title: RNA-sequencing analysis reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following exposure in mice.
abstract: The toxicological impact of traditional perfluoroalkyl chemicals has led to the elimination and restriction of these substances. However, many novel perfluoroalkyl alternatives remain unregulated and little is known about their potential effects on environmental and human health. Daily administration of two alternative perfluoroalkyl substances, HFPO2 and HFPO4 (1 mg kg-1body weight), for 28 days resulted in hepatomegaly and hepatic histopathological injury in mice, particularly in the HFPO4 group. We generated and compared high-throughput RNA-sequencing data from hepatic tissues in control and treatment group mice to clarify the mechanism of HFPO2 and HFPO4 hepatotoxicity. We identified 146 (101 upregulated, 45 downregulated) and 1295 (716 upregulated, 579 downregulated) hepatic transcripts that exhibited statistically significant changes (fold change ≥2 or ≤0.5, false discovery rate < 0.05) after HFPO2 and HFPO4 treatment, respectively. Among them, 111 (82 upregulated, 29 downregulated) transcripts were changed in both groups, and lipid metabolism associated genes were dominant. Thus, similar to their popular predecessors, HFPO2 and HFPO4 exposure exerted hepatic effects, including hepatomegaly and injury, and altered lipid metabolism gene levels in the liver, though HFPO4 exerted greater hepatotoxicity than HFPO2. The unregulated use of these emerging perfluoroalkyl alternatives may affect environmental and human health, and their biological effects need further exploration. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Ruina
authors.initials: R
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000085:Acetates / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D005466:Fluorocarbons / Q000633:toxicity*; D059014:High-Throughput Nucleotide Sequencing; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011422:Propionates / Q000633:toxicity; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017423:Sequence Analysis, RNA; D015533:Transcriptional Activation; D059467:Transcriptome / Q000235:genetics
chemical_list: D000085:Acetates; D005466:Fluorocarbons; C000625836:HFPO4 compound; D047495:PPAR gamma; D011422:Propionates; C000611729:ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; D012313:RNA; D003577:Cytochrome P-450 Enzyme System
keywords: HFPO2; HFPO4; Hepatotoxicity; PPAR; RNA-seq