{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:26:19Z","timestamp":1791977179250,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173474"],"award-info":[{"award-number":["82173474"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024A1515010708"],"award-info":[{"award-number":["2024A1515010708"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2025A04J7216"],"award-info":[{"award-number":["2025A04J7216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["82173474"],"award-info":[{"award-number":["82173474"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2024A1515010708"],"award-info":[{"award-number":["2024A1515010708"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2025A04J7216"],"award-info":[{"award-number":["2025A04J7216"]}]},{"name":"Science and Technology Program of Guangzhou","award":["82173474"],"award-info":[{"award-number":["82173474"]}]},{"name":"Science and Technology Program of Guangzhou","award":["2024A1515010708"],"award-info":[{"award-number":["2024A1515010708"]}]},{"name":"Science and Technology Program of Guangzhou","award":["2025A04J7216"],"award-info":[{"award-number":["2025A04J7216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Perfluorooctanoic acid (PFOA) and its replacement, GenX, are per- and polyfluoroalkyl substances (PFASs) widely used in industrial and consumer applications. Pregnant women are a vulnerable population to environmental pollutants. The maternal effects of GenX and PFOA exposure during pregnancy have not been fully elucidated. In this study, pregnant mice received daily oral doses of GenX (2 mg\/kg\/day), PFOA (1 mg\/kg\/day), or Milli-Q water (control) throughout gestation. Histopathological analyses revealed significant liver abnormalities in both exposure groups, including hepatocyte swelling, cellular disarray, eosinophilic degeneration, karyopyknosis, lipid vacuolation, and increased inflammatory responses. Through transcriptomics analyses, it was found that multiple metabolic and inflammatory pathways were enriched in both exposure groups. In the GenX group, overexpression of CYP4A, c-Myc, and Oatp2 proteins and decreased expression of EGFR and \u03b2-catenin in the liver suggested disruption of lipid and bile acid metabolism. In the PFOA group, significantly upregulated protein levels of NLRP3, GSDMD, caspase-1, IL-18, and IL-1\u03b2 indicated hepatic pyroptosis. Despite these distinct pathways, both compounds triggered inflammatory cytokine release in the liver, consistent with the results of the transcriptomics analysis, suggesting shared mechanisms of inflammatory liver injury. Taken together, our findings provided novel insights into the hepatotoxicity mechanisms of GenX and PFOA exposure during pregnancy, underscoring the potential health risks associated with PFAS exposure.<\/jats:p>","DOI":"10.3390\/toxics13080617","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gestational GenX Exposure Induces Maternal Hepatotoxicity by Disrupting the Lipid and Bile Acid Metabolism Distinguished from PFOA-Induced Pyroptosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Jin-Jin","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Kui","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1556-2167","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, No. 1838 North Guangzhou Road, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Muglia, L.J., Benhalima, K., Tong, S., and Ozanne, S. 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