{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:26:13Z","timestamp":1791977173664,"version":"4.4.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>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\u00a0days showed induction of peroxisome proliferator-activated receptor signaling pathways, predominantly by PPAR\u03b1, 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\u00a0mg\/kg-bw\/day HFPO-DA in a reproduction\/developmental toxicity study. Hepatic gene expression changes demonstrated activation of the PPAR\u03b1 signaling pathway. Peroxisomal and mitochondrial fatty acid \u03b2-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 PPAR\u03b1 signaling mechanisms regardless of reproductive status in mice.<\/jats:p>","DOI":"10.3389\/ftox.2022.937168","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T02:22:06Z","timestamp":1656296526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Evaluation of Transcriptomic Responses in Livers of Mice Exposed to the Short-Chain PFAS Compound HFPO-DA"],"prefix":"10.3389","volume":"4","author":[{"given":"Melissa M.","family":"Heintz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A.","family":"Chappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie C.","family":"Haws","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5678","DOI":"10.1074\/jbc.273.10.5678","article-title":"Altered Constitutive Expression of Fatty Acid-Metabolizing Enzymes in Mice Lacking the Peroxisome Proliferator-Activated Receptor \u03b1 (PPAR\u03b1)","volume":"273","author":"Aoyama","year":"1998","journal-title":"J. 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