Reproductive aging is closely associated with poor oocyte quality in vitro maturation, but effective approaches to ameliorate it have still not been fully determined. Here, we found that SS-31 supplementation efficaciously improved oocyte maturation and early embryonic development from aged mice. Specifically, SS-31 remarkably restored the normal spindle/chromosome structure, fertilization ability, mitochondrial distribution, ΔΨm and mitophagy in aged oocytes. In contrast, SS-31 reduced oocyte aneuploidy, ROS accumulation and DNA damage. Mechanistically, single-cell transcriptome analysis reveals that SS-31 increased the maternal mRNA degradation, and the levels of genes associated with mitochondrial function and mitophagy in aged oocytes, such as Pink1, Rps27a, Tomm7 and Map1lc3b. In addition, SS-31 suppressed chromatin organization, histone modification and chromatin remodeling pathways. Moreover, we applied the single-cell untargeted metabolomics to identify that SS-31 increased the levels of spermidine and GSH, which were critical metabolites to protect oocytes against aging. Our data reveal that the beneficial effect of SS-31 on oocyte quality from advanced age is mainly mediated by restoration of mitochondrial function, mitophagy and anti-aging metabolites. It provides a potential strategy for improving oocyte quality to extend the reproductive lifespan of female animals. The underlying mechanism of SS-31 improving the quality of maternally aged oocytes in mouse. SS-31 supplementation effectively improves meiotic maturation of aged oocytes by maintaining normal spindle/chromosome structure, whereas reducing oocyte aneuploidy, ROS accumulation and DNA damage. In particular, SS-31 enhances mitophagy activity and mitochondrial function, and increases anti-aging metabolites, such as spermidine and GSH in aged oocytes.
Xiong et al. (Thu,) studied this question.