Wu Linlin, Wang Jian, Ye Heyong, Yao Yiyang, Hu Miaoyang, Cheng Jie, Kong Lingcan, Liu Wenwei, Ge Feng
The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China; The Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Jiangwangmiao Street 8, Nanjing 210042, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117424. doi: 10.1016/j.ecoenv.2024.117424. Epub 2024 Nov 30.
Hexafluoropropylene oxide oligomer acids (HFPOs), an emerging environmental pollutant, are increasingly utilized in the manufacture of fluorinated synthetic materials as a substitute for traditional perfluorooctanoic acid (PFOA), resulting in a corresponding rise in detection rates in aquatic environments, which may present inherent safety hazards to ecosystems and public health. However, few data are available on the issue of their toxicity and mechanism. This study aimed to investigate the potential toxic effects of hexafluoroepoxypropane tetrameric acid (HFPO-TeA), a typical HFPO, on the early developmental stages of zebrafish larvae. It revealed that HFPO-TeA exposure resulted in significant detrimental effects, including adverse impacts on general morphological characteristics, such as eye area, heart rate, and swimming bladder, in zebrafish embryos and larvae. Targeted metabolomics and transcriptomics inquiries clarified that HFPO-TeA exposure reduced the levels of the neurotransmitter gamma-aminobutyric acid (GABA) and downregulated the expression of genes related to the GABA pathway. Simultaneously, transgenic zebrafish exhibited that exposure to HFPO-TeA impedes the growth of GABAergic neurons. Moreover, the molecular docking analysis indicated that GABAA receptors might be the potential targets of HFPO-TeA. Taken together, the current data highlights that the HFPO-TeA might not be safe alternatives to PFOA. This study presented a model for HFPO-TeA-induced neurotoxicity in developing zebrafish that can aid in ecological risk assessments.
六氟环氧丙烷低聚物酸（HFPOs）是一种新兴的环境污染物，作为传统全氟辛酸（PFOA）的替代品，越来越多地用于制造含氟合成材料，导致其在水生环境中的检出率相应上升，这可能对生态系统和公众健康构成潜在安全隐患。然而，关于其毒性和作用机制的相关数据却很少。本研究旨在探究典型的HFPO——六氟环氧丙烷四聚酸（HFPO-TeA）对斑马鱼幼体早期发育阶段的潜在毒性作用。研究发现，暴露于HFPO-TeA会导致显著的有害影响，包括对斑马鱼胚胎和幼体的一般形态特征产生不利影响，如眼区、心率和鳔。靶向代谢组学和转录组学研究表明，暴露于HFPO-TeA会降低神经递质γ-氨基丁酸（GABA）的水平，并下调与GABA途径相关基因的表达。同时，转基因斑马鱼显示，暴露于HFPO-TeA会阻碍GABA能神经元的生长。此外，分子对接分析表明，GABAA受体可能是HFPO-TeA的潜在靶点。综上所述，目前的数据表明HFPO-TeA可能并非PFOA的安全替代品。本研究提出了一个HFPO-TeA诱导斑马鱼发育过程中神经毒性的模型，有助于进行生态风险评估。
