Cardiotoxicity of PFOA, PFOS, and PFOSA in Early Life Stage Zebrafish: Molecular Changes to Behavioral-level Response

The widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) globally has led to increased pol- lution in the environment and has subsequently posed health risks. Perfluorooctanoic acid (PFOA), perfluorooc- tanesulfonic acid (PFOS), and perfluorooctanesulfonamide (PFOSA) has been reported to induce immunotoxicity, endocrine toxicity, and developmental toxicity. However, the associated mechanisms and induction of cardiotox- icity following PFASs exposure remains poorly understood. Here, we explored the cardiac toxicity and associated mechanism in zebrafish embryos after exposure to PFOA, PFOS, and PFOSA at 1 and 10 𝜇g/L by RNA sequencing, morphological and physiological assessment, and behavioral alterations. Ingenuity Pathway Analysis (IPA) was used to predict disease and functions following exposure and predicted that the cardiac system was significantly affected by these three PFASs. The upregulation of miR-16–5p was predicted to act as an upstream regulator and involved in PFAS-induced pericardial edema. Cardiac output, an abnormal cardiac morphology, and atrial natriuretic peptide content were significantly altered following PFASs exposure. Furthermore, behavioral-level alterations were seen following exposure to PFASs. Our results indicated that PFASs could induce cardiotoxicity in zebrafish during early life stage development, the toxicity of PFOA and PFOSA may induce a more severe response relative to PFOS at relatively high concentrations according to the PCA analysis of all the tested data.