Assessment of biological effects and the potential mode of action of per- and polyfluoroalkyl substances in developing zebrafish

Abstract

Per- and polyfluoroalkyl substances (PFAS) are widely used for consumer products. Some of PFAS have been listed as POPs due to their persistent and bioaccumulative natures, as well as toxicity. The present study aimed to evaluate the biological effects of representative PFAS and to understand the possible mode of action using developing zebrafish. Embryos exposed to perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) elicited pericardial and yolk-sac edemas and reduction of blood flow in trunk vessels at 96 hours post fertilization in concentration-dependent manner, with greater potency observed in PFOS than in PFHxS. The behavioral assay revealed that embryos exposed to PFOS increased motility without a major effect on swimbladder inflation, indicating hyperactivity. RNA-seq analysis showed that many differentially expressed genes (DEGs) were upregulated by both compounds, whereas a smaller number were the shared downregulated DEGs. Among DEGs are neuronal and behavioral pathways most highlighted in the enrichment analysis, which supports the behavioral disorder. We found that genes important for calcium metabolism, such as pth1a, pth2, and calca, were largely upregulated following exposure to both PFAS. These results, together with existing reports, suggest that behavioral disorders and possibly circulatory failure caused by PFAS exposure might occur through disruption of calcium signaling in developing zebrafish. We are underway to measure other endpoints to see if there is any association with transcriptomic changes caused by PFAS in zebrafish.