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CC BY V4.0, Open Access
Journal article
Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome
PloS one, Vol.5(9), pp.1-17
09/30/2010
Handle:
https://hdl.handle.net/2376/107405
PMCID: PMC2948035
PMID: 20927350
Abstract
Previous observations have demonstrated that embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes transgenerational adult onset disease such as male infertility, kidney disease, prostate disease, immune abnormalities and tumor development. The current study investigates genome-wide promoter DNA methylation alterations in the sperm of F3 generation rats whose F0 generation mother was exposed to vinclozolin. A methylated DNA immunoprecipitation with methyl-cytosine antibody followed by a promoter tilling microarray (MeDIP-Chip) procedure was used to identify 52 different regions with statistically significant altered methylation in the sperm promoter epigenome. Mass spectrometry bisulfite analysis was used to map the CpG DNA methylation and 16 differential DNA methylation regions were confirmed, while the remainder could not be analyzed due to bisulfite technical limitations. Analysis of these validated regions identified a consensus DNA sequence (motif) that associated with 75% of the promoters. Interestingly, only 16.8% of a random set of 125 promoters contained this motif. One candidate promoter (Fam111a) was found to be due to a copy number variation (CNV) and not a methylation change, suggesting initial alterations in the germline epigenome may promote genetic abnormalities such as induced CNV in later generations. This study identifies differential DNA methylation sites in promoter regions three generations after the initial exposure and identifies common genome features present in these regions. In addition to primary epimutations, a potential indirect genetic abnormality was identified, and both are postulated to be involved in the epigenetic transgenerational inheritance observed. This study confirms that an environmental agent has the ability to induce epigenetic transgenerational changes in the sperm epigenome.
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Details
- Title
- Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome
- Creators
- Carlos Guerrero-Bosagna - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of AmericaMatthew SettlesBen LuckerMichael K Skinner
- Publication Details
- PloS one, Vol.5(9), pp.1-17
- Academic Unit
- Biological Sciences, School of
- Publisher
- United States
- Grant note
- R01 ES012974-07 / NIEHS NIH HHS R01 ES012974 / NIEHS NIH HHS
- Identifiers
- 99900547006301842
- Language
- English
- Resource Type
- Journal article