Testicular morphogenesis: comparison of in vivo and in vitro models to study male gonadal development

The organogenesis of a functional testis is the basis for male fertility and perpetuation of each species. In mammals, testicular development is dependent on two crucial events during embryonic and pubertal development. First, primary sex determination is initiated by expression of the Sry gene on the Y chromosome and directs the primordial gonad toward testicular development rather than ovarian differentiation. The male pathway comprises highly regulated cell differentiation of somatic cells within the gonadal primordium, as well as migration of mesonephric cells and primordial germ cells, ultimately leading to the formation of testis cords. These cords present the earliest visible sign of male gonadal differentiation. Second, during puberty immature Sertoli cells cease to proliferate and differentiate into their postmitotic, adult phenotype. The maturation of the Sertoli cells is pivotal for initiation and maintenance of spermatogenesis. The regulation of the two separate functions of Sertoli cells-during testis development and in spermatogenesis-are poorly understood. In this review, different models that have been used to study embryonic gonadal development and testicular maturation are compared. In vivo models, organ, and cell culture systems are discussed as regards their applicability to study testicular organogenesis. Then, a new tissue engineering approach is presented that mimics male embryonic gonadogenesis and that offers novel ways to study early testicular differentiation, as well as Sertoli cell maturation and spermatogonial stem-cell niche formation.