Melatonin protects premature ovarian insufficiency induced by tripterygium glycosides: role of SIRT1

Melatonin confers protective effects on premature ovarian insufficiency (POI) induced by tripterygium glycosides (TG) by reducing oxidative stress. Silent information regulator 1 (SIRT1) signaling is found to be associated with the physiology and pathology of ovary. We hypothesize that melatonin could protect POI via activating SIRT1 signaling. The aim of this study was to investigate the protective effect of melatonin on POI and elucidate its potential mechanisms. Mice were assigned to melatonin treatment with or without SIRT1 inhibitor Ex527 or melatonin receptor antagonist luzindole (Luz) and then subjected to POI. Melatonin conferred a protective effect by improving estrous phase, ovarian and uterus mass and index, increasing ovarian follicles, corpus luteum and anti-mullerian hormone (AMH), decreasing atresia follicles and follicle stimulating hormone (FSH). Melatonin treatment also could reduce malondialdehyde (MDA) level, MDA5, Gp91^phox, Caspase3 and Bax expression, and increase total antioxidant activity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and Bcl-2 expression by up-regulating SIRT1 signaling. However, these protective effects were blocked by Ex527 and Luz, indicating that SIRT1 signaling and melatonin receptor might be specially involved in these effects. In summary, these findings suggest that melatonin protects POI by reducing oxidative stress and apoptotic damage via activation of SIRT1 signaling in a receptor-dependent manner.