Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations
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 prenata...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Genome Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s13059-018-1422-4 |
| _version_ | 1818540841822584832 |
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| author | Jessy Cartier Thomas Smith John P. Thomson Catherine M. Rose Batbayar Khulan Andreas Heger Richard R. Meehan Amanda J. Drake |
| author_facet | Jessy Cartier Thomas Smith John P. Thomson Catherine M. Rose Batbayar Khulan Andreas Heger Richard R. Meehan Amanda J. Drake |
| author_sort | Jessy Cartier |
| collection | DOAJ |
| description | 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 phenotype, other germline epigenetic modifications or non-epigenetic mechanisms may be responsible for the transmission of programmed effects across generations in this model. |
| first_indexed | 2024-12-11T22:00:41Z |
| format | Article |
| id | doaj.art-6c306276f54543a09f131f709ef97c90 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-11T22:00:41Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-6c306276f54543a09f131f709ef97c902022-12-22T00:49:07ZengBMCGenome Biology1474-760X2018-04-0119111510.1186/s13059-018-1422-4Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generationsJessy Cartier0Thomas Smith1John P. Thomson2Catherine M. Rose3Batbayar Khulan4Andreas Heger5Richard R. Meehan6Amanda J. Drake7University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research InstituteMRC Computational Genomics Analysis and Training Programme, University of Oxford, MRC WIMM Centre for Computational Biology, The Weatherall Institute of Molecular Medicine, John Radcliffe HospitalMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of EdinburghUniversity/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research InstituteUniversity/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research InstituteMRC Computational Genomics Analysis and Training Programme, University of Oxford, MRC WIMM Centre for Computational Biology, The Weatherall Institute of Molecular Medicine, John Radcliffe HospitalMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of EdinburghUniversity/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research InstituteAbstract 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 phenotype, other germline epigenetic modifications or non-epigenetic mechanisms may be responsible for the transmission of programmed effects across generations in this model.http://link.springer.com/article/10.1186/s13059-018-1422-4Early life programmingDNA methylationHistone modificationsSmall RNAEpigeneticGermline transmission |
| spellingShingle | Jessy Cartier Thomas Smith John P. Thomson Catherine M. Rose Batbayar Khulan Andreas Heger Richard R. Meehan Amanda J. Drake Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations Genome Biology Early life programming DNA methylation Histone modifications Small RNA Epigenetic Germline transmission |
| title | Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations |
| title_full | Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations |
| title_fullStr | Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations |
| title_full_unstemmed | Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations |
| title_short | Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations |
| title_sort | investigation into the role of the germline epigenome in the transmission of glucocorticoid programmed effects across generations |
| topic | Early life programming DNA methylation Histone modifications Small RNA Epigenetic Germline transmission |
| url | http://link.springer.com/article/10.1186/s13059-018-1422-4 |
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