通过DNA甲基化重编程调解,通过早年p,p'-DDE暴露引起的跨代糖尿病效应
Shuo Wang1, Jingjing Wu1, Zhong Chen2
1School of Public Health, Hangzhou Normal University, 2318 Yuhangtang Road, Hangzhou, China.
Chemosphere
|December 13, 2023
概括
早期接触p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) 会增加跨代糖尿病的风险. 这发生在精子DNA的遗传表观遗传变化中,影响葡萄糖代谢基因.
科学领域:
- 环境表观遗传学环境表观遗传学
- 发育毒理学 发展毒理学
- 代谢性疾病研究研究
背景情况:
- 不利的早期生活环境可以在表观遗传上改变与糖尿病相关的基因,增加易感性.
- 作为DDT分解产物p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) 与糖尿病有关,但其机制尚不清楚.
研究的目的:
- 研究早期p,p'-DDE暴露对糖尿病易感性的跨代影响.
- 阐明DNA甲基化在调解这些跨代效应中的作用.
主要方法:
- 怀孕的老鼠从怀孕第8天到第15天暴露在p,p'-DDE中.
- 在后代中分析了精子DNA甲基组和葡萄糖代谢基因 (Gck,G6pc).
- 在不同世代 (F1和F2) 中跟踪表观遗传修饰.
主要成果:
- 早期的p,p'-DDE暴露通过男性生殖系遗传增加了跨代糖尿病易感性.
- 在F1后代的精子DNA甲基化模式因子宫内p,p'-DDE暴露而改变.
- 血糖代谢基因的甲基化差异在几代人的精子和肝脏中被观察到.
结论:
- 基因甲基化是从早期生活中p,p'-DDE暴露的跨代糖尿病效应的关键媒介.
- 发育过程中的环境因素可以诱导影响代谢健康的遗传性表观遗传变化.
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