Human Placental Extracts Improve Ovarian Function by Reducing Follicular Atresia in Mice With CTX-Induced Premature Ovarian Failure

The details of the pathogenic mechanisms underlying premature ovarian failure (POF) remain unknown. Accumulating evidence suggests that primordial follicle inactivity, disorders affecting follicular survival and growth and follicular atresia may affect an individual’s susceptibility to POF. The Rictor/mTORC2/Akt/Foxo3a pathway plays a central role in cytoskeletal construction and follicle survival. As a stronger alkylating agent that exerts immunosuppressive effects, cyclophosphamide (CTX) is widely used in clinical practice, especially in cancer. However, it also has significant reproductive toxicity. CTX accelerates the development of ovarian follicles into mature follicles, resulting in a decreased follicular reserve and ultimately leading to ovarian failure or even POF. We have sought to research effective methods to reduce the damage caused by CTX. Here, we investigated the protective role of human placental extracts on CTX-induced ovarian injury in mice. We describe the effects of HEP on histopathology, the number of atretic follicles, the weight of the ovary, serum hormone levels and apoptosis in granulosa cells. Our data show that ovarian injury can be effectively attenuated by HPE administration. Ovarian weight was higher, the number of atretic follicles was lower, the serum levels of the hormones E2 and P were higher, and the rate of apoptosis and the serum levels of the hormones LH and FSH were lower in granulosa cells in mice treated with HPE for 2 weeks than in the control group. A t the molecular level, our results demonstrated that HPE can be used to inhibit the expression of p-Rictor, Bad, Bax and PPAR and activate the expression of p-Akt and p-Foxo3a, thus preventing follicular granulosa cells from undergoing a higher rate of apoptosis and blocking atresia follicle formation. These effects alleviated CTX-induced ovarian injury by affecting the Rictor/mTORC2/Akt/Foxo3a signalling pathway.