6‐Gingerol and Astaxanthin Mitigate the Effects of Stearic Acid in Pig Oocyte Maturation

ABSTRACT Elevated non‐esterified fatty acids (NEFAs), particularly stearic acid (SA), have a deleterious effect on oocyte maturation, leading to developmental damage and reproductive issues. High SA levels disrupt metabolic processes, inducing lipotoxicity that impairs oocyte quality and contributes to reproductive failures through early embryonic losses. This research investigates the lipotoxic effects of SA and assesses the protective potential of 6‐Gingerol (6‐G) and Astaxanthin (AX) on porcine oocytes during in vitro maturation (IVM). Herein, 6100 cumulus‐oocyte complexes (COCs) were exposed to various concentrations of SA (25–250 μM) to elucidate the concentration‐dependent effect on oocyte viability, polar body extrusion (PBE) and cumulus cell expansion index (CCEI). However, the efficacy of 6‐G (5–15 μM) and AX (2.5 μM) in combination with SA at 150 μM (SA6) concentration was evaluated to mitigate these adverse effects. The results indicated that SA6 substantially reduced oocyte viability, PBE and CCEI, demonstrating its toxic impact on oocyte developmental competence ( p < 0.0001). Moreover, treatment with antioxidants such as SA6 + 6‐G (10 μM) and SA6 + AX showed a considerable increase in viability and PBE compared to SA6 alone ( p < 0.05). These findings demonstrate the importance of lipid metabolism in oocyte health, where dysregulation impairs reproductive capacity. Both 6‐G and AX protected against lipotoxicity induced by SA6 while enhancing lipid homeostasis and the anti‐oxidative defences necessary for maintaining cellular integrity. This study finds substantial evidence that optimising the microenvironment with specific antioxidants can improve oocyte quality and provide invaluable knowledge in reproductive technologies and fertility treatments.