The urogenital systems:
The urinary system: (the kidney systems)
	These are three systems developing from the intermediate layer of the mesoderm, from anterior to posterior these systems are:
1.the pronephros:
	This is the most anterior system, its excretory units (called the nephrotomes) occurs and disappears in a craniocaudal sequences at the cervical region during the fourth week. 
2.the mesonephros:
	This system develops at the levels of T1-L3 embryonic segments during the fourth week. The excretory tubules (the nephrotomes) lengthen to form S-shaped loop, its medial end forms Bowman’s capsule that acquires glomerular capillaries from the dorsal aorta and thus forming the renal corpuscle or called excretory unit. The lateral end of excretory tubules joins a longitudinal collecting duct called the wolffian mesonephric duct that is connected caudally with the cloaca. The mesonephros disappears at end of the second month, however; few of the caudal tubules and ducts share in formation of the male genital system. 
The mesonephros and the genital ridge (medial to it) will form the urogenital ridge on the sides of the mid-line of the posterior abdominal wall.
3.the metanephros (the definitive kidney):
	It develops caudal to the mesonephros at the fifth week. Its excretory tubules (nephrotomes) form renal corpuscles in the same manner as the mesonephros, the collecting mesonephric duct is replaced by the ureteric bud. 
The ureteric bud projects from the mesonephric duct (near its cloacal end); the bud penetrates the metanephros and dilated to form the renal pelvis, which divides to form the major calyces. Each calyx subdivides till the end of the 5th month, the 2nd, 3rd, and 4th subdivisions fused together to form the minor calyces. The more distal subdivisions will form the collecting tubules of the pyramids at the renal medulla. The ureteric bud below the renal pelvis will form the ureter.          
	The most distal subdivision of the collecting tubules is covered by metanephric tissue cap; the collecting tubules induce this cap to form the renal vesicle that elongate to form the S-shaped excretory tubule. This excretory tubule forming the excretory unites called the nephrons (including; the proximal and distal convoluted tubules and the loop of Henle) that are connecting distally with the adjacent collecting tubules.     
	
Function of the kidney:
	Although the definitive kidney becomes functional near 12th week, urine production begins after formation of the glomeruli at the 10th week. The urine passes into the amniotic fluid and is swallowed by the fetus to be recycled in the kidneys as the excretion is a function of the placental not the kidney.
Anatomy of the developing kidneys:
The excretory units of the nephrons are continuously developed till birth to be about 1 million in number. The postnatal growths in size (not number) of the nephrons contribute to the disappearance of the fetal lobulation of the kidneys. 
The kidneys develop in the pelvis, however; the growth of the lumber and sacral regions and the diminution of the body curvature causes ascend of the kidneys up to pass in between the arterial fork of the umbilical arteries. The kidneys are vascularized, as they ascend, by new branches from the aorta at higher level while the lower vascular branches degenerate.
Clinical correlates:
1. Wilm’s tumor; a cancer of the child kidney due to gene mutation.
2. Renal agenesis or dysplasia; occurs due failure of induction by the ureteric bud to the metanephros either unilateral or bilateral. 
3. Congenital polycystic kidney; either an autosomal recessive or dominant types. It occurs due to obstruction in the urine path from the nephrons to the collecting tubules.
4. Duplication of ureter; due to early splitting of the ureteric bud.
5. Ectopic ureteric opening; rarely one of the ureters opened into the vagina, urethra, or the vestibules.
6. Pelvic kidneys; occurring due to failure of the ascending kidney. 
7.horseshoe kidney; occurring by fusion of the lower poles of the kidneys as the poles are pushed close together during the passage of the kidneys through the fork of the umbilical arteries. The ascending horseshoe kidney stops at the root of the IMA at L3. The ureters pass anterior to the isthmus of this kidney.
8. Accessory renal arteries; occurring due to failure of degeneration of the embryonic arteries during ascend of the kidneys.

The urinary bladder and urethra:
	During the 3-7 weeks a mesodermal layer called the urorectal septum divides the cloaca into: 
1. Primitive anal canal posteriorly.
2. Urogenital sinus anteriorly; this sinus is formed of three parts:
a. the large upper part forming the urinary bladder and is connected with the allantois (the allantois is obliterated later on forming fibrous cord between the bladder and the umbilicus called the urachus or called the median umbilical ligament). The mesonephric ducts are opened into this part of the cloaca, the caudal part of the mesonephric duct is absorbed in the wall of the bladder to form the trigon of the bladder. As a result of this change, the ureteric buds originating from the mesonephric ducts became connected with the trigon of the bladder. Then after, the openings of the mesonephric ducts move together and become connected to the prostatic urethra forming the male ejaculatory ducts (beyond the out-budding of the seminal vesicles). The trigon acquires a transient mesodermal lining from the mesonephric tissue which is replaced later on by the endodermal lining, the same of the whole bladder.   

b. the narrow pelvic part of the urogenital sinus; that will form the prostatic and membranous urethra of male and the its counter-part in female. The lining of the urethra is of endodermal origin, while the connective tissue and muscles surrounding it are derived from its surrounding splanchnic mesoderm.
	At the end of the 3rd month the prostatic urethra shows many budding forming the male prostate. In female, budding from the cranial part of the urethra forms the urethral and Para urethral glands. 
c. the flattened phallic part. 

Clinical correlates:
1. Urachal fistula: it occurs due to failure of the obliteration of the urachus. The urine will out flow from the umbilicus. Partial failure will results in urachal cyst or urachal sinus.
2. Exstrophy of the bladder.
3. Cloacal Exstrophy

Note:
The tip of the urorectal septum will form the perineal body.
The gonads:
A.the indifferent gonad:
The primitive gonadal ridges are formed as proliferating epithelium and as  condensed mesenchyme at the medial side of the urogenital ridges. The epithelia of the urogenital ridge penetrate the underlying mesenchyme forming the primitive sex cords. The primordial germ cells are formed among the dorsal wall of the endoderm of yolk sac close to the allantois during the 3rd week, they migrate by amoeboid movement along the dorsal mesentery of the hind gut to reach the gonads at the 5th week and invading the gonads in the 6th week. The germ cells induce the development and differentiation of the gonads.

B.differentiated gonads:
The male testes:
The primitive sex cords proliferate further to form the testis cords or called the medullary cords. These medullary cords anastomose at the hilum of the testis to form the rete testis. In the 4th month, these cords contain primitive germ cells and sustentacular cells of Sertoli that are derived from the surface epithelium of the genital ridge. The mesoderm of the ridge give rise to the interstitial cells of leydig lying in between the cords and produce testosterone at the 8th week. The testis cords (the medullary cords) are canalized at puberty forming the seminiferous tubules. The fibrous of the tunica albuginea will be formed in-between the these testis cords and the surface epithelium of the gonads.

The ovary:
	The primitive sex cords will be dissociated forming irregular cell clusters, each of these contains the primitive germ cells, and the clusters then are replaced by the vascular stroma of the ovarian medulla. 
	In the 7th week, the epithelium of the female genital ridge will proliferates forming the second cords or called cortical cords near the surface. In the forth month, these cords dissociated also into cell clusters forming the follicular cells of the ovarian cortex that surround the oogonia derived from the germ cells.
Genital ducts:
A. indifferent stage:
Initially the embryos have two pairs of ducts lateral to the genital ridge; the mesonephric and paramesonephric ducts.   The paramesonephric ducts arises as invaginations of the epithelium, cranially they are opened to the abdominal cavity while caudally they run lateral to the mesonephric ducts then crosses ventrally to be medial to it. In the midline the RT and LT paramesonephric ducts fused to form the uterine canal that projects caudally into the wall of the urogenital sinus producing the paramesonephric or Mullerian tubercle. The opening of the mesonephric duct lies on the sides of the Mullerian tubercle.  
  
B. differentiated genital ducts: 
Male genital ducts: 
The caudal excretory tubules of the mesonephros will not disappear forming the vas efferent (from epigenital tubules) connecting the rete testes and vas deferens. Also these tubules will form the vestiges of the paradidymis (from the paragenital tubules). 
The most cranial part of the mesonephric ducts degenerate forming the vestiges of the appendix epididymis. Remaining part of the mesonephric duct form the duct of the epididymis, the vas deferens, and the ejaculatory ducts. The seminal vesicles out bud from the mesonephric ducts at the distal end of the vas deferens. 	
The paramesonephric ducts degenerate forming at their cranial ends the vestiges of the appendix testis.    

Female genital ducts:
	These ducts are derived from the Rt and Lt paramesonephric ducts which have three parts from cranial to caudal; vertical, and horizontal parts forming the uterine tubes, and a caudal vertical parts that are fused at the mid-region forming the uterus.
	At the point of the paramesonephric tubercle, two sinovaginal bulbs grow from the pelvic part of the urogenital sinus to form the vaginal plate. This plate is increased in size and canalized in the 5th month forming the vagina. The upper part of the vagina near the uterus (the fornix of the vagina) is derived from uterine canal derived from the paramesonephric ducts. The phallic part of the urogenital cavity is separated from the vaginal cavity by the hymen which consists of the epithelial lining of the urogenital sinus and a thin layer of vaginal cells.
	Remnant of the cranial and caudal mesonephric excretory tubules may form the vestiges of the epoophoron and paroophoron respectively inside the mesoovarium.  Remnant of the cranial mesonephric duct seen in the epoophoron,and of caudal duct seen the wall of the vagina or the uterus as Gartner’ cyst.  

Clinical correlates:
1.duplication of the uterus: it may result from abnormality in the fusion of the paramesonephric ducts at the uterine canal. This anomalies may be of many types:
a. complete (uterus didelphys) with double vagina. 
b. indented uterus (uterus arcuatus). 
c. two uterine horns and one vagina (uterus bicornis).
d. atresia of the paramesonephric ducts resulting in uterus bicornis with a rudimentary horn, or atresia of the uterine cervix. 
e. abnormal sinuvaginal bulb that may result in double vagina or atresia of the vagina.

Development of the external genitalia:
A.the indifferent stage:
The external genitalia develops during the 3rd to the 6th weeks of gestation. The cloacal membrane is surrounded by bilateral mesodermal cloacal folds. These folds are fused anteriorly forming the genital tubercle. Caudally, these folds are subdivided into two parts; 
1.the urethral folds anteriorly, that surround the urogenital groove.
2.the anal folds posteriorly.
In the same time, the urethral folds become surrounded by the bilateral genital swellings that are the primordial of the scrotum of the male and the labia majora of the female.

B.the differentiated external genitalia:
The external genitalia of the male:
The genital tubercle will be elongated forming the phallus. The phallus is the primordium of the penis and the glans penis. The urethral folds elongate forming the urogenital groove (the urethral groove) that lies on the caudal side of the phallus.. this groove is lined by the endoderm of the urethral plate. The urethral folds will be closed to form the penile urethra at the end of the 3rd month. This part of the urethra never reaches the tip of the phallus, therefore, the ectoderm at the tip of the phallus invaginates to form a cord of tissue between the phallus and the penile urethra, canalization of this cord will form the external urethral meatus. All these developmental changes occurs by the effect of the androgenic testosterone hormone secreted by the testes.
Clinical correlates:
1.hypospadias: occurring by failure of closure of the urethral folds (called also scrotal folds). It causes abnormal urethral opening at the inferior aspect of the penis. Massive failure will results in separation of the scrotal swellings that may simulate the labia majora.
2.apispadias: occurs if the genital tubercle is formed at the caudal end of the cloacal membrane (instead of the normal cranial position). It is associated with abnormal urethral opening at the dorsum of the penis.
3.extrophy of the bladder: failure of mesodermal migration at the primitive streak toward the cloacal membrane. It may be associated with epispadias.
4.micropenis. 5.bifid penis (double penis). 
The external genitalia of the female:
The short genital tubercles will form the clitoris, the unfused urethral folds form the labia minora. The urogenital groove forms the vestibule of the vagina.

Note:
Ultrasonic examination of the fetus during the 3rd and 4th months may lead to wrong diagnosis of the male sex, because in this stage the female has a larger genital tubercle.
Clinical correlate:
Defects in the sexual differentiation of the external genitalia could be seen in:
1.Klinefelter syndrome; karyo type 47 XXY.
2.gonadal dysgenesis; abnormality in the SRY gene.
3.pseudohermophroditis; occurring in males or in females.
4.testicular feminization; occurring due to insensitivity to androgens.

Descend of the testes:
	The gonads are attached to the posterior abdominal wall by the urogenital mesentery, the caudal part of this mesentery is called the caudal genital ligaments. The gubernaculums is a mesenchymal condensation extending between the caudal poles of the testes to the scrotal swellings outside the abdominal cavity. This gubernaculums grows outside the abdomen and thus pulling the testes down, this pulling is assisted by the increased intra-abdominal pressure occur by the growth of the abdominal viscera. Later on, the extra-abdominal part of the gubernaculums regresses and thus completing the passage of the testes through-out the inguinal canal down toward the scrotum. The peritoneal evagination surround the descending testes and forms the processus vaginalis and the tunica vaginalis. The descending testes are also covered by the internal spermatic fascia, the cremasteric fascia, and the external spermatic fascia. These three fascial layers are derived from the muscles of the anterior abdominal wall. The above developmental  changes occurs under the effect of the androgen hormones.

Clinical correlate:
Congenital inguinal hernia:
1.	the intestinal loop may herniated and descend into the scrotum if the processus vaginalis is not normally obliterated at the first year of life. Partial closure of the processus vaginalis will lead to descend of fluid from the peritoneal cavity into the scrotum resulting in hydrocele of the scrotum or the spermatic cord.  
2.	cryptorchism: the testes may remain in the pelvic cavity or inside the inguinal canal.

Descend of the ovary:
This descend occurs in a les degree than the descend of the testes. The ovary reaches just below the pelvic brim. The cranial part of the urogenital mesentery forms the genital ligament that develop to form the suspensory ligament of the ovary. The caudal part of the mesentery forms the caudal genital ligament that forms the ligament of the ovary and the round ligament of the uterus.   

Molecular regulation of the gonads and gnital ducts:
	Sex differentiation may involve many genes, some of them are autosomal. The Y-sex chromosome contain SRY (the sex region of the Y-chromosome, on it short arm), this SRY region produces the testes- determining protein factors that leads to the development of the male criteria. This factor is a transcription factor that leads to expression of the genes responsible for the production of the Mullerian inhibitory substance (MIS = antiMullerian hormones AMH) produced by the Sertoli cells and causes regression of the paramesonephric ducts. Also there will be production of testosterone from the Leydig cells. 
And the vice versa for the female =with estrogen secretion.