Chronic stress which is common in the current society can be harmful to female reproduction and is associated with oocyte defects. However, the underlying mechanisms remain largely unknown. Herein, by using a mouse model of chronic restraint stress, we demonstrated that chronic stress could induce meiotic spindle abnormalities, chromatin misalignment, mitochondrial dysfunction and elevated ROS levels in oocytes in vivo, all of which were normalized by the administration of melatonin. Consistently, melatonin treatment during in vitro maturation also attenuated the meiotic defects induced by H₂O₂ by regulating autophagy and SIRT1, which could be abolished by SIRT1 inhibitor, Ex527 and autophagy inhibitor Bafilomycin A1 (Baf A1). These data indicate that melatonin can mitigate chronic stress-induced oxidative meiotic defects in mice MII oocytes by regulating SIRT1 and autophagy, providing new understanding for stress-related meiotic errors in MII oocytes and suggesting melatonin and SIRT1 could be new targets for optimizing culture system of oocytes as well as fertility management.

当前社会常见的慢性压力可能对女性生殖有害，并与卵母细胞缺陷有关。然而，潜在的机制在很大程度上仍然未知。在此，通过使用慢性束缚应激的小鼠模型，我们证明了慢性应激可在体内诱导卵母细胞减数分裂纺锤体异常、染色质错位、线粒体功能障碍和 ROS 水平升高，所有这些都通过褪黑激素的给药而正常化。始终如一地，体外成熟过程中的褪黑激素处理也减弱了由 H ₂ O ₂诱导的减数分裂缺陷通过调节自噬和 SIRT1，这可以被 SIRT1 抑制剂 Ex527 和自噬抑制剂 Bafilomycin A1 (Baf A1) 消除。这些数据表明，褪黑激素可以通过调节 SIRT1 和自噬来减轻小鼠 MII 卵母细胞中慢性应激诱导的氧化减数分裂缺陷，为 MII 卵母细胞中与应激相关的减数分裂错误提供了新的理解，并表明褪黑激素和 SIRT1 可能是优化培养系统的新靶点。卵母细胞以及生育管理。