Urogenital system

• Urinary system

  Paired kidneys (which excrete urine), paired ureters (which convey urine from the kidneys to the bladder), the urinary bladder (which stores urine temporarily), and the urethra (which carries urine exteriorly)

  
• Kidney development

  1. Begins early during the 4th week of development

  2. Three sets of kidneys will form in the human embryo: Pronephros (1st set), Mesonephros (2nd set), Metanephros (3rd set)

  3. Two sets of kidneys, the pronephros and mesonephros, are not permanent kidneys – they exist for a specific period and later degenerate

  4. The metanephros is the permanent kidney

  
• Pronephros

  • The pronephros is rudimentary and nonfunctional, and resembles kidneys in primitive fishes
  • Appears early in the fourth week
  • Appears as tubular structures in the cervical region
  • Pronephric ducts run caudally and open into the cloaca
  • Pronephros will degenerate
  • Duct system persists, used by the mesonephros
• Mesonephros

  • The mesonephros is well developed and functions briefly, and resembles amphibian kidneys
  • Appears late in the fourth week
  • Caudal to the degenerating pronephros
  • Function as interim kidneys
  • Consists of glomeruli and mesonephric tubules
  • Mesonephros lacks a loop of Henle
  • The duct opens into the cloaca
  • Degenerate at the end of the first trimester

  
• Metanephros

  • Forms the permanent kidney
  • Develops early in the 5th week
  • Begins to function early in the 9th week
  • Consists of Ureteric bud and Metanephric mesoderm (aka metanephrogenic blastema)
  • The ureteric bud is an outgrowth of the mesonephric duct close to its entrance to the cloaca
  • It later acquires a cap of mesoderm (known as the metanephric blastema) derived from intermediate mesoderm

  
• Collecting system development

  1. The ureteric bud will dilate at its cranial end to form the renal pelvis, which divides into cranial and caudal parts to form the future major calyces

  2. Each major calyx will form two new branches, and these buds will continue to branch until there are 12 or more generations of branches

  3. The 2nd order of branches will enlarge and absorb the 3rd and 4th order of branches to form the minor calyces

  4. During further development, the collecting tubules of the 5th and successive collecting tubules will elongate and converge on the minor calyces to form the renal pyramids

  5. Lastly, the ureteric bud will elongate to form the ureters

  
• Excretory system development

  1. The collecting tubules derived from the ureteric bud are covered at the distal end by metanephric blastema (like a cap)

  2. These collecting tubules induce the overlying metanephric blastema to condense

  3. They will form rounded structures known as renal vesicles

  4. The renal vesicles later become S-shaped structures known as primitive nephrons

  5. The proximal part of each nephron will differentiate into a Bowman's capsule. Capillaries will grow into the Bowman's capsule and differentiate into a glomerulus

  6. The distal end of the nephron forms an open connection with the collecting tubules, establishing a passageway between the excretory and collecting systems

  7. The continuous lengthening of the excretory tubules (nephrons) results in the formation of the proximal convoluted tubules, loops of Henle, and distal convoluted tubules

  
• Urine production begins during the 10th week after the differentiation of glomerular capillaries
• Ascent of the kidney

  1. The permanent kidney forms in the pelvic region and later migrates to a more cranial area in the abdominal cavity

  2. The ascent of the kidney results mainly from the growth of the embryo's body caudal to the kidneys: the caudal part of the embryo grows away from the kidney, such that the kidneys progressively occupy more cranial levels

  3. As the kidneys migrate from the pelvis, they receive their blood supply from vessels that are close to them

  4. Initially, the renal arteries are branches of the common iliac arteries

  5. As the kidneys migrate further, they receive their blood supply from the distal aorta

  6. When the kidneys reach a higher level, they receive new branches from the aorta

  7. Normally the caudal branches degenerate

  8. When the kidneys come into contact with the suprarenal glands in the 9th week, their ascent will stop

  9. Upon cessation of their ascent, the kidneys receive their most cranial arterial branches from the abdominal aorta – which become the permanent renal arteries

  10. Initially, the hilum faces ventrally (anteriorly), but as the kidneys ascend, they will rotate by 90 in a medial direction

  11. By the 9th week, the hilum will be directed medially
• Kidney abnormalities

  • Accessory renal arteries
  • Renal agenesis
  • Ectopic kidneys
  • Malrotated kidney
  • Horseshoe kidney
  • Duplication of the ureters
• Accessory renal arteries

  • About 25% of adult kidneys have 2-4 renal arteries known as accessory or supernumerary renal arteries
  • These arteries arise from the aorta superior or inferior to the main renal artery
  • Accessory renal arteries may enter kidneys directly at the superior/inferior poles
  • Those that enter the inferior pole may cross anterior to the ureter and obstruct it, causing the accumulation of urine at the renal pelvis
  • This is known as hydronephrosis and causes the distention/enlargement of the renal pelvis

  
• Renal agenesis

  • Affects approximately 1:1000 newborn infants
  • Males are affected more often than females
  • Left kidney is usually the one that is absent
  • Unilateral renal agenesis often causes no symptoms due to compensatory hypertrophy, wherein the other and performs the function of the missing kidney
• Malrotated kidney

  • The hilum will face anteriorly if a kidney fails to rotate medially at 90
  • If the hilum faces posteriorly, it means that the rotation of the kidney proceeded too far
  • If the kidney faces laterally, then lateral (instead of medial) rotation took place
• Crossed renal ectopia

  • A double kidney may occur if the ureteric bud is duplicated
  • Sometimes during the ascent of the kidneys, one kidney may cross to the other side – with or without fusion with the other kidney – resulting in a condition known as crossed renal ectopia
• Ectopic kidneys

  • If one of the kidneys fails to ascend, it is called a pelvic kidney because it remains in the pelvic region
  • If the lower poles of the kidneys fuse and form a horseshoe shape, hence this condition is known as a horseshoe kidney
  • A horseshoe kidney is prevented from ascending by the branch of the inferior mesenteric artery
• Bladder development

  1. In the formation of the anal canal, the urorectal septum divides the cloaca into the urogenital sinus anteriorly and the rectum/anorectal canal posteriorly. The urogenital sinus forms the urinary bladder

  2. Initially, the urinary bladder is continuous with the allantois. Later the allantois is closed off by a fibrous cord called the urachus

  3. The urachus will connect the apex of the bladder with the umbilical cord. In the adult, the urachus is known as the median umbilical ligament
• Bladder abnormalities

  • If the urachus doesn't form, a urachal fistula will occur
  • If the urachus doesn't form completely, a urachal cyst/sinus will occur

  
• Indifferent gonads

  • The mesothelium on the medial side of the mesonephros thickens. The thickening of this mesothelium alongside the underlying mesenchyme forms a bulge on the medial side of the mesonephros. This bulge is known as the gonadal or genital ridge
  • The gonads are derived from the mesothelium, underlying mesenchyme, and primordial germ cells
• Primordial germ cells

  • The primordial germ cells are the primitive sex cells. They appear early in the 4th week of development near the origin of the allantois
  • These cells will migrate along the dorsal mesentery of the hindgut to the gonadal ridges, which they enter during the 6th week of development
• Primary sex cords

  • Finger-like projections known as the primary sex cords will form on the genital ridge
  • The primary sex cords will extend into the underlying mesenchyme
  • As the primordial germ cells enter the gonadal ridges, they get incorporated into the primary sex cords
• Sex determination

  • Prior to the seventh week of IUL, the gonads of the two sexes are identical and are called indifferent gonads
  • The SRY gene located on the short arm of the Y-chromosome is a Testis Determining Factor (TDF)
  • The SRY gene acts as a switch which directs the development of the indifferent gonad into a testis
  • Under the influence of TDF, primary sex cords will differentiate into seminiferous tubules
• Seminiferous cords

  • The presence of TDF induces the primary sex cords to condense and extend into the mesenchyme of the indifferent gonad. Here, they will branch and anastomose to form the seminiferous cords
  • The absence of TDF results in the formation of ovaries
  • The seminiferous cord will separate from the epithelium of the developing testis
  • Then, a thick fibrous capsule, the tunica albuginea, will develop
  • The developing testis will then separate from the degenerating mesonephros
• Development of the testis

  1. As the connection between the developing testis and the degenerating mesonephros is lost, the testis becomes suspended by its own mesentery, the mesorchium

  2. The seminiferous cords will develop into seminiferous tubules, tubuli recti, and the rete testis

  3. The seminiferous tubules are separated by mesenchyme, and this mesenchyme will give rise to the interstitial cells of Leydig

  4. By the 8th week these cells begin to secrete testosterone

  5. In addition, the fetal testes produce a glycoprotein known as antimullerian hormone or Mullerian inhibiting substance
• Effect of AMH

  AMH is produced by the Sertoli cells; it suppresses the development of the paramesonephric (mullerian) duct
• Further development of the testis

  1. Seminiferous tubules remain solid until puberty when lumen starts to form

  2. Sertoli cells and spermatogonia form walls of seminiferous tubules

  → Sertolli cells derived from the testis surface epithelium; Spermatogonia derived from primordial germ cells

  3. Rete testis connects to 15-20 mesonephric tubules which become efferent ductules

  4. Efferent ductules connect to mesonephric duct which later becomes ductus epididymis

  5. Mesonephric duct, distal to epididymis, acquires a thick investment of smooth muscle and becomes the ductus deferens
• Development of the ovaries

  1. Primary sex cords extend into mesenchyme to form non-functional rete ovary (later degenerates with primary sex cords)
  2. Secondary sex cords (SSCs) appear on surface epithelium and extend into mesenchyme
  3. As the SSCs increase in size, primordial germ cells get incorporated into secondary sex cords
  4. The SSCs break into isolated clusters of primordial follicles at 16 weeks
  5. Each follicle contains an oocyte (oogonium) derived from primordial germ cells
  6. Follicles are surrounded by a single layer of follicular cells derived from sex cord and increase due to mitosis.
• Descent of the testis

  1. Testis forms on medial side of mesonephros and must descend into scrotum

  2. Testis is retroperitoneal and descends in retroperitoneal space

  3. Reaches internal inguinal ring by 12th week

  4. Gubernaculum develops, attaching to caudal pole of testis and internal surface of labioscrotal swellings

  5. Processus vaginalis forms along gubernaculum from internal ring to labioscrotal folds

  6. Testis descends posterior to processus vaginalis, guided by gubernaculum through inguinal canal

  7. Testis reaches external inguinal ring just before birth and enters scrotum a few days after birth
• Cryptorchidism

  Failure of testis to descend into scrotum, may be unilateral or bilateral, results in sterility if both testes remain in abdomen
• Descent of the ovaries

  1. Ovaries descend from posterior abdominal wall to pelvis just inferior to pelvic brim

  2. Gubernaculum forms, cranial part becomes ovarian ligament, caudal part forms round ligament of uterus which passes through inguinal canals to labia majora
• Development of female genital ducts

  1. During the 5th and 6th weeks, the genital system is indifferent with two pairs of genital ducts present: the paramesonephric ducts and mesonephric ducts.

  2. The mesonephric ducts play an important part in the male reproductive system

  3. The paramesonephric duct plays an important role in the female reproductive system
• Development of external genitalia

  1. Mesenchymal cells migrate around cloacal membrane to form cloacal folds

  2. Cloacal folds fuse anteriorly to form genital tubercle

  3. Cloacal folds subdivide into urethral folds anteriorly and anal fold posteriorly

  4. Genital swellings form on each side of urethral folds
• Development of male external genitalia

  1. Genital tubercle elongates into phallus, pulling urethral folds forward to form urethral groove

  2. Urethral groove epithelium forms urethral plate

  3. Urethral folds close over urethral plate to form penile urethra, not extending to tip

  4. Distal urethra formed by ectodermal cells penetrating inward

  5. Genital swellings form scrotum by moving caudally and fusing
• Development of female external genitalia

  1. Genital tubercle forms clitoris

  2. Urethral folds form labia minora

  3. Genital swellings form labia majora

  4. Urogenital groove remains open, forming vestibule of vagina
• Hypospadias

  Most common anomaly of penis, occurs when fusion of urethral folds is incomplete, resulting in abnormal urethral openings

  >There are four main types: glanular, penile, penoscrotal & perineal hypospadias
• Types of hypospadias

  • Glanular hypospadias (most common): external urethral orifice is on the dorsal surface of the glans of the penis
  • Penile hypospadias: external urethral orifice is on the dorsal surface of the body of the penis
  • Penoscrotal hypospadias: urethral orifice is at the junction of the penis and scrotum
  • Perineal hypospadias: labioscrotal folds fail to fuse and the external urethral orifice is located between the unfused halves of the scrotum
• Glanular and penile hypospadias constitute approximately 80% of cases
• Agenesis of external genitalia

  Congenital absence of penis or clitoris, results from failure of genital tubercle to develop, urethra opens into perineum near anus
• Absence of vagina and uterus

  Occurs in 1:5000 female births, results from failure of sinovaginal bulbs to develop and form vaginal plate, uterus is usually absent
• Vaginal atresia

  Failure of canalization of vaginal plate results in blockage of vagina
• Ureteric bud/diverticulum forms the collecting system of the kidneys (ureters, renal pelvis, major and minor calices, collecting tubules and ducts