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Embryology of the genital tract

The development of the genital system includes three parts:
The gonads.
The genital ducts.
The external genetalia.
Each has different developmental origin.
The Y-chromosome always directs the developing gonads into testis via its testis-determining factor (TDF) gene allocated in the testis determining region (SRY).

Development of the genital organs:

Both the genital organs and urinary tract develop from the intermediate cell mass mesoderm. The pronephros and mesonephros develop to form the primitive kidney but disappears subsequently and finally the metanephros appears to form the definitive kidney. The duct of the pronephros and mesonephros persist as the Wolfian duct, which runs caudally to join the urogenital sinus. On the medial aspect of the mesonephros, the genital ridge appears as a swelling in which a gonad is to be developed. On the lateral side of the mesonephros develops the Mullerian duct from which the female genital tract develops.

Differentiation of the gonad:

Gonads appear as a pair of longitudinal ridges called: the genital ridges formed from proliferation of the coelomic epithelium and condensation of underlying mesenchyme over the ventral surface of the mesonephros. The primordial germ cells appear among the endodermal cells in the wall of yolk sac, they migrate by amoeboid movement along the dorsal mesentery of the hindgut reaching the genital ridge by the beginning of the 5th week. If there is no Y-chromosome, the primitive gonads start to become ovaries.

Indifferent stage (in both sexes):

The coelomic epithelium of the ridge proliferates and the epithelial cells penetrate the underlying mesoderm forming number of irregular cords called primitive sex cords, in both sexes these cords are connected to the surface epithelium and not possible to differentiate between both sexes.

Differentiation stage:

Testis:
In genetically male embryo (Y-chromosome), at 7 weeks the primitive sex cords continue to proliferate and penetrate deep into the medulla to form medullary cords. Toward the hilum of the gonad the cords break into network of tiny cell strands giving rise of rete testis and they loose contact with the surface epithelium, the cords are composed of primitive germ cells and the sustentacular cells of Sertoli that are derived from the surface epithelium, while Leydig cells derived from the underlying mesenchyme and they lie between the cords.
By 8weeks these cells begin to produce testosterone, which in turn influences the development of the genital ducts and the external genetalia. Medullary cords form seminiferous tubules when acquire a lumen at puberty.


Differentiation stage:
Ovary:
In female embryo no Y-chromosome, the primitive sex cords dissociate into cell clusters around the primitive germ cells, they are located in the deep ovarian medulla, soon they disappear and replaced by vascular stoma of ovarian medulla. Unlike the testis, in the 7th week, the surface epithelium gives rises to a second generation of cords called: cortical cords, because they remain close to the surface. In the 4th month these cords split into cell clusters around one or more of the primitive germ cells. The germ cells then develop into oogonia while the surrounding epithelium that descend from the surface form follicular cells.

Development of genital duct:
Indifferent stage:
Both sexes have two pairs of ducts, mesonephric and paramesonephric ducts. The first one forms the future ureter and male genital ducts while the second one form the female genital ducts.
The paramesonephric ducts (Mullerian) arise at 5-6 weeks as a longitudinal invagination by ingrowth of the coelomic epithelium on the antero-lateral surface of the urogenital ridge. Cranially, the duct opens into the coelomic cavity with a funnel-shaped structure and caudally it first runs lateral to mesonephric duct but then cross it ventrally , in the midline it comes in close contact with the duct of the opposite site then fuse to form the uterine canal . The caudal tip of the fused canals projects into the posterior wall of the urogenital sinus where it causes a small swelling called the Mullerian tubercle. The mesonephric duct opens into the urogenital sinus on either sides of the Mullerian tubercle.
Note: Cloaca divides into the urogenital sinus (form future bladder and lower vagina), rectum and anal canal.

Differentiation stage:

In the absence of functioning testis, the Mullerian system develops into the fallopian tubes, uterus and vagina. The Wolfian ducts begin to degenerate and subsequently disappear.
The development of the genital ducts and external genetalia are under the influence of hormones circulating in the fetus. In male fetus, Sertoli cells of the fetal testis produce a non-steroidal substance: Mullerian inhibiting substance (MIS) or antiMullerian hormone causing regression of the duct. Fetal testis produces also testosterone, which promotes the development of mesonephric duct and virilizes the external genetalia. So in male fetus under the hormones mentioned above, The Mullerian duct regress and the mesonephric duct (Wolfian) will develop into ductus deference, ejaculatory duct. While in the female fetus because of the lack of these hormones, the Mullerian duct will develop into main genital ducts:
Cranial vertical portion opens into coelomic cavity.
Horizontal part that cross the mesonephric duct.
Caudal vertical part that fuses with the opposite partner.
The first two parts develop into fallopian tube and the fused part form uterine canal and the upper vagina.

Development of the vagina:

After the caudal tip of the paramesonephric ducts has reached the urogenital sinus, two solid evaginations grow out from the sinus, they are called: sino-vaginal bulbs. They proliferate to form a solid vaginal plate which proliferates cranially increasing the distance between the uterus and the urogenital sinus. By the 5th month the vagina is completely canalized.
The vagina has a double origin: most of the upper vaginal portions (fornices) are Mullerian in origin while the lower portion derived from the urogenital sinus. The lumen of the vagina remain separated from that of the urogenital by a thin tissue layer called: hymen


Development of external genetalia:
Indifferent stage:
In the 3rd week of development, mesenchymal cells originating in the region of primitive streak migrate around the cloacal membrane on the external aspect of the urogenital sinus anteriorly to form a pair of slightly elevated folds called: cloacal folds. Cranially the folds unite to form the genital tubercle.
In the 6th week the cloacal membrane divide into urogenital and anal membrane, same the cloacal folds are subdivided into urethral folds anteriorly and anal fold posteriorly. At the same time a pair of elevations called the genital swellings become visible on each side of the urethral folds these swellings later form the scrotal swelling in the male and the labia majora in the female.
At the end of the 6th week it is impossible to distinguish between the two sexes.

Differential stage:

Male fetus:
Under the influence of androgens secreted by fetal testis, the external genetalia develop with rapid elongation of the genital tubercle to form the phallus. The phallus forms the shaft of the penis and glans; the genital swelling will form the scrotum. The phallus pulls the urethral folds forward which then fuse to from penile urethra.

Differential stage:

Female fetus:
In the absence of androgens and presence of estrogen, the genital tubercle elongate only slightly to form the clitoris, the urethral folds do not fuse but develop into labia minora. The genital swellings enlarge to form labia majora.










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رفعت المحاضرة من قبل: Mostafa Altae
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