Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders

Several studies have reported an association between the farnesoid X receptor alpha (FXR alpha) and estrogenic signaling pathways. Fxr alpha could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXR alpha antagonist. Following the exposure to both molecules, wild-type animals showed impaired fertility and lower sperm cell production associated with the alteration of the establishment and maintenance of the undifferentiated germ cell pool. The crosstalk between BPA and FXR alpha is further supported by the lower impact of BPA in mice genetically ablated for Fxr alpha and the fact that BPA counteracted the effects of FXR alpha agonists. These effects might result from the downregulation of Fxr alpha expression following BPA exposure. BPA and S act additively in human testis. Our data demonstrate that FXR alpha activity modulates the impact of BPA on male gonads and on undifferentiated germ cell population.