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在基于人类iPSC的3D模型中,遗留PFAS的胚胎毒性和混合物效应

Andreas Frederik Treschow¹, Elisa Martiny¹, Claudia Torero Gutierrez¹

¹National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark.

Cell biology and toxicology

|January 19, 2026

概括

通过损害心肌细胞分化,四种per-和多醇基物质 (PFAS) 证明了胚胎毒性. 它们的综合效应是随着度的增加而产生的,这表明它们在人类发育中具有共同的分子作用.

科学领域:

环境科学环境科学
毒理学毒理学毒理学
发育生物学发展生物学

背景情况:

人类面临不断暴露于外源化学物质,包括持久性per-和多基基物质 (PFAS).
PFAS与人类发育的不良影响有关,需要强大的毒性测试模型.
遗留的PFAS (PFOS,PFOA,PFNA,PFHxS) 特别令人担忧,因为它们的持久性和广泛存在.

研究的目的:

用3D人类诱导多能干细胞 (hiPSC) 模型评估四种遗留PFAS的个人和混合胚胎毒性作用.
确定这些PFAS在人类早期发育过程中诱导的生物积累和基因表达变化.
评估混合物效应是否与度添加原则保持一致.

主要方法:

使用基于3DhiPSC模型的PluriLum测定,用于对PFOS,PFOA,PFNA和PFHxS的胚胎毒性测试.
确定了个别的PFAS强度,并将其评估在等效和现实度混合物中.
在3D胚胎体中进行吸收研究,并进行RNA测序以分析基因表达变化.

主要成果:

PFNA表现出最高的个人胚胎毒性强度,其次是PFOS,PFOA和PFHxS.
混合物反应与所有测试度的度添加性一致.
PFOS的生物积累量最高,而RNA测序显示了与心脏和肌肉组织发育相关的途径的显著变化,特别是与PFOS暴露.

结论:

四种经过测试的遗留PFAS诱导显著的胚胎毒性,主要是通过损害心肌细胞分化.
使用度加法原理,可以预测PFAS混合物的联合毒理效应.
共同的功能途径和共同的分子作用部位是PFAS引起的发育毒性的基础.

关键词:

一个心肌细胞.胚胎毒性胚胎毒性混合物的毒性混合物的毒性在PFAS的采用上.在PFHxS中使用.这就是PFNA的PFNA.这就是PFOA的PFOA.在PFOS系统中,我们可以这就是hiPSCs.

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