Trehalose Alleviates D-Galactose-Induced Aging-Related Granulosa Cell Death in Ovaries

Ovarian dysfunction caused by aging restricts female reproductive capacity and is accompanied by oxidative stress and impaired autophagy. Recent studies have shown that trehalose (Tre) can activate autophagy and have antioxidant effects. However, whether Tre can be used to attenuate ovarian aging remains unclear. Therefore, the anti-aging effects of Tre on the ovary were explored both in vivo and in vitro. D-galactose (D-gal) was administered i.p. daily (200 mg/kg body weight) for 8 weeks to establish the mouse ovarian aging model (n = 10). We found that Tre significantly reversed ovarian weight loss and reduced the number of TUNEL-positive granulosa cells caused by D-gal in mouse ovaries. Tre elevated the protein expression levels of LC3-II, Parkin, PINK1, Beclin1, and LAMP2 in ovaries. Mitochondrial-related proteins TOM20 and COX IV expression levels were increased by Tre administration. In vitro studies further supported these findings, showing that Tre treatment significantly reduced the number of SA-beta-gal and PI-positive cells, and decreased ROS levels in cultured granulosa cells. Thus, Tre alleviates ovarian aging by activating mitophagy and reducing oxidative stress, suggesting its potential as an anti-aging agent for ovarian health.