Institute of Human Genetics, Julius Maximilians University, 97074 Würzburg, Germany.
Department of Bioinformatics, Julius Maximilians University, 97074 Würzburg, Germany.
Cells. 2022 Feb 19;11(4):731. doi: 10.3390/cells11040731.
A growing number of sperm methylome analyses have identified genomic loci that are susceptible to paternal age effects in a variety of mammalian species, including human, bovine, and mouse. However, there is little overlap between different data sets. Here, we studied whether or not paternal age effects on the sperm epigenome have been conserved in mammalian evolution and compared methylation patterns of orthologous regulatory regions (mainly gene promoters) containing both conserved and non-conserved CpG sites in 94 human, 36 bovine, and 94 mouse sperm samples, using bisulfite pyrosequencing. We discovered three (, , and ) age-related differentially methylated regions (ageDMRs) in humans, four (, , , and ) in bovines, and three (, , and ) in mice. Remarkably, the identified sperm ageDMRs were all species-specific. Most ageDMRs were in genomic regions with medium methylation levels and large methylation variation. Orthologous regions in species not showing this age effect were either hypermethylated (>80%) or hypomethylated (<20%). In humans and mice, ageDMRs lost methylation, whereas bovine ageDMRs gained methylation with age. Our results are in line with the hypothesis that sperm ageDMRs are in regions under epigenomic evolution and may be part of an epigenetic mechanism(s) for lineage-specific environmental adaptations and provide a solid basis for studies on downstream effects in the genes analyzed here.
越来越多的精子甲基化组分析已经确定了在多种哺乳动物物种（包括人类、牛和鼠）中易受父本年龄影响的基因组位点。然而，不同数据集之间几乎没有重叠。在这里，我们研究了父本年龄对精子表观基因组的影响是否在哺乳动物进化中得到了保守，并比较了 94 个人类、36 个牛和 94 个鼠标精子样本中含有保守和非保守 CpG 位点的同源调控区（主要是基因启动子）的甲基化模式，使用亚硫酸氢盐焦磷酸测序。我们在人类中发现了三个（、和）与年龄相关的差异甲基化区域（ageDMRs），在牛中发现了四个（、、和），在老鼠中发现了三个（、和）。值得注意的是，鉴定出的精子 ageDMRs 都是物种特异性的。大多数 ageDMRs 位于甲基化水平中等且甲基化变化较大的基因组区域。在没有表现出这种年龄效应的物种中，同源区域要么高度甲基化（>80%），要么低甲基化（<20%）。在人类和老鼠中，ageDMRs 失去了甲基化，而牛的 ageDMRs 随着年龄的增长获得了甲基化。我们的结果与精子 ageDMRs 位于表观基因组进化区域的假设一致，并且可能是种系特异性环境适应的表观遗传机制的一部分，并为在这里分析的基因的下游效应研究提供了坚实的基础。
