of the kidney include a rostral-caudal wave of development, transformation of mesenchyme (nephrogenic cord) into epithelial tissue (nephrons) and formation of transient nephrons in the mesonephros, which plays a role in genital system development.
Development of the kidney and ureter can be divided into four stages:

Pre-nephric stage (weeks 1-5)

During the pre-nephric stage, the embryo produces no urine.

• At the end of the 4th week, the intermediate mesoderm is evident. It gives rise to the nephrogenic cord (urogenital ridge). This mesenchyme will give rise to the adrenal cortices, kidneys, ureters, gonads and reproductive tracts.
• In the 5th week, the nephrogenic cord undergoes segmentation, forming nephrotomes, which will become the mesonephros. (The caudal nephrogenic cord remains unsegmented.) Mesonephric ducts appear dorsolateral to the nephrotomes, which form mesonephric vesicles. The vesicles become glomerular capsules (invaded by capillaries) and tubules, and the ducts extend to reach the cloaca.
• Towards the end of the 5th week, a ureteric bud (metanephric diverticulum) appears on each mesonephric duct and grows to contact the caudal nephrogenic cord (metanephric blastema). Epithelio-mesenchymal interactions between the ureteric bud and nephrogenic cord are important in kidney development.

Mesonephric stage (weeks 6-10)

In the mesonephric stage, transient nephrons in the mesonephros produce urine.

• In the 6th week, the mesonephros begins to produce urine. In the metanephros, embryonic pelvis ("propelvis") and calices ("pseudocalices") appear.
• In the 7th week, the metanephros, which started in the sacral region, has ascended to the lumbar region (perhaps largely due to straightening of the body). The tips of the branches of the ureteric bud induce formation of vesicles in the metanephric blastema. The metanephric vesicles elongate and fuse with ampullae at the end of the ureteric bud. The vesicles develop into nephrons and the ampullae, into collecting tubules.
• By the end of the embryonic period, the mesonephros regresses but a few mesonephric tubules remain. (Some of these will become efferent ductules in males.)

Metanephric stage (fetal period)

By the end of the first trimester, the mesonephros ceases to be a functional kidney and the metanephros begins to produce urine. During the fetal period, the metanephros becomes the definitive kidney.

Postnatal stage

Prior to birth, the placenta is the primary remover of nitrogenous wastes from the fetus. After birth, the kidney takes on this role.

Transverse section of a 2-day-old chick embryo prior to embryo folding showing the intermediate mesoderm (labelled "Wolffian duct"). Gray's Anatomy (1918) figure 19 (originally from Balfour). Source: Wikimedia Commons

Ventral view of the mesonephros and associated structures at about 6 weeks (left is superior and top is lateral). Note the mesonephric tubules (a-d), mesonephric duct (e) and urogenital sinus (x). The ureteric bud should be present at this stage. (The developing gonad (l) and paramesonephric duct (h) are also shown). Gray's Anatomy (1918) figure 1107 (originally from Kobelt). Source: Wikimedia Commons

Transverse section through a urogenital ridge (right is lateral, top is dorsal) of a 4-day-old chick embryo (comparable to human embryo at about 6 weeks). Note the presence of the glomeruli and (Wolffian) tubules of the mesonephros, and the mesonephric (Wolffian) duct. Gray's Anatomy (1918) figure 1106 (originally from Waldeyer). Source: Wikimedia Commons

Bladder and Urethra

The urinary bladder and the proximal urethra are formed chiefly from the ventral portion of the cloaca. Thus the epithelium is endodermal in origin, and the muscle and connective tissue are from splanchnic (lateral plate) mesoderm. The trigone of the bladder may be formed by incorporation of the proximal segments of the mesonephric ducts into the wall of the bladder.
The distal urethra is sexually dimorphic. The different fates in males and females of the definitive urogenital sinus, from which the distal urethra is derived, is described with the development of the external genitalia.

The cloaca and its division

• At the end of the 4th week, embryo folding produces the cloaca, the expanded end of the hindgut. A cloacal membrane marks the end of the hindgut. (In lower vertebrates, the cloaca is the common passage for fecal, urinary and reproductive excretions. In mammalian embryos, the cloaca is divided during development of the anorectum, bladder, urethra and genital systems.)
• In the 5th week, the allantoic diverticulum and mesonephric ducts join to the cloaca. The urorectal septum begins division of the cloaca.
• In the 6th week, the cloaca is divided into the primary urogenital sinus ventrally and the anorectum dorsally by the urorectal septum (which has not quite reached the cloacal membrane).

Development of the primary urogenital sinus

• The entry point of the mesonephric duct is used by anatomists to divide the primary urogenital sinus into the vesico-urethral canal cranially and the definitive urogenital sinus caudally.
• In the 7th week, the proximal mesonephric duct is incorporated into the dorsal wall of the vesico-urethral canal (the future trigone), so that the mesonephric and metanephric ducts enter separately. During further development, these duct openings appear to migrate so that the metanephric duct opening is cranial to the mesonephric duct opening. By the end of the 7th week, the cloacal membrane ruptures. The definitive urogenital sinus becomes continuous with the urethral groove.

Derivatives of the primary urogenital sinus

• The cranial portion of the vesico-urethral canal becomes the urinary bladder.
• The caudal portion of the vesico-urethral canal becomes most of the female urethra or the proximal half of the male’s prostatic urethra.
• The fate of the definitive urogenital sinus is different in males and females. (See Development of Genital Systems.)

The caudal end of a human embryo in the 5th week, showing the cloaca prior to growth of the urorectal septum. Gray's Anatomy (1918) figure 991 (originally from Keibel). Source: WikiMedia Commons

The cloaca and caudal end of the mesonephric (Wolffian) duct at about 5 weeks, showing the ureteric bud (labelled "kidney bud"). Gray's Anatomy (1918) figure 992 (originally from Keibel). Source: Wikimedia Commons

The caudal end of a human embryo at about 6 weeks, showing development of the ureter and metanephros (definitive kidney), and division of most of the cloaca by the urorectal septum to form the primary urogenital sinus and primary anorectal canal. Gray's Anatomy (1918) figure 1116 (originally from Keibel). Source: Wikimedia Commons

The caudal end of a human fetus at about 9 weeks showing complete division of the cloaca. Note the position of the opening of the mesonephric (Wolffian) duct into the primary urogenital sinus inferior to that of the ureter. The mesonephric duct opening marks the boundary between the vesico-urethral canal and the definitive urogenital sinus. Gray's Anatomy (1918) figure 1117 (originally from Keibel). Source: Wikimedia Commons

Selected Malformations of the Urinary System

• Anomalies of amount of renal tissue
  • Renal agenesis
  • Renal hypoplasia
• Anomalies of renal position, form and orientation
  • Renal ectopia (Ectopic kidney)
  • Horseshoe kidney
• Anomalies of renal differentiation
  • Cystic renal dysplasia
  • Polycystic kidney disease
  • Cystic disease of renal medulla
• Congenital anomalies of excretory tract
  • Double, bifid and ectopic ureters
  • Vesicoureteral reflux
  • Urachal anomalies (cysts, sinuses, fistulas)
  • Exstrophy of the bladder and epispadias

External Links

Human Developmental Anatomy Center (HDAC) of the National Museum of Health & Medicine

• O'Rahilly R & Müller F. Developmental Stages in Humans. Carnegie Institution of Washington, 1987.
  

Embryology.ch - an online course in embryology for medical students

Other Resources

O'Rahilly R and Müller F. Human Embryology & Teratology, 3rd Ed. New York: Wiley-Liss, 2001.