Hexafluoropropylene oxide trimer acid (HFPO-TA) disturbs embryonic liver and biliary system development in zebrafish

• Published in: The Science of the total environment 2023-02, Vol.859 (Pt 1), p.160087, Article 160087
• Main Authors: Sun, Sujie, Li, Xue, Zhang, Li, Zhong, Zilin, Chen, Chao, Zuo, Yuhua, Chen, Yu, Hu, Hongmei, Liu, Fasheng, Xiong, Guanghua, Lu, Huiqiang, Chen, Jianjun, Dai, Jiayin
• Format: Article
• Language: English
• Subjects: Animals; Bile Acids and Salts; Biliary system; Biliary Tract; Fluorocarbons - toxicity; Hexafluoropropylene oxide trimer acid; Lipid metabolism; Liver; Liver development; Zebrafish; Zebrafish embryos
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2022.160087

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has emerged as a potential environmental pollutant. Here, to investigate the toxic effects of HFPO-TA on liver and biliary system development, zebrafish embryos were exposed to 0, 50, 100, or 200 mg/L HFPO-TA from 6 to 120 h post-fertilization (hpf). Results showed that the 50 % lethal concentration (LC50) of HFPO-TA was 231 mg/L at 120 hpf, lower than that of PFOA. HFPO-TA exposure decreased embryonic hatching, survival, and body length. Furthermore, HFPO-TA exerted higher toxicity at the specification stage than during the differentiation and maturation stages, leading to small-sized livers in Tg(fabp10a: DsRed) transgenic larvae and histopathological changes. Significant decreases in the mRNA expression of genes related to liver formation were observed. Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) levels were significantly increased. HFPO-TA decreased total cholesterol (TCHO) and triglyceride (TG) activities, disturbed lipid metabolism through the peroxisome proliferator-activated receptor (PPAR) pathway, and induced an inflammatory response. Furthermore, HFPO-TA inhibited intrahepatic biliary development in Tg(Tp1:eGFP) transgenic larvae and interfered with transcription of genes associated with biliary duct development. HFPO-TA reduced bile acid synthesis but increased bile acid transport, resulting in disruption of bile acid metabolism. Therefore, HFPO-TA influenced embryonic liver and biliary system morphogenesis, caused liver injury, and may be an unsafe alternative for PFOA. [Display omitted] •HFPO-TA exposure causes small liver formation.•HFPO-TA disturbs Notch, Nodal, and Wnt/β-catenin signaling pathways involved in liver and biliary system development.•HFPO-TA alters gene expression of PPAR signaling pathway, resulting in lipid metabolism disruption and inflammatory response.•HFPO-TA reduces bile acid synthesis but promotes bile acid transport.