Activin A Reduces Porcine Granulosa Cells Apoptosis via ERβ-Dependent ROS Modulation

SIMPLE SUMMARY: Activins and inhibins are closely related protein heterodimers with opposing functions in follicular development. The increased circulating follicle-stimulating hormone (FSH) levels and strengthened estrus behavior may result from the immune neutralization of the inhibin bioactivity, which might improve ovarian follicle formation. However, the direct effect of activins, or immunization against inhibin, on the granulosa cells (GCs) functions remains largely unknown. We aimed to examine the effects of activin A (ACT-A) on the function of porcine ovarian GCs. The results showed that ACT-A could suppress ROS accumulation through the upregulation of the expression of estrogen receptor-β (ERβ), thus attenuating apoptosis in the porcine granulosa cells and promoting estradiol synthesis. These results identified a novel protective role of ACT-A in the regulation of the follicle functions, which revealed the mechanism of improvement locally in the ovary caused by immunization against inhibin. ABSTRACT: Unfavorable conditions compromise animal reproduction by altering the ovarian granulosa cells’ follicular dynamics and normal physiological function (GCs), eventually resulting in oxidative damage and cell apoptosis. Activin is produced in the GCs and plays a vital role in folliculogenesis. This study investigated the effects of activin A (ACT-A) treatment in vitro on the apoptosis of porcine GCs and the underlying molecular mechanism. We found that ACT-A could attenuate the apoptosis of the GCs and enhance the synthesis of estrogen (E2). ACT-A also enhanced FSH-induced estrogen receptor-β (ERβ) expression, inhibiting ERβ aggravated intracellular accumulation of the reactive oxygen species (ROS) and apoptosis. The E2 levels in the culture medium, the mRNA expression pattern of the apoptosis-related genes (CASPASE 3, BCL2, and BAX), steroidogenesis-related gene (CYP19A1), and cell viability were analyzed to confirm the results. In summary, this study indicated the protective role of ACT-A in apoptosis by attenuating the ROS accumulation through ERβ. These results aim to enhance the follicular functions and improve animal reproductive performance.