THE FACTORS OF SEXUAL DIFFERENTIATION During the development of the urogenital system, the morphological transformationsdescribed above take place in several stages controlled by factors which intervenesuccessively. Normal development requires the harmonious intervention of this “cascade offactors” on all the constituents of the urogenital system. 1. Chromosomal determinism The first determining step occurs at the time of fertilization according to the sex chromosomeof the fertilizing sperm. If it is a Y chromosome, the zygote will have the chromosomalformula 46 XY and differentiation will take place towards masculinization. If it is an Xchromosome, the zygote will have the chromosomal formula 46 XX; in the absence of a Ychromosome, differentiation will move towards feminization. 2. Testicular differentiation factor This factor, called TDF (testis determining factor), is a protein encoded by an SRY genelocated on the short arm of the Y chromosome which is expressed in the cells of the wall ofthe sexual cords and induces their organization into testicular cords. Other genes could beinvolved, in particular the SOX 9 gene. 3. Hormonal factors Hormonal factors will directly or indirectly induce other transformations of the genital system. In the male sex At the level of the fetal testicle, the Sertoli cells secrete a antiMüllerian hormone (AMH)which will cause the regression of the Müllerian ducts from the 8th week, they also have aninducing role for the development of Leydig cells of the interstitial tissue. Leydig cells, upontheir individualization, secrete testosterone. During differentiation this hormone induces the development of Wolffian ducts and theirderivatives, later during fetal life they induce the masculinization of organs which presentsexual dimorphism and, at puberty, the organization of the tubes seminiferous and thetriggering of spermatogenesis. At the level of the derivatives of the wall of the urogenital sinus and the external genitalorgans, masculinization (formation of the prostate and bulbourethral glands) also depends
on the presence of male hormone but the tissue receptors are only stimulated by thepresence a reduced form of testosterone, dihydrotestosterone (DHT). This reductionrequires the presence of an enzyme, 5α reductase. In the female sex In the absence of TDF, the undifferentiated gonad transforms into a fetal ovary: the sexcords fragment and during fetal life, the cells are organized into follicles around the germcells which become oogonia (meioses are triggered at from the 5th month). In the absenceof anti-Müllerian hormone, paramesonephrotic ducts develop into the tubes and theuterovaginal canal. In the absence of testosterone, the Wolffian ducts regress, the posteriorwall of the urogenital sinus gives rise to the vaginal plate and the external genitalia changelittle.