PHB2 binds to ERß to induce the autophagy of porcine ovarian granulosa cells through mTOR phosphorylation.

Autophagy of ovarian granulosa cells is one of the reasons which results in follicular atresia. PHB2 regulates many fundamental biological processes and is pivotal in the mitophagy of cells; nevertheless, the autophagy in the porcine ovary and how PHB2 regulates the follicular cells are unknown. Here we report a protein complex that induces autophagy in porcine granulosa cells (PGCs) through the direct interaction of ERß and PHB2. In this study, we aimed to elucidate the autophagy and the role of PHB2 in porcine ovaries using porcine primary ovarian granulosa cells (PGCs). The results showed that PHB2 induces PGCs autophagy because of the change in related genes and protein expression levels. In addition, the results of Co-IP and the distribution of the combination of PHB2 and ERß showed that this complex is also indicated as an essential role of PHB2 in PGCs autophagy. Based on our results, it can be concluded that PHB2 combined with ERß induces PGCs autophagy by targeting the mTOR pathway. This study pinpoints a novel regulatory mechanism of autophagy and demonstrates the existence of a protein complex that may underlie its roles in autophagy in PGCs.

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERß-induced autophagy.

It is well known that approximately 99% of ovarian follicles in mammals suffer from a degenerative process known as atresia, which is a huge waste of genetic resource in female animals. Studies have shown that activin A (ACT-A) is located in ovarian granulosa cells and has different effects in granulosa cell depending on species. Although granulosa cells play a critical role during follicular atresia, the mechanism of action of ACT-A in bovine ovarian granulosa cells (BGC) is poorly understood. In this study, we first determined the apoptosis of BGCs isolated from growth follicles and atretic follicles respectively. Then, BGC isolated from atretic follicles were used as a model to elucidate the role of ACT-A in cattle ovary. The results showed that apoptosis occurred in both growing follicles and atretic follicles, and the percentage of apoptotic cells in atretic follicles was higher than that in growing follicles. The current results indicated that ACT-A can attenuate apoptosis of BGC by maintaining the function of BGC in atretic follicles. Increased ERß induced by ACT-A promoted BGC autophagy but had no effect on apoptosis. In summary, this study suggests that ACT-A attenuates BGC apoptosis in atretic follicles by ERß-mediated autophagy signalling.