Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm
| Autor: | Christelle Stouder, Ariane Paoloni-Giacobino |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Embryology Oxazoles/toxicity Tail/metabolism Endocrine Disruptors Endocrine Disruptors/toxicity Mice chemistry.chemical_compound Endocrinology Androgen Antagonists/toxicity Pregnancy ddc:576.5 Vinclozolin Imprinting (psychology) Genomic Imprinting/drug effects Oxazoles Sperm motility Sperm Count Reproduction Obstetrics and Gynecology DNA Methylation/drug effects Spermatozoa Phenotype Reproduction/drug effects/genetics Liver Prenatal Exposure Delayed Effects Proteins/genetics DNA methylation Sperm Motility Muscle Long Noncoding Female RNA Long Noncoding Liver/metabolism Spermatogenesis/drug effects/genetics Tail medicine.medical_specialty Spermatozoa/drug effects/metabolism/pathology Genotype Offspring Kruppel-Like Transcription Factors CpG Islands/drug effects Skeletal/metabolism Biology snRNP Core Proteins Genomic Imprinting Internal medicine medicine Animals Muscle Skeletal Spermatogenesis Kruppel-Like Transcription Factors/genetics Proteins Androgen Antagonists Cell Biology DNA Methylation Sperm Reproductive Medicine chemistry SnRNP Core Proteins/genetics RNA CpG Islands Genomic imprinting |
| Zdroj: | Reproduction, Vol. 139, No 2 (2010) pp. 373-379 |
| ISSN: | 1741-7899 1470-1626 |
| DOI: | 10.1530/rep-09-0340 |
| Popis: | Endocrine-disrupting chemicals (EDCs), among which is the antiandrogen vinclozolin (VCZ), have been reported to affect the male reproductive system. In this study, VCZ was administered to pregnant mice at the time of embryo sex determination, and its possible effects on the differentially methylated domains (DMDs) of two paternally (H19andGtl2) and three maternally (Peg1,Snrpn, andPeg3) imprinted genes were tested in the male offspring. The CpGs methylation status within the five gene DMDs was analyzed in the sperm, tail, liver, and skeletal muscle DNAs by pyrosequencing. In the sperm of controls, the percentages of methylated CpGs were close to the theoretical values of 100 and 0% in paternally or maternally imprinted genes respectively. VCZ decreased the percentages of methylated CpGs ofH19andGtl2(respective values 83.1 and 91.5%) and increased those ofPeg1,Snrpn, andPeg3(respective values 11.3, 18.3, and 11.2%). The effects of VCZ were transgenerational, but they disappeared gradually from F1 to F3. The mean sperm concentration of the VCZ-administered female offspring was only 56% of that of the controls in the F1 offspring, and it was back to normal values in the F2 and F3 offspring. In the somatic cells of controls, the percentages of methylated CpGs were close to the theoretical value of 50% and, surprisingly, VCZ altered the methylation ofPeg3. We propose that the deleterious effects of VCZ on the male reproductive system are mediated by imprinting defects in the sperm. The reported effects of EDCs on human male spermatogenesis might be mediated by analogous imprinting alterations. |
| Databáze: | OpenAIRE |
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