Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

Journal Article · Tue Dec 01 00:00:00 EST 2015 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2015.09.024· OSTI ID:22687825

Ma, Jing; Chen, Xi; Liu, Yanan ^[1]; Xie, Qunhui ^[2]; Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan ^[1]; Zhao, Bin ^[2]; Tang, Naijun ^[1]

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1. Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China)
2. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

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. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.

• OSTI ID: 22687825
• Journal Information: Toxicology and Applied Pharmacology, Vol. 289, Issue 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINES
AMINOTRANSFERASES
ANIMAL TISSUES
AROMATICS
CHAIN REACTIONS
DIOXIN
DMSO
DNA
GENES
GROWTH FACTORS
INSULIN
INTAKE
ION CYCLOTRON-RESONANCE
LIVER
METHYL TRANSFERASES
METHYLATION
OXIDOREDUCTASES
PHENOTYPE
PHOSPHATES
POLYMERASE CHAIN REACTION
POLYMERASES
PROGENY
RATS
RECEPTORS
TOXICITY