Cao Xiaolong, Li Yameng, Liu Xiaoyu, Li Kepiao, Hong Shuang, Chen Haolei, Rao Qinxiong, Li Huaxi, Deng Zhongsheng, Song Weiguo
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.
Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China; Shanghai Service Platform of Agro-products Quality and Safety Evaluation Technology, Shanghai 201106, China.
J Hazard Mater. 2025 Aug 15;494:138744. doi: 10.1016/j.jhazmat.2025.138744. Epub 2025 May 26.
Previous studies have shown that perfluorooctane sulfonic acid (PFOS) and its new substitutes perfluorobutanesulfonic acid (PFBS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were associated with neurological abnormalities. However, many of these were conducted at concentrations higher than environmental levels, thus causing overt toxicity. This study employed multi-omics (transcriptomics and targeted metabolomics), morphological, behavioral and neuropathological methods to assess zebrafish embryos exposed to environmentally relevant concentrations (ERC) (10 and 100 ng/L), aiming to better elucidate the key molecular mechanisms that induce neurotoxic effects at ERC. Early development indicators and behavioral analyses showed that these three substances negatively impacted zebrafish development and inhibited locomotor behavior. Neuropathology and transcriptomics indicated that they disrupted visual phototransduction and lysosomal pathways, leading to the destruction of Nissl bodies, myelin sheaths and retinal structures, which were related to the abnormal transcription of relevant genes. Furthermore, targeted metabolomics demonstrated that they caused neurotoxicity by increasing the content of kynurenine and decreasing the content of asparagine and histidine. These findings indicated that they had similar neurotoxic effects, but the mechanisms may differ slightly. Collectively, this study will provide novel insights into understanding the mechanisms by which ERC of PFOS and its substitutes produce neurodevelopmental toxicity.
先前的研究表明，全氟辛烷磺酸（PFOS）及其新替代品全氟丁烷磺酸（PFBS）和6:2氯化多氟醚磺酸盐（6:2 Cl-PFESA）与神经异常有关。然而，其中许多研究是在高于环境水平的浓度下进行的，因此导致了明显的毒性。本研究采用多组学（转录组学和靶向代谢组学）、形态学、行为学和神经病理学方法，评估暴露于环境相关浓度（ERC）（10和100 ng/L）的斑马鱼胚胎，旨在更好地阐明在ERC下诱导神经毒性作用的关键分子机制。早期发育指标和行为分析表明，这三种物质对斑马鱼发育产生负面影响，并抑制运动行为。神经病理学和转录组学表明，它们破坏了视觉光转导和溶酶体途径，导致尼氏体、髓鞘和视网膜结构的破坏，这与相关基因的异常转录有关。此外，靶向代谢组学表明，它们通过增加犬尿氨酸含量和降低天冬酰胺和组氨酸含量而导致神经毒性。这些发现表明，它们具有相似的神经毒性作用，但机制可能略有不同。总的来说，本研究将为理解PFOS及其替代品的ERC产生神经发育毒性的机制提供新的见解。
