Su Xiaoli, He Yijing, Li Heran, Yu Tianhang, Sun Qinfeng, Chen Miaoyu, Zhang Biao, Wang Weihan, Ju Shiqiang, Li Qiao
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Food Chem Toxicol. 2025 Jan;195:115122. doi: 10.1016/j.fct.2024.115122. Epub 2024 Nov 20.
Cottonseed meal (CSM) is an ideal source of protein feed ingredients. However, the gossypol contained in it has toxic effects on animals, limiting its use in livestock production. The underlying mechanisms remain largely unknown. This study aimed to investigate the adverse effects of gossypol exposure and assess whether melatonin, a natural antioxidant, could alleviate oocyte damage induced by gossypol. Porcine cumulus oocyte complexes (COCs) were treated with gossypol alone or co-treated with melatonin for 44 h during in vitro maturation. The results demonstrated that gossypol exposure induced oxidative stress and mitochondrial dysfunction, leading to oocyte maturation failure. Conversely, melatonin co-treatment mitigated these detrimental effects, by promoting oocyte mitophagy, as evidenced by the upregulation of PINK1, Parkin, and LC3 expressions, along with the downregulation of P62. Further investigation revealed that gossypol treatment significantly decreased SIRT1 protein expression, while melatonin co-treatment markedly increased it. Using the SIRT1 inhibitor Ex527 confirmed that melatonin enhances mitophagy through SIRT1, improving mitochondrial function and rescuing oocyte maturation. This study revealed the potential harm of gossypol on mammalian reproductive health, provided experimental reference for the protective effect of melatonin, and provided theoretical basis for the effective prevention and treatment of reproductive damage caused by gossypol.
棉籽粕是蛋白质饲料原料的理想来源。然而，其中含有的棉酚对动物具有毒性作用，限制了其在畜牧生产中的应用。其潜在机制在很大程度上仍不清楚。本研究旨在探讨棉酚暴露的不良影响，并评估天然抗氧化剂褪黑素是否可以减轻棉酚诱导的卵母细胞损伤。猪卵丘卵母细胞复合体（COCs）在体外成熟过程中单独用棉酚处理或与褪黑素共同处理44小时。结果表明，棉酚暴露诱导氧化应激和线粒体功能障碍，导致卵母细胞成熟失败。相反，褪黑素共同处理减轻了这些有害影响，通过促进卵母细胞线粒体自噬，PINK1、Parkin和LC3表达上调以及P62表达下调证明了这一点。进一步研究表明，棉酚处理显著降低SIRT1蛋白表达，而褪黑素共同处理则显著增加其表达。使用SIRT1抑制剂Ex527证实褪黑素通过SIRT1增强线粒体自噬，改善线粒体功能并挽救卵母细胞成熟。本研究揭示了棉酚对哺乳动物生殖健康的潜在危害，为褪黑素的保护作用提供了实验参考，并为有效预防和治疗棉酚引起的生殖损伤提供了理论依据。
