(54) Resolvin E1 Improves the Maturation of Porcine Oocytes by suppressing Oxidative Stress via Nrf2 Pathway Activation

Hyo-Gu Kang¹; Ji Hyeon Yun¹; Se-Been Jeon¹; Min Ju Kim¹; Pil-Soo Jeong¹; Kyungjun Uh¹; Bong-Seok Song¹; Sun-Uk Kim^{1, 2}; Bo-Woong Sim^{1, 2}

1. Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungcheongbuk-do 28116, Republic of Korea

2. Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Republic of Korea

Abstract Text:

Resolvin E1 (RvE1), a specialized pro-resolving mediator (SPM) lipid, has been detected in both follicular fluid and serum, and is secreted by cumulus cells during culture. Despite this, the role of RvE1 in mammalian oocyte maturation is not well understood. This study examined the antioxidant properties of RvE1 in meiotic progression and its underlying mechanisms. Supplementing RvE1 during in vitro maturation significantly enhanced cumulus cell expansion and the proportion of metaphase II oocytes compared to the control group. Post-parthenogenetic activation, RvE1-treated oocytes showed improved developmental competence, with higher cleavage, blastocyst formation, and cell survival rates, as well as increased cell counts. Our findings indicate that RvE1 treatment elevated Nrf2 protein levels, upregulated antioxidant-related genes (CATALASE, SOD1, SOD2, HO-1, NRF2), and reduced Keap1 protein and ROS levels in porcine cumulus cells and oocytes. Additionally, RvE1 treatment enhanced mitochondrial membrane potential and reduced mitochondrial-related apoptotic signaling. To explore the relationship between the Nrf2 pathway and RvE1's effects on oocyte maturation, we treated porcine oocytes with RvE1 and brusatol, an Nrf2-specific inhibitor, during maturation. Culturing cumulus cell-oocyte complexes in media with brusatol, both with and without RvE1, confirmed that brusatol reversed RvE1’s beneficial effects on developmental competence. These results suggest that RvE1 enhances oocyte quality by activating the Nrf2 signaling pathway, improving cumulus cell viability, and preventing apoptosis. This study provides novel insights into the mechanisms regulating oocyte maturation. This research was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM4252533, KGM1012521), Republic of Korea