Abstract：
Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in varieties of products and tend to accumulate in the human body including umbilical cord blood and embryos/fetuses. In this study, we conducted an assessment and comparison of the potential early developmental toxicity of perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid, perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate, and perfluorobutyric acid at noncytotoxic concentrations relevant to human exposure using models based on human embryonic stem cells in both three-dimensional embryoid body (EB) and monolayer differentiation configurations. All six compounds influenced the determination of cell fate by disrupting the expression of associated markers in both models and, in some instances, even led to alterations in the formation of cystic EBs. The expression of cilia-related gene IFT122 was significantly inhibited. Additionally, PFOS and PFOA inhibited ciliogenesis, while PFOA specifically reduced the cilia length. Transcriptome analysis revealed that PFOS altered 1054 genes and disrupted crucial signaling pathways such as WNT and TGF-β, which play integral roles in cilia transduction and are critical for early embryonic development. These results provide precise and comprehensive insights into the potential adverse health effects of these six PFAS compounds directly concerning early human embryonic development.
摘要：
全氟烷基和多氟烷基物质（PFAS）广泛用于多种产品中，并倾向于在人体中积累，包括脐带血和胚胎/胎儿。在这项研究中,我们对全氟辛酸（PFOA）的潜在早期发育毒性进行了评估和比较，十一氟己酸（PFHxA），七氟丁酸，全氟辛烷磺酸盐(PFOS)，全氟己磺酸盐，使用基于三维胚状体（EB）和单层分化构型的人类胚胎干细胞的模型，与人类暴露相关的非细胞毒性浓度的全氟丁酸。所有六种化合物都通过破坏两个模型中相关标记的表达来影响细胞命运的确定，在某些情况下,甚至导致囊性EBs形成的改变。纤毛相关基因IFT122的表达受到显著抑制。此外,PFOS和PFOA抑制纤毛生成，而PFOA特别减少了纤毛长度。转录组分析显示，全氟辛烷磺酸改变了1054个基因，破坏了WNT和TGF-β等关键信号通路，它们在纤毛转导中起着不可或缺的作用，对早期胚胎发育至关重要。这些结果提供了对这六种PFAS化合物直接涉及人类早期胚胎发育的潜在不利健康影响的精确和全面的见解。
