Fig. 1.

Impacts of FXRα signaling pathways within the testis. The liver secretes the insulin growth factor-1 and is involved in the control of steroid catabolism; two factors that are known to be key for testicular homeostasis. In addition, DCA produced by the microbiota is an important mediator of BA-induced testicular toxicity. IGF1, BA and LH reach the testis through blood circulation. Testicular BA pool is composed of both circulating ones and those produced within the testis. There, BA will control the Leydig endocrine function by controlling the production of steroid directly or through the decrease of the sensitivity to the LH signaling. In combination, through FXRα or TGR5, BA will control the exocrine function with impact on Sertoli cell homeostasis as well as alterations of processes involved in spermatogonial stem cell (SSC) self-renewal or germ cell survival. In addition, this later impact could also be associated with the increase of BA-precursors and the subsequent activation of CAR signaling pathways. This leads to lower sperm production and then male fertility disorders