Effects of on steroidogenesis and apoptosis in goat luteinized granulosa cells.

During goat follicular development, abnormal expression of nuclear respiratory factor 1 () in granulosa cells may drive follicular atresia with unknown regulatory mechanisms. In this study, we investigated the effects of on steroidogenesis and cell apoptosis by overexpressing or silencing it in goat luteinized granulosa cells (LGCs). Results showed that knockdown of expression significantly inhibited the expression of and , which are involved in sex steroid hormones synthesis, and led to lower estrogen levels. Knockdown of resulted in an increased percentage of apoptosis, probably due to the release of cytochrome c from mitochondria, accompanied by upregulating mRNA and protein levels of apoptosis-related markers BAX, caspase 3 and caspase 9. These data indicate that might be related with steroidogenesis and cell apoptosis. Furthermore, silence reduced mitochondrial transcription factor A () transcription activity, mtDNA copy number and ATP level. Simultaneously, knockdown of suppressed the transcription and translation levels of SOD, GPx and CAT, decreased glutathione level and increased 8-OHdG level. However, the overexpression of in LGCs or gain of in silenced LGCs increased the expression of genes involved in mitochondrial function and biogenesis, and elevated the antioxidant stress system and steroids synthesis. Taken together, aberrant expression of could induce mitochondrial dysfunction and disturb the cellular redox balance, which lead to disturbance of steroid hormone synthesis, and trigger LGC apoptosis through the mitochondria-dependent pathway. These findings will be helpful for understanding the role of in goat ovarian follicular development and atresia.