Age-related and species-specific methylation changes in the protein-coding marmoset sperm epigenome.

Autor: Dittrich M; Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.; Department of Bioinformatics, Julius Maximilians University, Würzburg, Germany., Bernhardt L; Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany., Penfold CA; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK., Boroviak TE; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Drummer C; Platform Degenerative Diseases, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Göttingen, Germany., Behr R; Platform Degenerative Diseases, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Göttingen, Germany., Müller T; Department of Bioinformatics, Julius Maximilians University, Würzburg, Germany., Haaf T; Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Aug; Vol. 23 (8), pp. e14200. Date of Electronic Publication: 2024 May 16.
DOI: 10.1111/acel.14200
Abstrakt: The sperm epigenome is thought to affect the developmental programming of the resulting embryo, influencing health and disease in later life. Age-related methylation changes in the sperm of old fathers may mediate the increased risks for reproductive and offspring medical problems. The impact of paternal age on sperm methylation has been extensively studied in humans and, to a lesser extent, in rodents and cattle. Here, we performed a comparative analysis of paternal age effects on protein-coding genes in the human and marmoset sperm methylomes. The marmoset has gained growing importance as a non-human primate model of aging and age-related diseases. Using reduced representation bisulfite sequencing, we identified age-related differentially methylated transcription start site (ageTSS) regions in 204 marmoset and 27 human genes. The direction of methylation changes was the opposite, increasing with age in marmosets and decreasing in humans. None of the identified ageTSS was differentially methylated in both species. Although the average methylation levels of all TSS regions were highly correlated between marmosets and humans, with the majority of TSS being hypomethylated in sperm, more than 300 protein-coding genes were endowed with species-specifically (hypo)methylated TSS. Several genes of the glycosphingolipid (GSL) biosynthesis pathway, which plays a role in embryonic stem cell differentiation and regulation of development, were hypomethylated (<5%) in human and fully methylated (>95%) in marmoset sperm. The expression levels and patterns of defined sets of GSL genes differed considerably between human and marmoset pre-implantation embryo stages and blastocyst tissues, respectively.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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