Eicosapentaenoic Acid Improves Porcine Oocyte Cytoplasmic Maturation and Developmental Competence via Antioxidant and Mitochondrial Regulatory Mechanisms

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus-oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of <i>TNF-α</i> and <i>BAX</i> and upregulation of <i>BCL2</i>. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing <i>SOD2</i> and <i>GPX4</i> expression. Mitochondrial quality and turnover were improved via upregulation of <i>PPARGC1A</i>, <i>NDUFS2</i>, <i>PINK1</i>, <i>LC3</i>, <i>FIS1</i>, <i>MUL1</i>, and <i>OPA1</i>, alongside strengthened ER-mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose-response relationships using expanded embryo-quality endpoints.