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Perfluorooctanoic acid (PFOA) is frequently detected in the environment and accumulates in amphibians such as black-spotted frogs (Rana nigromaculata) with toxic effects; however, the mechanism underlying this toxicity is unclear. In this study, male black-spotted frogs were exposed to 10 μg/L waterborne PFOA for 21 days. Subsequently, the effect of PFOA exposure on gene expression in liver tissue was investigated using transcriptomic techniques. In total, 754 differentially expressed genes (DEGs; 389 up-regulated and 365 down-regulated) were identified. According to Kyoto Encyclopedia of Genes and Genomes enrichment and Gene Ontology functional enrichment analyses, the DEGs were mainly involved in lipid metabolism, endocrine functions, and immunity. Quantitative real-time polymerase chain reaction analysis of 15 selected DEGs revealed a high correlation (R2 = 0.9917) with the transcriptomic results. These results indicated that the PFOA hepatotoxicity in frogs is mediated mainly by lipid metabolism dysregulation, endocrine system disruption, and immunotoxicity. This study provides insights into the hepatotoxic mechanism of PFOA and other perfluorinated compounds in amphibians.

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