Maternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high‐fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice. Oral administration of melatonin to HFD mice not only reduces ROS generation, but also prevents spindle/chromosome anomalies in oocytes, consequently promoting the developmental potential of early embryos. Consistent with this finding, we find that melatonin supplement during in vitro maturation also markedly attenuates oxidative stress and meiotic defects in HFD oocytes. Finally, by performing morpholino knockdown and acetylation‐mimetic mutant overexpression assays, we reveal that melatonin ameliorates maternal obesity‐induced defective phenotypes in oocytes through the SIRT3‐SOD2‐dependent mechanism. In sum, our data uncover the marked beneficial effects of melatonin on oocyte quality from obese females; this opens a new area for optimizing culture system as well as fertility management.

中文翻译：

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褪黑素可通过SIRT3-SOD2依赖性途径预防母体肥胖相关的氧化应激和卵母细胞的减数分裂缺陷

人类孕产妇肥胖与整个生殖谱系的不良结果有关。新兴证据表明，这些缺陷可能归因于卵母细胞内的因素。尽管各种分子和途径可能导致卵母细胞质量受损，但如何预防与孕妇肥胖有关的生育问题仍然是一项挑战。使用高脂饮食（HFD）喂养的小鼠作为肥胖模型，我们记录了肥胖小鼠卵母细胞的纺锤体紊乱，染色体错位和活性氧（ROS）水平升高。向HFD小鼠口服褪黑激素不仅可以减少ROS的产生，而且还可以防止卵母细胞中的纺锤体/染色体异常，从而提高早期胚胎的发育潜力。与这个发现一致，我们发现褪黑激素补充剂在体外成熟过程中还可以显着减轻HFD卵母细胞的氧化应激和减数分裂缺陷。最后，通过进行吗啉代敲除和乙酰化模拟突变体过表达测定，我们发现褪黑激素通过SIRT3-SOD2依赖性机制改善了母体肥胖引起的卵母细胞缺陷表型。总之，我们的数据揭示了褪黑激素对肥胖女性卵母细胞质量的显着有益作用。这为优化养殖系统和生育管理开辟了一个新领域。我们发现褪黑激素可通过SIRT3‐SOD2依赖性机制改善母体肥胖引起的肥胖症表型缺陷。总之，我们的数据揭示了褪黑激素对肥胖女性卵母细胞质量的显着有益作用。这为优化养殖系统和生育管理开辟了一个新领域。我们发现褪黑激素可通过SIRT3‐SOD2依赖性机制改善母体肥胖引起的肥胖症表型缺陷。总之，我们的数据揭示了褪黑激素对肥胖女性卵母细胞质量的显着有益作用。这为优化养殖系统和生育管理开辟了一个新领域。