Reconstitution of sex determination and the testicular niche using mouse pluripotent stem cells

Abstract

Proper differentiation of gonadal somatic cells is crucial for sex determination and the production of sex hormones and gametes, and reconstituting this process in culture would both deepen our understanding of this process and enable the generation of gametes in vitro. Here, we report the reconstitution of testicular somatic cells using mouse pluripotent stem cells. The reconstitution recapitulated the sex-determination process, yielding cell types that formed seminiferous tubules and adjacent interstitial tissues. The reconstituted testicular tissue incorporated pluripotent stem cell-derived primordial germ cells and supported their differentiation into spermatogonial stem cells. These spermatogonial stem cells differentiated into functional spermatozoa upon transplantation into testis. This study contributes to a deeper understanding of the sex-determination process and to the creation of an alternative source for the male germ line in culture.