Cordycepin Delays Postovulatory Aging of Mammalian Oocytes through Inhibition of Maternal mRNAs Degradation via DCP1A Polyadenylation Suppression

Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rates of assisted reproductive technology (ART). Nevertheless, potential preventative strategies to improve aging oocytes quality and the associated underlying mechanisms warrant further investigation. In this study, we identify cordycepin, an natural nucleoside analogue, as having the potential to restore the postovulatory aging-induced decline in oocyte quality, including aspects such as oocyte fragmentation, embryonic developmental competence, spindle/chromosomes morphology and mitochondrial function. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Mechanistically, cordycepin was found to suppress the elevation of DCP1A protein levels by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin may prevent postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression, thereby promoting the successful rates of ART procedure.