Development of the Genitourinary System
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Introduction
The development of the urinary system and genital systems are closely linked. The urogenital system develops from intermediate mesoderm. A longitudinal elevation - the urogenital ridge - forms on each side of the dorsal aorta, with the nephrogenic cord leading to the urinary system and the gonadal ridge leading to the genital system.
The urogenital system develops from intermediate mesoderm. A longitudinal elevation - the urogenital ridge - forms on each side of the dorsal aorta, with the nephrogenic cord leading to the urinary system and the gonadal ridge leading to the genital system.
Kidney Development
Three sets of kidneys develop in human embryos:
- pronephric kidneys appear early in the 4th week and form ducts that run to the cloaca
- mesonephric kidneys use pronepnric ducts to develop mesonephric ducts, which become efferent ductules of the testes
- metanephric kidneys develop from from a metanephric mass of intermediate mesoderm, induced by the ureteric bud (metanephric diverticulum), an offshoot from the mesonephric duct. These permanent kidneys begin functioning in the 9th week.
The ureteric bud/metanephric diverticulum is the beginning of the ureter, renal pelvis, calices, and collecting tubules.
Straight collecting tubules undergo repeated branching to form successive generations of tubules.
The end of each new collecting tubule induces clusters of mesenchymal cells to form small metanephric vesicles, which then elongate to form renal tubules and fuse with the collecting duct. The proximal ends are invaginated by glomeruli.
Each functional unit is therefore composed of two mesenchymal tissue types - the collecting duct from metanephric diverticulum and the nephron from metanephric mesoderm. Mesenchymal-to-epithelial transition is all over the place in the kidney.
Fetal kidneys are divided into lobes, which usually disappear as nephrons increase and grow. At term, each kidney contains 800,000 - 1,000,000 nephrons.
Kidney Ascent
Metanephric kidneys begin close to each other in the pelvis. As the embryo grows, they come to lie in the abdomen and move into the abdomen, primarily due to the caudal end of the embryo growing away from the kidneys. During 'ascent' ,the kidneys' blood supply changes, with caudal branches undergoing involution. When the kidneys come into contact with the adrenal glands their ascent stops, and renal arteries become permanent.
Collecting System Development
The metanephric diverticulum, or ureteric bud, is the beginning of the ureter, renal pelvis, calices, and collecting tubules.
At the end of the 4th week, embryo folding produces the cloaca, or expanded hindgut. In the 5th week, the allantoic diverticulum and mesonephric ducts join the cloaca, while the urorectal septum (extraembryonic mesoderm) begins to divide the cloaca into the urogenital sinus and anorectum.
Bladder Formation
The urogenital sinus is then considered divided into the vesicourethral canal and the definitive urogenital sinus. The bladder is formed primarily from the vesicourethral canal, which also contributes to the urethra. The definitive urogenital sinus (the phallic part) forms portions of the genitalia.
The proximal mesonephric duct becomes incorporated into the dorsal wall of the urogenital sinus, forming the trigone. Mesonephric and metanephric ducts enter separately.
The urethra
The urethra is derived from endoderm of the urigenital sinus
Division of cloaca
cloaca becomes separated to form urogenital sinus and anorectal canal (check these)
Common Gonad Development
The mesenchymal gonadal ridge is soon joined by fingerlike epithelial cords, producing the indifferent gonad with a cortex and medulla. In females, the cortex differentiates into an ovary, while in males the medulla differentiates into the testes.
By the 6th week, the cloacal membrane forms the primary urethral groove, bounded by primary urethral (urogenital) folds. Genital (labioscrotal) swellings occur on either side and the genital tubercule ventral to it. Sexual differentiation of the external genitalia begins to occur in the 1oth week.
Primordial Germ Cells
Primordial germ cells originate in the yolk sac and migrate through the gut to gonadal ridges during the 6th week.
Sex Determination
The presence of a Y chromosome, with the SRY gene for testis-determining factor, induces male differentiation.
Female Genital Development
Absence of SRY gene and therefore testosterone and MIS leads to development of outer genitalia and Mullerian ducts and regression of Wolffian ducts.
Ovary
The gonadal cord cortex forms folliculogenous cords, and primordial germ cells form oogonia. During the second trimester oogonia enter meiosis I and become surrounded by follicular cells, forming primordial ovarian follicles. Meiosis I completes during ovulation, while meiosis II occurs following fertilization.
Paramesonephric (Mullerian) duct
Two Mullerian ducts form and fuse to form the uterus, cervix, and upper vagina, with proximal, unfused tubes becoming the uterine tubes.
in the presence of anti-Mullarian hormone/Mullerian inhibiting factor, produced by Sertoli cells, the paramesonephric ducts regress
External genitalia
The genital tubercle becomes the clitoris, the genital swellings become labia majora, and urethral folds become labia minora.
Male Genital Development
testis
Under the influence of TDF, the gonadal ridge medulla differentiate into testicular cords containing prospermatogonia and future Sertoli cells. Interstitial Leydig cells begin secreting androgens early in the fetal period, leading to masculine differentiation of internal and external genitalia.
Mesonephric tissue grow into the medulla and form rete testis, while mesonephric tubules form efferent ductules connecting the rete testis to the duct of the epididymis.
Descent of the testes usually occurs during the third trimester and is androgen-dependent.
Wolffian (mesonephric) Duct
Mesonephric ducts develop in the 5th week, and in the presence of androgens, the epididymis, ductus deferens, seminal vesicle, and ejaculatory duct form. The mesonephric duct degenerates in females.
External genitalia
In the presence of androgens, the genital tubercule becomes the penis, the urethral folds form the ventral shaft, and the genital swellings fuse to form the scrotum.
Flash animation of penis development
SRY Gene
- presence of SRY gene (and associated genes), which codes for testis-determining factor, on Y chromosome induces primordial gonads to differentiate into fetal testes: Sertoli cells and Ledig cells
- Ledig cells produce testosterone, inducing Wolffian duct structures and external genetalia
- Sertoli cells produce Mullarian-inhibiting substance (MIS) which induces regression of Mullerian ducts
Effect on Brain
- there are differences in brains re: ie reading tasks
- there are differences in neurological/psychiatric disorders differentially affecting men and women
- different responses to various medications
- there appear to be sexual dimorphism in hypothalamus, including in brains of homosexuals
- could be genes, could be hormones....
Congenital Urinary System Problems
Renal agenesis
- unilateral is 1:1000; other kidney usually hypertrophies and compensates
- bliateral agenesis is associated with oligohydramnios due to lack of urine production. babies with no kidneys rarely survive longer than a few months.
Renal hypolasia
- unilateral is 1:500 adults
both can be asymptomatic
Potter Syndrome - bilateral renal agenesis
Renal ectopia
- asymptomatic, but can cause problems during pregnancy with compression of an abdominal kidney
Horseshoe kidney
- kidneys fuse and become 'caught' by the inferior mesenteric artery
- often asymptomatic, but can have increased pyelonephritis (as is lower) and kidney stones
cystic renal dysplasia
- problem with differentiation; kidney contains primitive ducts and nonrenal tissues such as cartilage, fat, hematopoietic tissue, and cysts
polycystic kidney disease
- autosomal dominant disease - occurs later in life, with an incidence of 1:700; cysts form from all segments of nephron
- autosomal recessive disease occurs in infancy and has high mortality, incidence of 1:5,000; cysts form in collecting ducts
cystic disease of renal medulla
- presence of multiple medullary cysts, cortical tubular atrophy, interstitial fibrosis. Can result in renal failure.
double, bifid, ectopic ureters
- double = double
- bifid = branched ureteric bud leads to partial ureteric duplication
- ectopic = ureter opens in area other than trigone; ie in urethra or vagina, prostate or seminal vesicle
vesicoureteral reflux
- abnormal flow of urine back into ureters; can be caused by bladder/ureter valve problem, or blocked ureter
- can cause pyelonephritis, direct damage to kidney
- common in children with UTI
urachal anomalies
- the urachus develops from the allantois, an extension of the urogenital sinus, and connects the bladder and umbilicus but degenerates at birth
- lack of degeneration can lead to infection, urine leakage, or cyst formation
extrophy of bladder
- malformation of bladder, which is turned inside out, flattened, and exposed to the outside
epispadias
- rare penis problem in which urethra opens on the dorsal side
Resources and References
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