Resolvin E1 improves the maturation of porcine oocytes by suppressing oxidative stress via Nrf2 pathway activation

Abstract

Resolvin E1 (RvE1) is a specialized pro-resolving mediator from the bioactive lipid family that has been detected in follicular fluid and serum and is secreted by cumulus cells during culture. However, its role in mammalian oocyte maturation remains poorly understood. We investigated the antioxidant function of RvE1 and its underlying mechanisms during meiotic progression. RvE1 significantly enhanced cumulus cell expansion and increased the rate of metaphase II oocytes compared to controls. Oocytes treated with RvE1 exhibited markedly improved developmental competence following parthenogenetic activation, as evidenced by higher cleavage and blastocyst formation rates, and higher cell numbers. Moreover, RvE1 increased the Nrf2 protein level and upregulated the expression of antioxidant-related genes (CAT, SOD1, SOD2, HO-1, and NRF2) in porcine cumulus cells and oocytes while decreasing Keap1 protein levels and reactive oxygen species. To elucidate the role of Nrf2 signaling further, porcine oocytes were treated with RvE1 in the presence of the Nrf2-specific inhibitor brusatol during maturation, and cumulus cell-oocyte complexes were cultured in media with or without RvE1. Notably, the beneficial effects of RvE1 on developmental competence were reversed by the brusatol treatment. These findings indicate that RvE1 activates the Nrf2 signaling pathway, thereby enhancing the viability of cumulus cells and preventing apoptosis, which ultimately improves follicular quality. This study provides new insights into the mechanisms regulating follicular maturation.