ArticleFrontiers in toxicology2022
Evaluation of Transcriptomic Responses in Livers of Mice Exposed to the Short-Chain PFAS Compound HFPO-DA.
Article in Frontiers in toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Exposure Duration Shapes the Hepatic Response to GenX: Divergent Acute and Chronic Transcriptomic Profiles Reveal Non-Monotonic Dose Effects and Increased Sensitivity in Human Liver Spheroids.bioRxiv : the preprint server for biology · 2026Article
- Integration of mechanistic and repeat dose toxicity data in the derivation of an oral reference dose for HFPO-DA.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Article
- Perfluoroalkyl Substances (PFAS) and Lipid Metabolism in Experimental Animal Models: A Scoping Review on the Mechanisms Behind the Induced Hepatotoxicity.Current issues in molecular biology · 2025Review
- Visceral, Neural, and Immunotoxicity of Per- and Polyfluoroalkyl Substances: A Mini Review.Toxics · 2025Review
- Comparison of phenotypic and transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and Ppara-null mouse livers.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Placental PFAS concentrations are associated with perturbations of placental DNA methylation.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes.Environmental science & technology · 2024Article
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Article
- Investigation of Peroxisome Proliferator-Activated Receptor Genes as Requirements for Visual Startle Response Hyperactivity in Larval Zebrafish Exposed to Structurally Similar Per- and Polyfluoroalkyl Substances (PFAS).Environmental health perspectives · 2024Article
- Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and PPARα knockout mouse hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in mouse, rat, and pooled human hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Involvement of per- and polyfluoroalkyl compounds in tumor development.Archives of toxicology · 2024Review
- Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis.Frontiers in toxicology · 2024Article
- Article
- Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.Toxicologic pathology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HFPO-DA (ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; CASRN 62037-80-3) is a component of the GenX technology platform used as a polymerization aid in the manufacture of some types of fluoropolymers. The liver is the primary target of toxicity for HFPO-DA in rodents and previous examination of hepatic transcriptomic responses in mice following oral exposure to HFPO-DA for 90 days showed induction of peroxisome proliferator-activated receptor signaling pathways, predominantly by PPARα, as well as increased gene expression of both peroxisomal and mitochondrial fatty acid metabolism. To further investigate the mechanism of liver toxicity, transcriptomic analysis was conducted on liver tissue from mice orally exposed to 0, 0.1, 0.5 or 5 mg/kg-bw/day HFPO-DA in a reproduction/developmental toxicity study. Hepatic gene expression changes demonstrated activation of the PPARα signaling pathway. Peroxisomal and mitochondrial fatty acid β-oxidation gene sets were enriched at lower HFPO-DA concentrations, and complement cascade, cell cycle and apoptosis related gene sets were enriched at higher HFPO-DA concentrations. These results support the reported histopathological findings in livers of mice from this study and indicate that the effects of HFPO-DA are mediated through rodent-specific PPARα signaling mechanisms regardless of reproductive status in mice.
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