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对氧化物纳米颗粒的机械洞察力通过H3K9me3调制诱导胚胎毒性

Xuemei Liu¹, Jie Li², Ling Zhu¹

¹Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China.

|June 29, 2024

概括

氧化纳米颗粒 (ZnONPs) 损害了早期胚胎发育,并降低了干细胞的潜力. 这些纳米粒子通过表观遗传变化破坏基因表达,影响生殖健康.

科学领域:

生殖毒理学生殖毒理学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
纳米医学的安全性

背景情况:

纳米粒子 (NP) 的使用越来越多,引发了生殖健康方面的担忧.
氧化纳米颗粒 (ZnONPs) 对植入前小鼠胚胎具有显著的毒性.
水平升高与辅助生殖技术 (ART) 的不良结果相关.

研究的目的:

研究ZnONPs对植入前胚胎发育的影响.
阐明ZnONPs胚胎毒性的潜在表观遗传机制.
评估H3K9me3抑制的潜力,以逆转ZnONPs的毒性.

主要方法:

植入前胚胎的体内和体外暴露模型.
鼠标胚胎干细胞 (mESC) 多能性测试 (teratoma 和 chimera).
多omics分析:RNA-Seq,CUT&Tag,ATAC-seq;生化分析 (拉向下拉,免疫沉).

主要成果:

暴露于ZnONPs会影响胚胎发育,并降低mESC多能性.
暴露于ZnONPs增加了H3K9me3水平,导致异色染色体的形成和抑制基因表达.
柴托辛是一种H3K9me3抑制剂,可以逆转ZnONPs诱导的胚胎毒性.
证实了ZnONPs和H3K9me3之间的直接相互作用.

结论:

ZnONPs通过表观遗传破坏H3K9me3.3产生胚胎毒性.
了解这些机制对于评估ZnONPs的生殖风险至关重要.
结果提供了纳米粒子毒性和人类生殖健康的见解.

关键词:

胚胎干细胞是一种胚胎干细胞.H3k9me3 3 的时间.多个omics的多个omics.在植入前的胚胎.这就是ZnONPs.

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