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Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2015 Dec 01; Vol. 289 (2), pp. 193-202. Date of Electronic Publication: 2015 Oct 09. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Chemical and Drug Induced Liver Injury metabolism
Chemical and Drug Induced Liver Injury pathology
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases genetics
DNA Methyltransferase 3A
Female
Gene Expression Regulation, Enzymologic
Heredity
Insulin-Like Growth Factor II metabolism
Liver metabolism
Liver pathology
Male
Organ Size
Pregnancy
Rats, Sprague-Dawley
DNA Methyltransferase 3B
Chemical and Drug Induced Liver Injury genetics
DNA (Cytosine-5-)-Methyltransferases metabolism
DNA Methylation drug effects
Epigenesis, Genetic drug effects
Genomic Imprinting drug effects
Insulin-Like Growth Factor II genetics
Liver drug effects
Maternal Exposure
Polychlorinated Dibenzodioxins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 289
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26455773
- Full Text :
- https://doi.org/10.1016/j.taap.2015.09.024