Urogenital Development

Urogenital Development

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Last updated 30 March 2006

This page was contributed by David Boshell

Urogenital Development

Development of the kidney

The pronephros

The pronephroi or cervical nephrotomes are a series of transient, non-functional vesicles that develop in the cervical intermediate mesoderm, appearing, and then degenerating in the 4^th week.

The mesonephros

Pairs of mesonephroi develop, mainly in the thoracic and upper lumber intermediate mesoderm in the 4^th and 5^th weeks, forming a group of about 20 pairs, and will eventually form part of the male genital system.

Each mesonephos is drained by a mesonephric duct, which forms from the lateral margin of the intermediate mesoderm on day 24, growing caudally to open into the ventrolateral wall of the cloaca (the future dorsal wall of the bladder), and will also form part of the male genital system.

The mesonephroi will regress after the 10^th week, but from the 6^th week onwards, they function in excretion, via mesonephric excretory units.

Each mesonephric excretory unit develops from a vesicle into a mesonephric tubule, with one end expanding to form a Bowman’s capsule around a capillary glomerulus, and the other end fusing with the mesonephric duct.

The metanephros

In the 5^th week, the caudal part of each mesonephric duct sprouts a ureteric bud that grows into a zone of sacral intermediate mesoderm called the metanephric blastema, and will induce the mesoderm to form a metanephros (definitive kidney)

The metanephric blastema induces the ureteric bud to begin branching, whilst the branches of the ureteric bud, with expanded tips (ampullae), induce the metanephric blastema to grow blastemic caps around them.

As the ureteric buds branch and gain their blastemic caps, the kidney becomes lobulated in appearance, with each metanephros having about 15 lobes by 16 weeks.

Some parts of the kidney are formed by further branching, whilst other parts are formed by the coalescence of branches:

Kidney differentiation
Kidney structure	Formed by…
Renal pelvis	Expansion of the first 2 branches of the ureteric bud
Major calyces	The next 4 generations of branching
Minor calyces	Coalescence of the next 4 generations
Collecting ducts	An additional 11 generations of branching

The metanephric excretory units (the future nephrons) arise from the blastemic caps surrounding the ampullae of the collecting duct branches, developing in the same manner as the mesonephric excretory units:
A nephric vesicle lengthens into nephric tubule, with:
One end expanding into a Bowman’s capsule, surrounding a glomerulus, forming the renal corpuscle

The other end forming the proximal convoluted tubule, loop of Henle and distal convoluted tubule, which connects with the collecting duct in week 10 to begin functioning.

Neurons from the kidney are derived from neural crest.

Between weeks 6-9, the kidneys ascend to their final location, inferior to the adrenal glands, supplied by transient aortic sprouts, with the final pair becoming the renal arteries.
Failure of the kidneys to ascend, due to, for example, fusion of the kidneys at their inferior lobes (horseshoe kidney) results in pelvic kidney.

The kidney has differentiated by week 15.

Development of the urinary tract

After the kidney, the remainder of the urinary tract is derived from hindgut endoderm.

The primitive urogenital sinus (the ventral division of the cloaca), has 3 parts:

The presumptive bladder cranially, continuous with the allantois
An intermediate narrowing called the pelvic urethra.
The definitive urogenital sinus caudally, bounded by the urogenital membrane (the ventral division of the cloacal membrane)

In weeks 4 –6, the mesonephric ducts flare open and become incorporated into the dorsocaudal wall of the presumptive bladder, creating a triangular area of mesoderm called the trigone.
The orifices of the ureteric buds (future ureters) become positioned at the craniolateral corners of the trigone, whilst the mesonephric ducts migrate caudally to the apex of the trigone, opening into the pelvic urethra.
The endodermal lining of the rest of the bladder wall migrates to cover the inner aspect of the trigone, and the mesoderm associated with the bladder wall forms the smooth muscle of the bladder.

The pelvic urethra and definitive urogenital sinus differentiate according to gender:

Sex	Embryological structure	Adult structure
Males	Pelvic urethra	Membranous and prostatic urethra
Males	Definitive urogenital sinus	Penile urethra
Females	Pelvic urethra	Membranous urethra
Females	Definitive urogenital sinus	Vestibule of the vagina

Development of the genital system

The primordial germ cells develop from the endoderm of the definitive yolk sac, migrating to the dorsal body wall in weeks 4 - 6, inducing the coelomic epithelium to grow and differentiate.

The primitive sex cords develop from cells of the mesonephros and coelomic epithelium of the urogenital ridge, originally present in both the cortical and medullary parts of the presumptive gonad (the future testis/ovary).

In the 6^th week, the paramesonephric (Müllerian) ducts form by invagination of a groove in the coelomic epithelium, developing in the basement membrane of the adjacent mesonephric ducts.
Their cranial ends remain open to the peritoneal cavity, whilst their caudal ends fuse with the pelvic urethra, medial to the openings of the mesonephric ducts.

Cortical and medullary sex cords, and mesonephric and paramesonephric ducts are present in both sexes during the ambisexual (indifferent) phase of sexual development, with lasts until the end of the 6^th week.

Sex in humans is determined by the presence or absence of testes-determining factor (TDF), encoded by the sex-determining region of the Y chromosome (SRY), which, if present, will give rise to a male (46XY), and if absent, will default to a female (46XX).
Thus, female development takes place when male determining substances are absent.

Male development

The 1^st stage of male development occurs in the 7^th week, with the cells of the medullary sex cords differentiating into pre-Sertoli cells, in response to the expression of TDF, and the cortical sex cords degenerating.

The pre-Sertoli cells become organised into testis cords (future seminiferous tubules), which, in close contact to primordial germ cells, prevent them from maturing into spermatogonia.

Distal to the germ cell region, the testis cords differentiate into the rete testis.

The 2^nd stage of male development is controlled by antimüllerian hormone (AMH, or müllerian inhibiting substance – MIS), secreted from pre-Sertoli cells.

AMH:

Causes regression of the paramesonephric ducts, leaving behind the appendix testis and the prostatic utricle as remnants of this duct in the adult male
Probably induces the differentiation of Leydig cells from the urogenital ridges, that secrete testosterone initially under the control of hCG from the placenta, and later under the control of LH from the pituitary gland.

The 3^rd stage of male development occurs in response to mainly 2 male sex steroid hormones (androgens):

Testosterone, inducing male differentiation of the mesonephric ducts, and some other structures, and puberty (in a large surge).

Dihydrotestosterone, inducing male differentiation of the external genitalia, and some other structures.

The male genital duct system develops from the mesonephric duct, and some mesonephric tubules near the gonads:

Male genital duct development
Embryological structure	Mature structure
Mesonephric duct	Duct of epididymis and ductus deferens Appendix epididymis Seminal vesicles and Ejaculatory ducts
Epigenital mesonephric tubules (adjacent to testes)	Efferent ductules
Urethra	Prostate and bulbourethral glands

Female development

The primitive sex cords degenerate, and a secondary group of cortical sex cords is formed, that invest the primordial germ cells, arresting their development at the 1^st meiotic division.

These primary oocytes are invested by a layer sex cord (follicle) cells, forming primordial follicles that will one day undergo folliculogenesis after menarche, under the influence of gonadotropin levels controlling each menstrual cycle.

In the absence of AMH, the paramesonephric ducts will give rise to the oviducts, uterus and superior vagina, whilst the mesonephric ducts and tubules will degenerate, leaving behind the small vestiges near the ovaries and Gartner’s cysts near the cervix.
The female genital duct system develops from the paramesonephric ducts, except for the caudal vagina, which develops from the posterior wall of the pelvic urethra:
- The dorsal wall of the pelvic urethra forms a sinusal tubercle where the mesonephric ducts make contact with it.
- Caudally, the paramesonephric ducts fuse together, starting at the sinusal tubercle, to form the uterovaginal (genital) canal, which further develops into the uterus and superior part of the vagina.
- Cranially, the paramesonephric ducts stay separate, forming the oviducts.
- The sinusal tubercle expands into vaginal bulbs which canalise to form the inferior part of the vagina, which than migrates onto the definitive urogenital sinus, which becomes the vestibule of the vagina.
- The vaginal lumen is initially separated from the vestibule by a barrier of tissue that breaks down in the 5^th month, leaving behind the hymen as its remnant.

Development of the external genitalia

The sexes are visibly distinct in the 4^th month.

A pair of cloacal folds develop on either side of the cloacal membrane, meeting ventrally to form the genital tubercle.

Fusion of the urorectal septum with the cloacal membrane in the 7^th week creates the perineum, dividing the cloacal membrane into the urogenital and anal membranes, and the similarly dividing the cloacal folds into ventral urethral (urogenital) folds and dorsal anal folds.

Labioscrotal swellings develop lateral to the urethral folds.

The urogenital membrane breaks down in the 7^th week.

The genital tubercle elongates to form the phallus, which is divided by a coronary sulcus into a glans (the future glans penis/clitoris) and a shaft.

In the male, the endodermal urethral plate becomes excavated, forming a urethral groove reaching as far as the glans, flanked by extensions of the urethral folds.
The penile urethra in the shaft of the penis is formed by zippering up of the urethral folds, whilst the portion in the glans develops from an epidermal invagination at the tip of the glans.
The scrotum is formed by fusion of the labioscrotal swellings.

In the female, the lanioscrotal swellings become the labia majora; the urethral folds become the labia minora and the genital tubercle forms the glans and shaft of the clitoris.

Descent of the gonads

The testes and ovaries descend under the control of a gubernaculum: a ligament that condenses out of sebserous fascia in the 7^th week.

Its superior end attaches to the gonad, whilst its inferior, expanded end, the gubernacular bulb, attaches to the deep fascia between the internal and external oblique muscles in the region of the labioscrotal folds.

The inguinal canals develop next to the gubernacular bulbs when, in the 7^th week, the processus vaginalis (vaginal process), next to the gubernacular bulb, evaginates into the abdominal wall.
In the male, they covey the testes into the scrotum, with everted abdominal wall layers becoming spermatic fascia, ensheathing the spermatic cord.

In the male, the testes descend via shortening of the gubernaculum to the deep inguinal ring by the 3^rd month, pause until the 7^th month, and then continue down into the scrotum by the 9^th month.

In the female, the gubernacula do not shorten, but form a connection with the paramesonephric ducts where the two structures cross.
The subsequent formation of the uterovaginal canal from the caudal portions of the paramesonephric ducts also creates the broad ligaments of the uterus and pulls the ovaries into them.
The gubernacula form the ovarian ligaments, and the round ligaments of the uterus.

The inguinal canal normally closes after birth, and, in males, the inferior part of the processus vaginalis remains patent, forming a ventral sac around each testis called the tunica vaginalis.
In both sexes, the processus vaginalis may remain patent, allowing abdominal organs to herniate into the inguinal canal, forming an indirect inguinal hernia.