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

ABSTRACT: Several studies have reported an association between the farnesoid X receptor alpha (FXR?) and estrogenic signaling pathways. Fxr? 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? 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? is further supported by the lower impact of BPA in mice genetically ablated for Fxr? and the fact that BPA counteracted the effects of FXR? agonists. These effects might result from the downregulation of Fxr? expression following BPA exposure. BPA and S act additively in human testis. Our data demonstrate that FXR? activity modulates the impact of BPA on male gonads and on undifferentiated germ cell population.

SUBMITTER: Sedes L 

PROVIDER: S-EPMC6178796 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature