在生命早期暴露在香烟烟雾中,使肺功能和DNA甲基化在Cyp1a1的变化发生在生命后期暴露时
Chinonye Doris Onuzulu1, Samantha Lee1, Sujata Basu2
1Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
概括
早期暴露于香烟烟雾 (CS) 导致后代肺部持续的DNA甲基化变化,影响肺功能和基因表达. 这些变化可以通过成人CS再暴露来恢复.
科学领域:
- 环境表观遗传学环境表观遗传学
- 呼吸系统医学 呼吸系统医学
- 发展性毒理学 发展性毒理学
背景情况:
- 产前和早期暴露于香烟烟雾 (CS) 与后代的长期健康问题有关,包括肺部发育受损和喘风险增加.
- 假设DNA甲基化 (DNAm) 变化能够调解这些效应,但很少有研究对肺组织中CS诱导的DNAm进行了研究,特别是对产前和产后暴露的区别.
研究的目的:
- 建立一个小鼠模型来隔离产前与产后早期CS暴露对后代肺部健康的影响.
- 调查早期CS暴露对肺功能,免疫细胞透以及*Cyp1a1*基因的DNAm和表达的影响.
主要方法:
- 开发了一种小鼠模型来控制产前和产后早期的CS暴露时间.
- 评估肺功能,免疫细胞透,DNAm,以及后代的*Cyp1a1*基因表达.
- 研究了这些变化在成年后的持续性以及成人再暴露的影响.
主要成果:
- 产前和产后早期的CS暴露诱导了后代肺功能,基因表达和肺 *Cyp1a1* DNAm的持久,长期的差异.
- 这些表观遗传变化随着时间的推移而减弱,但在成人CS再暴露后重新建立起来.
- 早期的CS暴露导致肺DNA甲基化模式在*Cyp1a1*的长期变化,这种变化持续到成年早期.
结论:
- 早期的CS暴露在肺部建立了长期的表观遗传修饰,影响呼吸系统健康.
- 鼠标模型为研究产前和产后早期CS暴露的特定影响提供了有价值的工具.
- 研究结果表明,虽然*Cyp1a1*的DNA甲基化变化可能会消失,但其他机制有助于从生命早期的CS暴露中长期呼吸记忆.
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