Regulation of Ovary Function in Aged Mice by Reactive Oygen Species through the PI3K/Akt/mTOR Pathway

Abstract

In this study, we aimed to explore the effect and underlying mechanism of aging in female ovarian function in mice. The mice at the age of 10 months and 7 weeks were used as the aged model and the young control. The estrus cycle and serum peripheral blood and the number of follicles, oocytes and litter size were also calculated for analysis of ovarian function. Ovarian cells were collected for reactive oxygen species (ROS) and Annexin V staining. Antioxidant and apoptotic proteins BAX and Caspase-3 and phosphoinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in ovaries were also detected. The results showed that compared to the young control, the aged mice exhibited ovarian dysfunction with disrupted estrus cycle and hormone production, accompanied by decreases in the numbers of follicles, oocytes and litter size. The oxidative damage in aged ovarian tissues was induced with increased Malondialdehyde content and reduced activities of Catalase and Superoxide Dismutase enzymes, as well as high level of ROS accumulation and apoptosis in ovarian cells. Furthermore, the expression levels of BAX, Caspase-3 and PI3K, Akt, mTOR and their phosphorylated forms were obviously regulated in the aged ovaries. Thus, these results above suggest oxidative damage with high level of ROS is obviously induced in ovarian tissues of aged mice, and this accumulation mediates apoptosis of ovarian cells, involving with improved expression of apoptotic protein BAX and Caspase-3, ultimately leads to ovarian dysfunction through the PI3K/Akt/mTOR pathway.