Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


Development of the Bipotential Urogenital (Gonadal) Ridge

An overview of human sex determination and differentiation is depicted in Figures 36-1 and 36-2. The genetic sex of an infant is determined by which paternal sex chromosome, X or Y, was inherited.1,2,3 Sex determination refers to gonad differentiation that culminates with the developmental choice of the bipotential and undifferentiated gonad to become either testis or ovary. Sex differentiation refers to the developmental events that occur after the gonads have differentiated, for instance the formation of the penis or the clitoris.

FIGURE 36-1.

Normal XY sex determination and differentiation. The male sex determination cascade has been elucidated through studies of human mutations and animal genetic models. The presence of SRY initiates the development of the bipotential urogenital ridge toward the formation of Sertoli cells, mature testicular cords, and Leydig cells; CBX2, chromobox 2; GATA4, GATA binding protein 4; NROB1, nuclear receptor family 0 group B member 1; WT-1, Wilms tumor 1; SF-1, steroidogenic factor 1; Lhx9, Lim homeobox 9; Emx2, empty spiracles homolog 2; M33, mouse homolog of chromobox homelog 2; Ir, insulin receptor; Irr, insulin-related receptor: Igf1r, insulin-like growth factor 1 receptor; FOG2, friend of GATA 2; SRY, sex-determining region on Y; SOX9, SRY-like homeobox 9; INSL3, insulin-like growth factor 3; DHH, desert hedgehog; DHT, dihydrotestosterone.

FIGURE 36-2.

Normal XX sex determination and differentiation. Relative to male sex determination, the genetics of the female pathway are less well defined. Absence of SRY and expression of WNT-4 promote typical ovarian vasculature and the organization of oocytes and mesenchymal cells. The absence of testosterone and AMH allows for the development of female external and internal genitalia. WNT-4, wingless-type integration factor 4; Fst, follistatin.

The early stages of sex determination, equivalent in mammals to gonadal determination, begin when primordial germ cells migrate from the yolk sac to the undifferentiated urogenital ridge on the mesonephric bulge between the 6th and 7th weeks of gestation (between 4 and 5 weeks post-fertilization). The differentiation of these cells from the intermediate mesoderm is dependent on the transcriptional activity of several transcription factors whose roles remain poorly understood.

Mouse genetic models have implicated several ubiquitously expressed homeobox genes (Lhx9, Emx2, M33), transcription factors (Sf1, GATA4), and growth factor signaling genes (Ir, Igf1r, Irr, Fgf9) in the development and maintenance of the urogenital ridge,4,5,6 largely by promoting cell proliferation and preventing apoptosis. Studies of human mutations have paralleled some of the mouse data. For instance, the transcription factors Wilms tumor 1 (WT-1) and steroidogenic factor 1 (SF-1) demonstrate high transcriptional activity in the bipotential gonadal ridge prior to gonadal differentiation, and inactivating mutations of the corresponding genes in humans affect the ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.