Salidroside alleviates age-related metaphase II oocyte aging by enhancing mitochondrial complex I-mediated oxidative phosphorylation

The deterioration of metaphase II (MII) oocyte quality is a principal factor compromising fertility in women of advanced maternal age and a core hallmark of ovarian aging; however, effective interventions to counteract this age-related decline are currently lacking. Although salidroside (Sal) exhibits health-promoting and anti-aging properties, its protective effects against MII oocyte aging and the underlying mechanisms remain poorly understood. In this study, we demonstrated that salidroside supplementation significantly improved multiple aspects of MII oocyte quality, particularly oocyte maturation and developmental competence. Comprehensive transcriptomic analysis revealed that salidroside rescues aged oocyte quality primarily by enhancing oxidative phosphorylation (OXPHOS). This enhancement effectively reduced reactive oxygen species (ROS) accumulation, thereby attenuating DNA damage and apoptosis. Furthermore, we identified that differentially expressed genes in the OXPHOS pathway were predominantly enriched in the subunits of mitochondrial respiratory chain complex I. The protective effects of salidroside in aged MII oocytes were markedly abolished by rotenone, indicating that salidroside primarily exerts its beneficial effects through mitochondrial complex I-mediated OXPHOS. Together, our findings highlight salidroside supplementation as a promising therapeutic strategy to ameliorate age-related MII oocyte deterioration, delay ovarian aging and improve reproductive outcomes. Future studies should focus on the translational potential of this intervention for human clinical applications.