Development of gonads and sex differentiation

Development of gonads and sex differentiation
Sex differentiation is a complex process that involves many genes, including some that are autosomal. The key to sexual dimorphism is the Y chromosome, which contains the testis-determining gene called the SRY (sex-determining region on Y) gene on its short arm (Yp11). The protein product of this gene is a transcription factor initiating a cascade of downstream genes that determine the fate of rudimentary sexual organs. The SRY protein is the testis-determining factor. When this transcription factor is expressed in the somatic support cells of the indifferent presumptive gonad, male development is triggered. This step is called primary sex determination. If the factor is absent or defective, female development occurs.

Sex determination and manifestation begins with genetic sex determination (46,XX or 46,XY) that occurs at fertilization. The sexual genotype is responsible for directing gonadal development (testis versus ovary). This in turn directs reproductive tract (internal organs) and external genitalia development.

Gonads
Gonads do not acquire male/female morphological characteristics until the 7th week of development. Gonads appear initially as a pair of longitudinal ridges, genital/gonadal ridges. They are formed by proliferation of the epithelium and a condensation of underlying mesenchyme. Germ cells do not appear in the genital ridges until the 6th week of development.

Primordial germ cells originate in the epiblast, migrate through the primitive streak, and by the 3rd week reside among endoderm cells in the wall of the yolk sac close to the allantois. During the 4th week, they migrate by ameboid movement along the dorsal mesentery of the hindgut. Arrive at the primitive gonads at the beginning of the 5th week and invade the genital ridges in the 6th week. During the 6th week, cells from coelomic epithelium form aggregates of somatic supporting cells that completely invest the germ cells. Somatic support cells are essential for germ cell development within the gonad. If this cells do not invest the germ cells, they will degenerate.

Primordial germ cells have an inductive influence on development of the gonad into ovary or testis. Shortly before and during arrival of primordial germ cells, epithelium of genital ridge proliferates, and epitelial cells penetrate the underlying mesenchyme. They form a number of irregularly shaped cords, primitive sex cords. In both female and male embryos, these cords are connected to surface epithelium. Is impossible to differentiate between male/female gonad. The gonad is known as indifferent gonad. From the 7th week on, male and female systems pursue diverging pathways.

Testis
If the embryo is genetically male, primordial germ cells carry an XY sex chromosome complex. Under influence of the SRY gene on Y chromosome, which encodes the testis-determining factor, primitive sex cords continue to proliferate and penetrate deep into the medulla to form the testis/medullary cords. Toward the hilum of the gland, the cords break up into a network of tiny cell strands that later give rise to tubules of the rete testis. During further development, a dense layer of fibrous connective tissue, the tunica albuginea, separates testis cords from surface epithelium. In the 4th month, testis cords become horseshoe-shaped, and their extremities are continuos with those of the rete testis. Testis cords are now composed of primitive germ cells and sustentacular cells of Sertoli derived form surface epithelium of gland. Interstitial cells of Leydig, derived from the original mesenchyme of the gonadal ridge, lie between the testis cords. By the 8th week, Leydig cells begin production of testosterone and the testis is able to influence sexual differentiation of the genital ducts and external genitalia. Testis cords remain solid until puberty, when they acquire a lumen, thus forming the seminiferous tubules. Once seminiferous tubules are canalized, they join the rete testis tubules, which in turn enter the ductuli efferentes. These efferent ductules are the remaining parts of the excretory tubules of the mesonephric system. They link the rete testis and the mesonephric/wolffian duct, whcih becomes the ductus deferens.

Ovaries
In female embryos (having an XX sex chromosome complement and no Y chromosome), primitive sex cords dissociate into irregular cell clusters. Later, they disappear and are replaced by a vascular stroma that forms the ovarian medulla.

In the 7th week, a new generation of cords is generated, cortical cords, because of the continuing proliferation of the surface epithelium of the female gonad (in male this proliferation does not happen). These cords penetrate the underlying mesenchyme (any loosely organized tissue containing fibroblast-like cells and extracellular matrix regardless of the origin of the cells) but remain close to the surface.

In the third month, these cords split into isolated cell clusters that continue to proliferate and begin to surround each oogonium with a layer of epithelial cells called follicular cells. Together, the oogonia and the follicular cells constitute a primordial follicle.

In embryos with an XX chromosome configuration, medullary cords of the gonads regress and a secondary generation of cortical cords develops. In embryos with an XY sex chromosome complex, medullary cords develop into testis cords and secondary cortical cords fail to develop. Descent of the ovaries is considerably less in the female than in the male, settling just below the rim of the true pelvis. The cranial genital ligament forms the suspensory ligament of the ovary, whereas the caudal genital ligament forms the ligament of the ovary proper and the round ligament of the uterus. The latter extends into the labia majora.