Perfluorohexane sulfonate exposure caused multiple developmental abnormalities in early life of zebrafish

Perfluorohexane sulfonate (PFHxS) has been listed as a new persistent organic pollutant since 2022. Although the production and use of PFHxS are now restricted, it remains highly persistent in aquatic environments for decades. However, so far research about the toxic effects on early-life exposure of PFHxS and underlying mechanisms are still limited. In this study, we employed both wild type and specifically labeled transgenic zebrafish as model to investigate the developmental toxicity of PFHxS during early-stage exposure in zebrafish. A series of phenotypic and molecular indicators were analyzed at various time points between 24 h post-fertilization (hpf) and 7 days post-fertilization (dpf). Our data showed that the acute toxicity of PFHxS was much lower than PFOS, with a lethal concentration 50% of 508.11 ± 88.54 μM at 120 hpf. Low-dose PFHxS exposure significantly altered heart rates, blood flow, and swimming behavior in zebrafish larvae, suggesting potential cardiotoxicity and neurotoxicity of zebrafish. Data from transgenic zebrafish with specifically labeled hearts (CZ40) confirmed that PFHxS affects cardiovascular system development. PFHxS-induced changes in transgenic zebrafish with labeled liver and pancreas (CZ16) suggest that PFHxS may cause metabolic disorders and contribute to developmental defects. Gene expression analysis showed that PFHxS with potential estrogenic effect might also affect the gonadal development of zebrafish. Our study can offer an insight into the toxicity of PFHxS in aquatic environment and health risks of early-stage PFHxS exposure in humans.