Polyamine metabolite spermidine rejuvenates the oocyte quality by enhancing mitophagy during female reproductive aging
Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age. Overall design: To gain insight into the potential mechanisms regarding how spermidine improves the quality of aged oocytes, micro-transcriptome was carried out to compare the change of young, aged and spermidine-rescue group transcript levels.