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Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations

Early life exposure to adverse environments affects cardiovascular and metabolic systems in the offspring. These programmed effects are transmissible to a second generation through both male and female lines, suggesting germline transmission. We have previously shown that prenatal overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces birth weight in the first generation (F1), a phenotype which is transmitted to a second generation (F2), particularly through the male line. | Cartier et al. Genome Biology 2018 19 50 https doi.org 10.1186 s13059-018-1422-4 RESEARCH ARTICLE Open Access Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations Jessy Cartier1 Thomas Smith2 John P. Thomson3 Catherine M. Rose1 Batbayar Khulan1 Andreas Heger2 Richard R. Meehan3 and Amanda J. Drake1 Abstract Background Early life exposure to adverse environments affects cardiovascular and metabolic systems in the offspring. These programmed effects are transmissible to a second generation through both male and female lines suggesting germline transmission. We have previously shown that prenatal overexposure to the synthetic glucocorticoid dexamethasone Dex in rats reduces birth weight in the first generation F1 a phenotype which is transmitted to a second generation F2 particularly through the male line. We hypothesize that Dex exposure affects developing germ cells resulting in transmissible alterations in DNA methylation histone marks and or small RNA in the male germline. Results We profile epigenetic marks in sperm from F1 Sprague Dawley rats expressing a germ cell-specific GFP transgene following Dex or vehicle treatment of the mothers using methylated DNA immunoprecipitation sequencing small RNA sequencing and chromatin immunoprecipitation sequencing for H3K4me3 H3K4me1 H3K27me3 and H3K9me3. Although effects on birth weight are transmitted to the F2 generation through the male line no differences in DNA methylation histone modifications or small RNA were detected between germ cells and sperm from Dex-exposed animals and controls. Conclusions Although the phenotype is transmitted to a second generation we are unable to detect specific changes in DNA methylation common histone modifications or small RNA profiles in sperm. Dex exposure is associated with more variable 5mC levels particularly at non-promoter loci. Although this could be one mechanism contributing to the observed .