title: Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs.
abstract: Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8-14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Qunhui
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: binzhao@rcees.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China. Electronic address: tangnaijun@tijmu.edu.cn.
authors.forename: Naijun
authors.initials: N
authors.lastname: Tang
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018392:Genomic Imprinting / Q000187:drug effects*; D040941:Heredity; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D009929:Organ Size; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D007335:Insulin-Like Growth Factor II; D000072317:Polychlorinated Dibenzodioxins; D000097584:DNA Methyltransferase 3B; C000599313:Igf2 protein, rat; C000619382:Dnmt1 protein, rat
keywords: 2,3,7,8-Tetrachlorodibenzo-p-Dioxin; DNA methyltransferase; Differentially methylated region; Epigenetic transgenerational inheritance; Imprinted gene; Somatic tissue