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Title: Transmission of glucocorticoid-programmed effects occurs without detectable changes in the germline epigenome : Prenatal overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces birthweight in the first generation (F1) and second generation (F2), including through the male line. We hypothesised that the mechanism for this would likely be epigentic perturbations in the male germline. DNA methylation profiling of F1 male germ cells at E19.5 and small RNA expression and Chromatin Immunoprecipitation (ChIP) sequencing for H3K4me3, H3K27me3 and H3K9me3 on F1 sperm were used to test this hypothesis. No differences in DNA methylation, histone modifications or small RNA expression were observed, suggesting non-epigentic mechanisms may be responsible for the transmission of programmed effects in this model.      
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ID:
PRJEB14719
description:
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 birthweight in the first generation (F1) a phenotype which is transmitted to a second generation (F2), particularly through the male line. The male germline can transmit epigenetic marks to oocytes. Since the developing germ cells which form the F2 are also exposed to Dex, we hypothesised that this may result in transmissible alterations in DNA methylation, histone marks and/or small RNA in the male germline. Results: Primordial germ cells (PGC) undergo extensive epigenetic reprogramming including erasure and re-establishment of DNA methylation in late gestation. We isolated DNA from enriched E19.5 PGCs from F1 male embryos of Sprague Dawley rats expressing a germ cell specific GFP transgene (GCS-GFP) following Dex or Veh treatment of the mothers for DNA methylation profiling. Small RNA expression and Chromatin Immunoprecipitation (ChIP) sequencing for H3K4me3, H3K27me3 and H3K9me3 was performed on F1 sperm. Although effects on birthweight were transmitted to the F2 generation through the male line, there were no detectable differences in DNA methylation, histone modifications or small RNA between germ cells and sperm from Dex-exposed animals and controls. Conclusions: Our data suggest that mechanisms other than standard germline epigenetic modifications are responsible for the transmission of programmed effects across generations in this model.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJEB14719
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abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject