mTOR signaling mediates energy metabolic equilibrium in bovine and mouse oocytes during the ovulatory phase†

The mammalian target of rapamycin (mTOR) signaling pathway is activated by luteinizing hormone in preovulatory follicle. However, its impact on ovulation remains inadequately explored. Utilizing in vivo studies and in vitro fertilization, we demonstrated that the negative effect of inhibition of mTOR signaling by rapamycin on oocyte quality during the ovulatory phase, with a notable decrease in the total cell count of blastocysts, a reduction in gastrula size, and fetal degeneration on the 16th day of gestation while not affecting ovulated oocyte count or granulosa cell luteinization. Mechanistically, our study elucidated that in the ovulatory phase, mTOR signaling inhibition enhances lipid consumption, mitochondrial membrane potential of oocytes, and ATP generation. As a result, embryos derived from these oocytes exhibit higher levels of reactive oxygen species, insufficient energy supply, and lower developmental potency. Furthermore, the impact of mTOR signaling on oocytes remains consistent across various species, and its inhibition has been demonstrated to enhance energy metabolism during the in vitro maturation process of bovine oocytes. These findings demonstrate the critical role of mTOR signaling during the ovulatory phase in balancing oocyte energy metabolism, enriching our understanding of the role of mTOR on ovulation regulation.