Differential Toxicity of Perfluorooctane Sulfonate (PFOS) in Wild-Type and Oatp1d1 Mutant Zebrafish Embryos

Abstract

ABSTRACTThis study presents a comprehensive analysis of the effects of perfluorooctane sulfonate (PFOS) exposure on zebrafish embryos, focusing on the differential responses between wild-type (WT) and oatp1d1 mutant embryos. The findings improve our understanding of the toxicokinetic and toxicodynamic mechanisms of PFOS, a persistent and bioaccumulative member of the per- and polyfluoroalkyl substances (PFAS) family. The study revealed significant differences in mortality rates with calculated LC50 values of 23.57 µM for WT and 16.71 µM for oatp1d1 mutants, indicating a higher susceptibility of the mutants to PFOS toxicity. This indicates the crucial role of the Oatp1d1 transporter in mediating the toxic effects of PFOS, possibly related to detoxification processes or regulation of bioavailability. Developmental abnormalities, particularly in the swim bladder, were more pronounced in mutant embryos, indicating the role of the transporter in mitigating PFOS-induced developmental toxicity. Gene expression analysis showed differential modulation of biotransformation genes, including cytochrome P450 (cyp) and glutathione S-transferase (gst) genes, underscoring the complexity of PFOS toxicity. The study also highlighted disruptions in lipid metabolism with altered expression of genes involved in lipid synthesis and oxidation, leading to abnormal lipid accumulation. These findings have significant implications for aquatic ecosystems and human health, as PFOS is persistent and bioaccumulative in the environment. The study emphasizes the need for stringent regulatory measures and effective remediation strategies to address PFOS contamination and protect both aquatic life and human populations.