一种系统毒理学方法涉及转录后调节网络在PFAS暴露后的生殖缺陷中
Abigail P Bline1, Hui Jiang2, Max Levenson1
1Molecular Toxicology Interdepartmental Program, UCLA, Los Angeles, CA. 90095.
概括
和多醇基物质 (PFAS) 通过破坏细胞液态结构,损害胚胎细胞的发育和功能. 这项对C. elegans的研究揭示了这些持久性环境化学物质的生殖毒性机制.
科学领域:
- 环境毒理学环境毒理学
- 发展生物学 发展生物学
- 分子毒理学 分子毒理学
背景情况:
- 和多醇基物质 (PFAS) 是持久性环境污染物,毒理学数据有限,特别是关于生殖细胞发育和未来生育能力的数据.
- 了解PFAS的生殖毒性至关重要,因为它们在环境和消费品中广泛存在.
研究的目的:
- 在生殖细胞发育过程中,比较遗留PFAS (PFOS) 和化以太类似物 (6:2 Cl-PFESA) 的生殖毒性.
- 通过使用Caenorhabditis elegans.来研究PFAS诱导的生殖毒性背后的分子机制.
主要方法:
- 对PFOS和6:2 Cl-PFESA对C. elegans生殖细胞数量,细胞亡和介质性进展的影响进行比较分析.
- 评估发育暴露成人的后代的胚胎死亡率.
- RNA测序 (mRNA和小RNA) 用于识别生殖系调节网络中的分子扰动.
主要成果:
- 暴露于PFOS和6:2Cl-PFESA都减少了生殖细胞数量,增加了生殖细胞线的亡,并引起了介质缺陷.
- 发育性暴露导致后代胚胎死亡率增加.
- 暴露于PFAS破坏了非编码RNA介导的生殖系调节和P颗粒,影响了RNA-蛋白质类液态凝结物.
- 在PFAS和突变突变突变突变突变之间观察到显著的基因环境相互作用,加剧了胚胎死亡率.
结论:
- 暴露于PFAS会对生殖细胞的发育和功能产生负面影响,导致生殖毒性.
- 类似液体的细胞凝聚物 (P颗粒,突触体复合物) 的破坏是PFAS生殖毒性的关键机制.
- PFAS的物理化学特性可能有助于其多样化的生物效应,突出显示需要进一步进行毒理学评估.
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