The Bile Acid Nuclear Receptor FXRα Is a Critical Regulator of Mouse Germ Cell Fate

Spermatogenesis is the process by which spermatozoa are generated from spermatogonia. This cell population is heterogeneous, with self-renewing spermatogonial stem cells (SSCs) and progenitor spermatogonia that will continue on a path of differentiation. Only SSCs have the ability to regenerate and sustain spermatogenesis. This makes the testis a good model to investigate stem cell biology. The Farnesoid X Receptor alpha (FXRα) was recently shown to be expressed in the testis. However, its global impact on germ cell homeostasis has not yet been studied. Here, using a phenotyping approach in Fxrα−/− mice, we describe unexpected roles of FXRα on germ cell physiology independent of its effects on somatic cells. FXRα helps establish and maintain an undifferentiated germ cell pool and in turn influences male fertility. FXRα regulates the expression of several pluripotency factors. Among these, in vitro approaches show that FXRα controls the expression of the pluripotency marker Lin28 in the germ cells. [Display omitted] •FXRα regulated germ cell apoptotis independently of androgen homeostasis•FXRα controls germ cell differentiation•FXRα regulates the establishment and maintenance of undifferentiated germ cells•In germ cells, FXRα controls the expression of pluripotency markers such as Lin28 Martinot et al. report that FXRα controls the fate of undifferentiated spermatogonia.