FSH-inhibited autophagy protects against oxidative stress in goat Sertoli cells through p62-Nrf2 pathway.

Oxidative stress is a common cause of male infertility. Sertoli cells are one of the target cells of oxidative injury, which leads to impaired testicular function. Follicle-stimulating hormone (FSH) is critical in Sertoli cell function. However, the role of FSH in the response of goat Sertoli cells to HO-induced oxidative stress has not been studied yet. To investigate this response, we established an oxidative stress model using goat Sertoli cells. FSH pretreatment significantly enhanced the decreased cell viability (p < 0.05) caused by oxidative injury and inhibited autophagic flux. FSH significantly increased p62 mRNA and protein levels (p < 0.01). Further investigations revealed that FSH also increased the expression level and nuclear translocation of Nrf2 in Sertoli cells (p < 0.01), which resulted in increased antioxidant enzyme activity (p < 0.05). In contrast, treatment with siNrf2 and sip62 abolished this protective effect of FSH. These findings suggest that FSH protects Sertoli cells against oxidative stress via the p62-Nrf2 pathway, and that p62 accumulation maintains persistent activation of Nrf2. Thus, p62 and Nrf2 are required for FSH-mediated protective role in HO-induced Sertoli cell injury. The findings reveal new mechanisms by which FSH protects against oxidative injury in goat Sertoli cells.