α-tocopherol deficiency in follicular ovarian cyst (FOCs) follicular fluid (FF) elevates oxidative stress and impairs oocyte maturation.

Abstract

Follicular ovarian cysts (FOCs) are prevalent reproductive disorders in both humans and animals, especially in livestock, where they cause economic losses by reducing fertility and productivity. FOCs are marked by a dominant follicle that fails to ovulate, disrupting the estrous cycle and reproductive efficiency. Previous studies indicate that the follicular fluid (FF) in cystic ovaries shows oxidative imbalance, affecting oocyte quality by altering glutathione peroxidase (GPX1) and selenium pathways. However, the metabolic profile of FF in cystic ovaries needs further exploration. This study examined oxidative stress and metabolic changes in FOC pathogenesis. Using untargeted metabolomics of goat FF, we found significant differences in 12,741 metabolites between cystic and control FF. Cystic FF had reduced levels of α-tocopherol and 8'-apocaroten-8'-ol, key for oxidative stress management, and increased levels of mycotoxins (e.g., Deoxynivalenol-3-glucoside) and long-chain fatty acids. Adding 200 μM α-tocopherol to FOC FF oocyte cultures doubled oocyte maturation rates and decreased reactive oxygen species (ROS). Metabolomic analysis linked low α-tocopherol to high lipid peroxyl radicals and low glutathione oxidation, emphasizing oxidative stress regulation's importance in the follicular microenvironment. Our findings suggest that α-tocopherol may serve as a biomarker and therapeutic agent to enhance oocyte maturation in FOCs.