SDF‐1 Attenuates Oocyte Quality Decline During Reproductive Aging Through Autophagy‐Enhanced Stress Granule Scavenging

The age-related decline in oocyte quality constitutes a major cause of reduced female fertility. In this study, we investigated the potential of stromal cell-derived factor-1 (SDF-1) to counteract oocyte deterioration during reproductive aging. We observed a significant negative correlation between SDF-1 levels and aging in both human follicular fluid/oocytes and murine ovarian tissues. Utilizing aged mouse models, we found that SDF-1 supplementation, both in vitro and in vivo, was associated with the amelioration of multiple aging-associated oocyte defects, including restored meiotic spindle morphology, improved chromosomal alignment, normalized distribution of cortical granules and mitochondria, enhanced mitochondrial membrane potential, and reduced oxidative stress. Consequently, SDF-1 treatment improved fertilization competence, embryonic developmental potential, and fertility restoration in aged female mice. Mechanistically, transcriptomic and functional analyses suggested that SDF-1 ameliorates oocyte aging primarily by enhancing autophagic activity, which was associated with clearance of accumulated stress granules and mitigation of oxidative damage. Pharmacological inhibition of autophagy attenuated the beneficial effects of SDF-1. In conclusion, our findings point to a previously underexplored role for SDF-1 in alleviating age-related oocyte decline, potentially through autophagy-enhanced stress granule scavenging, positioning SDF-1 as a promising candidate for therapeutic intervention in reproductive aging, although further investigations are warranted in the future.