在子宫表皮中过度的脂质过氧化会导致植入失败和怀孕流产
Yafang Lu1, Yuhan Shao2,3, Weiwei Cui4
1Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 3, 2023
概括
保护子宫氧化还原平衡是成功植入胚胎的关键. 在子宫上皮细胞中删除Glutathione peroxidase 4 (GPX4) 通过增加脂质过氧化导致不孕,突出了GPX4.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生理学 细胞生理学
- 氧化应激研究研究 氧化应激研究
背景情况:
- 子宫的受容性对于怀孕早期的成功至关重要.
- 氧化还原稳定,特别是脂质过氧化物水平,对细胞功能至关重要.
- 在子宫受体性和胚胎植入方面,氧化还原平衡的具体作用以前尚不清楚.
研究的目的:
- 在胚胎植入过程中调查谷氨酸过氧化酶4 (GPX4) 在子宫上皮细胞中的作用.
- 为了确定脂质过氧化对子宫受体性和早期怀孕的影响.
- 探索与氧化还原失衡相关的植入缺陷的潜在治疗策略.
主要方法:
- 在小鼠中使用乳酸转移素 (Ltf) -Cre驱动剂对Gpx4进行子宫特异性删除.
- 脂质过氧化抑制剂的使用.
- 植入成功的评估和子宫受体性标志物.
- 对蛋白质碳化和脂质反应性氧物种水平的分析.
主要成果:
- 对于子宫表皮的特定删除GPX4导致不孕症,以缺陷植入为特征.
- 在Gpx4被删除的小鼠中观察到子宫表皮中的脂肪过氧化增加.
- 脂质过氧化抑制剂未能挽救植入,这表明更深层的分子损伤.
- 与GPX4删除保持生殖能力的Acyl-CoA合成酶长链家族成员4 (ACSL4) 的同时表达,表明了复杂的相互作用.
结论:
- 不平衡的氧化还原信号,特别是子宫上皮细胞中的高脂类过氧化,会对胚胎植入产生不利影响.
- GPX4对于维持子宫受体性和成功怀孕至关重要.
- 向和减少脂质过氧化物可能为预防植入失败提供治疗途径.
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