NDLI: Genome-wide analysis of epigenetic changes in mouse sperm by maternal exposure to endocrine disruptor vinclozolin

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Genome-wide analysis of epigenetic changes in mouse sperm by maternal exposure to endocrine disruptor vinclozolin

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Molecular & Cellular Toxicology : Volume 7

Molecular & Cellular Toxicology : Volume 6

Genome-wide analysis of epigenetic changes in mouse sperm by maternal exposure to endocrine disruptor vinclozolin

Content Provider	Springer Nature Link
Author	Lee, Seung Hoon Oh, TaeJeong
Copyright Year	2012
Abstract	The genome-wide epigenetic alterations (DNA methylation) in germ cells have not been extensively studied in mice by exposure to environmental hazards. We first report here that a genome-wide analysis of CpG methylation in F1 mice sperm by maternal exposure to the anti-androgenic compound vinclozolin (VCZ). The gestated (GD) female mice (n=8) were injected intraperitoneally with VCZ (100 mg/kg/day), from GD 8 to GD 15 to induce reproductive toxicity and epigenetic alterations in mice. Our observations showed a loss of normal spermatogenesis and abnormal seminiferous tubule morphology in VCZ-treated F1 males. We also confirmed reduced fertility of the VCZ-exposed F1 male mice and increased abnormality in F2 fetuses. We compared the methylation patterns of five untreated with 13 VCZ-treated F1 mice male via high-resolution CpG microarray analysis to determine CpG methylation alterations in F1 male sperm DNA. The overall methylation between control and treated F1 sperm showed normal distribution, and differentially methylated CpG islands were frequently mapped between the −0.5 kb and +1.0 kb regions of the transcription start site (TSS). We identified more than several hundred epigenetically altered genes by statistical analysis (P<0.05). More than 50% of the statistically significantly methylated loci were also mapped at the vicinity of TSS. We further examined the effects of VCZ on the mouse repeated elements and paternally imprinted genes. VCZ induced no epigenetic alterations in repeated mouse elements (LINE and B1) and the paternally imprinted Dlk1 gene, whereas it did affect the paternally imprinted H19 gene. In conclusion, we successfully explored VCZ-induced genome-wide epigenetic changes on F1 mice sperm DNA by global methylation profiling, and our data will provide important clues for studying the epigenetic changes of germ cells due to exposure to environmental hazards.
Starting Page	43
Ending Page	52
Page Count	10
File Format	PDF
ISSN	1738642X
Journal	Molecular & Cellular Toxicology
Volume Number	8
Issue Number	1
e-ISSN	20928467
Language	English
Publisher	The Korean Society of Toxicogenomics and Toxicoproteomics
Publisher Date	2012-04-04
Publisher Place	Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Epigenetic change Endocrine disruptor Vinclozolin Male reproduction Pharmacology/Toxicology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Public Health, Environmental and Occupational Health Toxicology Pathology and Forensic Medicine

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