(Transcribed from Dr. Kalliecharan’s lecture, 4 April 2000 by Brian Buschman)
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The urinary and genital systems have a common developmental route beginning from the urogenital ridge which comes from intermediate mesoderm. On both sides the urogenital ridge becomes the nephrogenic cord/ridge and the gonadal/genital ridge which will develop into the urinary and genital systems respectively.
In the embryo there are three different kidneys that develop in a sequence with only the last ones persisting. The first one, the pronephros, begins to develop around the beginning of the fourth weeks and begins to regress around the end of the fourth week. It develops a duct system but it never becomes functional.
As the pronephroi is regressing the mesonephroi is developing. It forms functional nephrotic tubules that act as an interim kidney and empty into the mesonephric duct. The mesonephroi is located directly lateral to the developing gonad and together they form the urogenital ridge.
This is the permanent kidney which begins to develop around the fifth week. About a month later it takes over renal function from the mesonephroi. It develops from two closely related structures, the ureteric bud (or metanephric diverticulum) and the metanephric mesoderm. The collecting system will develop from the ureteric bud. The ureteric bud pushes into the metanephric mesoderm which gives the ureteric bud a metanephric tissue cap. The ureteric bud will then develop into the collecting ducts and tubules of the pyramids, the calyces, the renal pelvis and the ureter. That newly formed metanephric tissue cap will develop into the renal tubules that are attached to the collecting ducts. These renal tubules will develop into the nephrons.
The kidney’s first develop in the pelvis and ascend to their current position. Their blood supply branches off the aorta and as they go they form new arteries and veins. As adult may end up with two or three sets of renal vessels if the premature vessels persist after birth.
Renal agenesis results when the ureteric bud does not reach the metanephric mesoderm. Unilateral agenesis is rather common and is not a big problem. Bilateral is fatal.
Horseshoe shaped kidneys are the result of fusion of the inferior poles. When they ascend from the pelvis they get stuck on the inferior mesenteric artery and stay at that point.
Ectopic kidneys may be located in an abnormal position or may fail to rotate. This usually results in a pelvic kidney with or without a ventrally pointing pelvis.
Duplication of the urinary tract occurs when the ureteric bud splits early in the stages of development. The individual will have two kidneys and ureters on the given side.
Ectopic ureter is when the ureter opens somewhere that it should not. It’s most common in cases of double ureter and the extra often opens into the vagina or the male urethra.
The urinary bladder begins with the urorectal septum giving the anal canal and the urogenital sinus. The urogenital sinus will form into:
1) The upper part becomes the urinary bladder. The allantois was connected here and degenerates to give the uranchus in the median umbilical ligament.
2) The middle part gives males their prostate and membranous urethra.
3) The lower, phallic part, gives some urethra.
The mesonephric ducts and ureters enter the bladder. As the metanephric kidney’s ascend the ureters migrate superiorly on the bladder. The mesonephric ducts migrate inferiorly and become the ejaculatory ducts in males.
The trigone is the triangle located between the entrances of the mesonephric ducts and the ureters. It’s mucosa is of mesodermal origin. The rest is endoderm. Eventually the mesoderm of the trigone is replaced by endoderm.
The mucosa of the urethra is endoderm in the female and in the proximal part of the males. The muscular layer is mesodermal in origin. The distal part of the male urethra is ectoderm from the gland penis.
The gonads begin to develop as an undifferentiated (not yet male or female) genital ridge medial to the metanephric kidney. The gonads develop from:
1) Mesothelium of the posterior abdominal wall.
2) Mesenchyme cells.
3) Primordial germ cells.
Initially tubes called the primary sex cords develop in the gonads and are in contact with the surface epithelium. Some of these cords wind through the cortex and some through the medulla. At this stage primordial germ cells migrate into the primary sex cords from the allantois.
The genotype XY the Y chromosome has the role of testis determining factor (TDF) that stimulates the medullary cords to further develop and those of the cortex to regress. The testis will produce testosterone which causes the development of male sexual characteristics. Without testosterone, regardless of genotype or presence of a female gonad, a female will develop. Except in anomalies if one of the chromosomes is a Y the baby will develop male regardless of the number of X chromosomes present.
The Y chromosome causes TDF to induce the formation of the seminiferous cords. They loose contact with the epithelia as it forms a dense fibrous tunica albugenia. As the testis enlarge they become suspended from it’s mesentery, the mesorchium.
Seminiferous tubules have spermatogonia and supporting cells. The supporting cells include Sertoli cells and Leydig cells. Sertoli cells secrete Mullerine-inhibiting factor which suppresses the development of the paramesonephric duct (to be discussed soon). Leydig cells produce testosterone when stimulated by LH.
In the female gonad the medullary sex cords regress and become a vascular stroma. The secondary (or cortical) sex cords develop which supply the cortex with oogonia. Around each oogonia a simple squamous layer of follicular cells develop. The germinal epithelium becomes surrounded by a fibrous tunica albugenia. The ovary also becomes suspended by a mesovarium.
Initially both genders have a pair of mesonephric and paramesonephric ducts. Originally the mesonephric duct was the drainage duct of the mesonephric kidneys. The paramesonephric ducts have an open, funnel-shaped end, and develop as structures paired with the mesonephric ducts. The paramesonephric ducts join inferiorly to form the uterovaginal primordium, a Y shaped structure that will give the uterus and superior vagina in females.
The male testis produce testosterone in the Leydig cells and Mullerian inhibiting substance in the Sertoli cells. The Mullerian inhibiting substance causes the paramesonephric ducts to regress. Testosterone causes the mesonephric ducts to persist and to develop into the epididymis and ductus deferens.
The accessory glands, seminal vesicles, prostate and bulbourethral glands all develop out of their associated ducts. This is also induced by testosterone.
In the presence of ovaries or no gonads the fetus develops female. Without testosterone the mesonephric duct regresses. The paramesonephric duct persists. It’s cranial part becomes the uterine tube and the inferior part the uterovaginal primordium. When the two paramesonephric ducts fuse to give the uterovaginal primordium the fusion brings the two ligaments together that form the broad ligament of the uterus.
Two outgrowths come from the urovaginal primordium called the sinovaginal bulbs. They fuse to form the vaginal plate. It is joined by cells of the urovaginal sinus that canalize to give the vagina. The superior third develops from the paramesonephric ducts and the inferior two-thirds from the urogenital sinus. The paramesonephric duct and the urogenital sinus are separated by the hymen which ruptures during development. After birth only a thin mucus membrane persists in the vaginal vestibule.
Double uterus is when the vagina and uterus are both appearing double due to improper formation of the urovaginal primordium.
Bicornate uterus is similar with two uterus horns that join and have a single vagina.
Unicornate uterus is when only one paramesonephric duct developed so only half of the uterus exists.
Atresia of the vagina is the failure of the vagina to canalize.
Atresia of the cervix is when the cervix fails to canalize.
The gubernaculum descends from the gonad to the labioscrotal swelling. The peritoneum evaginates through the abdominal wall parallel to the gubernaculum and is called the process vaginalis. The process vaginalis carries with it the layers of the abdominal wall that it traverses.
The retroperitoneal testis move to their scrotal location in three phases:
1) Initial movement is caused by enlargement of the testis and degeneration of the mesonephric kidney.
2) Regression of the paramesonephric ducts help guide the kidney to the level of the external inguinal ring.
3) The gubernaculum guides the testis into the scrotum. It is not know if the gubernaculum actually pulls them down or if it holds them in place and all the other structures enlarge around them.
This path is the explanation for the posterior abdominal wall origin or the neurovascular supply of the testis.
The ovaries descend from their retroperitoneal position to their adult locations. The gubernaculum becomes both the ovarian ligament and the round ligament of the uterus.
Originally genitalia development begins the same way. Mesenchyme cells produce a genital tubercle and the urogenital membrane divides down the middle to give two urogenital folds.
Under the influence of testosterone the genital tubercle becomes the penis. The labioscrotal swellings enlarge to fuse and form the scrotum.
The genital tubercle becomes the clitoris. The urogenital folds grow to form the labia minora. The labioscrotal folds enlarge to form the labia majora. The urogenital sinus gives the vestibule of the vagina.
Occasionally there can be a difference between a person’s genotype and phenotype. The gonad usually develops according to the proper sex but other things can go wrong.
a) True hermaphrodites are 46, XX and have both male and female gonads. Their external genitalia is somewhat ambiguous. They are raised to be female as they appear as female with an enlarged clitoris.
b) Female pseudohermaphroditism, 46, XX, will have ovaries but will develop as a male due to excessive androgen stimulation either from the maternal drugs or overproduction of the adrenal glands.
c) Male pseudohermaphroditism, 46, XY, usually have stunted development of the external male genitalia.
Gonadal dysgenesis involves the degeneration of the gonads and the individual develop female. It is usually associated with Turner’s syndrome (45, XO).
This disease is 46, XY, but have a shortage of working androgen receptors. The paramesonephric ducts are missing because of the production of anti-Mullerian substance but the lack of action of testosterone leads to the development of female external sexual characteristics.
Failure of the urethral folds to fuse properly which results in an opening of the urethra on the ventral side of the penis.
It is similar to hypospadias with a dorsal opening.
Testis remain on the posterior abdominal wall. The man will be sterile because the testicular temperature will be too high to produce viable sperm.
If the process vaginalis persists after birth in a male they will more then likely develop an indirect inguinal hernia through the opening at some point. Some of the cases may result in a hydrocele.
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