Physiological and transcriptomic effects of hexafluoropropylene oxide dimer acid in Caenorhabditis elegans during development

Per- and polyfluoroalkyl substances (PFAS) are chemicals resistant to degradation. While such a feature is desirable in consumer and industrial products, some PFAS, including perfluorooctanoic acid (PFOA), are toxic and bioaccumulate. Hexafluoropropylene oxide dimer acid (HFPO-DA), an emerging PFAS developed to replace PFOA, has not been extensively studied. To evaluate the potential toxicity of HFPO-DA with a cost- and time-efficient approach, we exposed C. elegans larvae for 48 h to 4 × 10-9-4 g/L HFPO-DA in liquid media and measured developmental, behavioral, locomotor, and transcriptional effects at various exposure levels. Worms exposed to 1.5-4 g/L HFPO-DA were developmentally delayed, and progeny production was significantly delayed (p < 0.05) in worms exposed to 2-4 g/L HFPO-DA. Statistically significant differential gene expression was identified in all fourteen HFPO-DA exposure groups ranging from 1.25 × 10-5 to 4 g/L, except for 6.25 × 10-5 g/L. Among 10298 analyzed genes, 2624 differentially expressed genes (DEGs) were identified in the developmentally delayed 4 g/L group only, and 78 genes were differentially expressed in at least one of the thirteen groups testing 1.25 × 10-5-2 g/L HFPO-DA exposures. Genes encoding for detoxification enzymes including cytochrome P450 and UDP glucuronosyltransferases were upregulated in 0.25-4 g/L acute exposure groups. DEGs were also identified in lower exposure level groups, though they did not share biological functions except for six ribosomal protein-coding genes. While our transcriptional data is inconclusive to infer mechanisms of toxicity, the significant gene expression differences at 1.25 × 10-5 g/L, the lowest concentration tested for transcriptional changes, calls for further targeted analyses of low-dose HFPO-DA exposure effects.