Assessment of the Mode of Action Underlying the Effects of GenX in Mouse Liver and Implications for Assessing Human Health Risks

To investigate the potential role of peroxisome proliferator activated receptor–alpha (PPARa) activation in mice, RNA sequencing was conducted on paraffin-embedded liver sections from a 90-day toxicity study of GenX conducted in mice. the TempO-Seq platform was utilized for RNA sequencing data collection. Differentially expressed genes were identified for each treatment group, and gene set enrichment analysis was conducted using gene sets that represent biological processes and known canonical pathways. Significant enrichment of peroxisome signaling was evident in males and females exposed to 0.5 and 5 mg/kg GenX, with no enrichment at 0.1 mg/kg. PPAR signaling and fatty acid metabolism were among the most significantly enriched gene sets, and two gene sets specific to the PPARa subtype were also significantly enriched. Examination of whole transcriptome expression by targeted sequencing in liver tissue from male and female mice treated with varying concentrations of ammonium 2,3,3,3-tetrafluro-2-(heptafluoropropoxy)-propanoate (CASRN 62037-80-3, "GenX").