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

Summary Spermatogenesisis 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 Receptoralpha (FXRα) was recently shown to be expressed in the testis. However, its global impact on germ cellhomeostasis has not yet been studied. Here, using a phenotyping approach in Fxrα −/− mice, we describe unexpected roles of FXRα on germ cellphysiology independent of its effects on somatic cells. FXRα helps establish and maintain an undifferentiated germ cellpool 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 Lin28in the germ cells.