دورية أكاديمية
Transcriptional pathways linked to fetal and maternal hepatic dysfunction caused by gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice.
العنوان: | Transcriptional pathways linked to fetal and maternal hepatic dysfunction caused by gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice. |
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المؤلفون: | Blake BE; Chemical and Pollutant Assessment Division, Center for Public Health and Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA; Mechanistic Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: blake.bevin@epa.gov., Miller CN; Cardiopulmonary Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA., Nguyen H; Oak Ridge Institute for Science and Education, Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, NC, USA., Chappell VA; Mechanistic Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Phan TP; Mechanistic Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Phadke DP; Sciome LLC, Research Triangle Park, NC, USA., Balik-Meisner MR; Sciome LLC, Research Triangle Park, NC, USA., Mav D; Sciome LLC, Research Triangle Park, NC, USA., Shah RR; Sciome LLC, Research Triangle Park, NC, USA., Fenton SE; Mechanistic Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. |
المصدر: | Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2022 Dec 15; Vol. 248, pp. 114314. Date of Electronic Publication: 2022 Nov 24. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7805381 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2414 (Electronic) Linking ISSN: 01476513 NLM ISO Abbreviation: Ecotoxicol Environ Saf Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Amsterdam, Netherlands : Elsevier |
مواضيع طبية MeSH: | Fluorocarbons*/toxicity, Adult ; Humans ; Female ; Pregnancy ; Mice ; Animals ; Oxides ; Caprylates/toxicity ; Fetus ; Polymers |
مستخلص: | Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, and fire-fighting foams which have become environmental pollutants of concern due to their persistence, ubiquity, and associations with adverse human health outcomes, including in pregnant persons and their offspring. Multiple PFAS are associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver are not fully described. Here we performed transcriptomic analyses in the mouse to investigate the molecular mechanisms of hepatic toxicity in the dam and its fetus after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, known as GenX). Pregnant CD-1 mice were exposed via oral gavage from embryonic day (E) 1.5-17.5 to PFOA (0, 1, or 5 mg/kg-d) or GenX (0, 2, or 10 mg/kg-d). Maternal and fetal liver RNA was isolated (N = 5 per dose/group) and the transcriptome analyzed by Affymetrix Array. Differentially expressed genes (DEG) and differentially enriched pathways (DEP) were obtained. DEG patterns were similar in maternal liver for 5 mg/kg PFOA, 2 mg/kg GenX, and 10 mg/kg GenX (R 2 : 0.46-0.66). DEG patterns were similar across all 4 dose groups in fetal liver (R 2 : 0.59-0.81). There were more DEGs in fetal liver compared to maternal liver at the low doses for both PFOA (fetal = 69, maternal = 8) and GenX (fetal = 154, maternal = 93). Upregulated DEPs identified across all groups included Fatty Acid Metabolism, Peroxisome, Oxidative Phosphorylation, Adipogenesis, and Bile Acid Metabolism. Transcriptome-phenotype correlation analyses demonstrated > 1000 maternal liver DEGs were significantly correlated with maternal relative liver weight (R 2 >0.92). These findings show shared biological pathways of liver toxicity for PFOA and GenX in maternal and fetal livers in CD-1 mice. The limited overlap in specific DEGs between the dam and fetus suggests the developing liver responds differently than the adult liver to these chemical stressors. This work helps define mechanisms of hepatic toxicity of two structurally unique PFAS and may help predict latent consequences of developmental exposure. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Published by Elsevier Inc.) |
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معلومات مُعتمدة: | T32 ES007126 United States ES NIEHS NIH HHS; ZIA ES102785 United States ImNIH Intramural NIH HHS |
فهرسة مساهمة: | Keywords: Animal models; Developmental exposure; Emerging contaminants; Liver disease; PFAS |
المشرفين على المادة: | 947VD76D3L (perfluorooctanoic acid) 0 (Fluorocarbons) 0 (Oxides) 0 (Caprylates) 0 (Polymers) |
تواريخ الأحداث: | Date Created: 20221127 Date Completed: 20221206 Latest Revision: 20240216 |
رمز التحديث: | 20240216 |
مُعرف محوري في PubMed: | PMC9742811 |
DOI: | 10.1016/j.ecoenv.2022.114314 |
PMID: | 36436258 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1090-2414 |
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DOI: | 10.1016/j.ecoenv.2022.114314 |