[Gly14]-humanin exerts a protective effect against D-galactose-induced primary ovarian insufficiency in mice

Research Question : In this study, we aimed to investigate the protective effect of the humanin derivative [Gly14]-humanin (HNG) on a D-gal-induced mouse model of POI and its underlying mechanism. Design : D-gal (200mg/kg/d) was injected subcutaneously for 6 weeks to induce the mouse POI model, and the HNG treated mice were injected intraperitoneally with different concentrations of HNG for 6 weeks. Ovarian morphology, function, levels of sex hormones as well as the states of oxidative stress in the ovary and throughout the body were evaluated. Results : Compared with the D-gal group, HNG improved the abnormal ovarian morphology and estrous cycle, increased the number of ovarian follicles and litters, as well as the levels of estrogen and anti-Müllerian hormone (AMH). After HNG administration, antioxidant indicators, including the total antioxidant capacity (T-AOC), catalase (CAT), and glutathione (GSH) in the ovaries and serum of mice were significantly increased, while the oxidation indicator malondialdehyde (MDA) decreased significantly. In addition, exogenous injection of HNG significantly reduced apoptosis of ovarian granulosa cells and reduced the expression levels of senescence-related proteins p53, p21 and p16. The level of autophagy in ovarian tissue of HNG-treated mice increased significantly while the level of p62 protein was significantly reduced and the level of LC3 protein was significantly increased. Conclusions : This study showed that HNG was able to inhibit D-gal-induced oxidative stress, apoptosis, and ovarian damage, promoting ovarian autophagy, suggesting that HNG may be a potential prophylactic agent against POI.