6:2 氟调聚物醇 (6:2 FTOH) 是用于制造短链多氟烷基物质和全氟烷基物质的原料。我们之前的研究表明，妊娠期暴露于 6:2 FTOH 会损害后代的血脑屏障 (BBB) 功能，并伴有焦虑样行为和学习记忆缺陷。本研究的目的是进一步探讨母体暴露于 6:2 FTOH 导致子代小鼠 BBB 功能受损的具体机制。从妊娠第 8.5 天直至分娩，怀孕小鼠口服不同剂量的 6:2 FTOH（0、5、25 和 125 mg/kg/天）。这些结果证实母体 6:2 FTOH 暴露会损害 BBB 功能并扰乱大脑免疫微环境。随后的研究表明，子代脑微血管内皮的内皮间质转化（EndMT）可能是介导血脑屏障功能破坏的机制。机制研究表明，接触 6:2 FTOH 通过肿瘤坏死因子-α/细胞外信号调节激酶 1/2 信号通路上调 ETS 原癌基因 1 (ETS1) 表达，介导能量代谢紊乱，导致肌动蛋白受损动力学并随后触发 EndMT 表型。这是第一个发现，表明妊娠期 6:2 FTOH 暴露通过 ETS1 介导的脑微血管内皮细胞的 EndMT 导致 BBB 功能受损，可能为神经发育障碍的环境起源提供新的见解。© 2024。作者，获得 Springer Science Business Media, LLC（Springer Nature 的一部分）的独家许可。

6:2 Fluorotelomer alcohol (6:2 FTOH) is a raw material used in the manufacture of short-chain poly- and perfluoroalkyl substances. Our previous study revealed that gestational exposure to 6:2 FTOH can impair blood‒brain barrier (BBB) function in offspring, accompanied by anxiety-like behavior and learning memory deficits. The aim of this study was to further investigate the specific mechanism by which maternal exposure to 6:2 FTOH resulted in impaired BBB function in offspring mice. Pregnant mice were orally administered different doses of 6:2 FTOH (0, 5, 25, and 125 mg/kg/day) from gestation day 8.5 until delivery. These results confirmed that maternal 6:2 FTOH exposure impaired BBB function and disrupted the brain immune microenvironment. Subsequent investigations revealed that endothelial-to-mesenchymal transition (EndMT) in the cerebral microvascular endothelium of offspring may be the mechanism mediating functional disruption of the BBB. Mechanistic studies revealed that exposure to 6:2 FTOH upregulated ETS proto-oncogene 1 (ETS1) expression via the tumor necrosis factor-α/extracellular signal-regulated kinase 1/2 signaling pathway, which mediated disturbances in energy metabolism, leading to impaired actin dynamics and subsequently triggering the EndMT phenotype. This is the first finding indicating that gestational 6:2 FTOH exposure caused functional impairment of the BBB through ETS1-mediated EndMT in cerebral microvascular endothelial cells, potentially providing novel insight into the environmental origins of neurodevelopmental disorders.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.