表观遗传修饰与的跨代遗传有关:小鼠卵细胞中的生殖毒性
Jiaqiao Zhu1,2,3,4, Shuai Guo1, Jiangqin Cao1
1College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
International journal of molecular sciences
|October 26, 2024
概括
母亲暴露于会改变后代卵细胞的表观遗传,增加DNA损伤和减少DNA修复. 这影响了卵细胞质量,成熟和早期胚胎发育,表明生殖毒性的跨代遗传.
科学领域:
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 毒理学 毒理学 毒理学
背景情况:
- 母亲暴露于会对后代的发育产生负面影响.
- 对后代卵子细胞的特定影响和潜在机制尚不清楚.
研究的目的:
- 研究母体暴露对后代卵子细胞表观遗传修饰和质量的影响.
- 阐明影响卵细胞成熟和早期胚胎发育的机制.
主要方法:
- 在怀孕期间,小鼠暴露于.
- 对后代卵细胞进行了表观遗传修饰 (H3K4me2,H4K12ac,H19的DNA甲基化),DNA损伤 (γH2AX),DNA修复 (DNA-PKcs),ROS水平和线粒体活动的分析.
- 评估了卵细胞介质成熟和早期胚胎发育.
- 在后代的卵巢上进行了RNA测序 (RNA-seq).
主要成果:
- 母亲暴露导致H3K4me2和H4K12ac的减少,并在后代卵细胞中增加H19DNA甲基化.
- 观察到DNA损伤增加 (γH2AX) 和DNA修复减少 (DNA-PKcs),尽管ROS和线粒体活动正常.
- 卵细胞质量,介质成熟和早期胚胎发育受损.
- RNA-seq检测显示,后代卵巢的基因表达发生变化,与代谢,信号转导和内分泌调节有关.
结论:
- 母亲暴露于会诱导后代卵细胞的表观遗传变化和DNA损伤,损害其质量和功能.
- 这些变化破坏了卵细胞成熟和早期胚胎发育,这表明表观遗传修饰在的生殖毒性中发挥了作用.
- 这些发现提供了对老鼠生殖细胞中的生殖毒性转代表观遗传的证据.
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