Global effects of identity and aging on the human sperm methylome.

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-08-07 DOI:10.1186/s13148-023-01541-6
Guilherme de Sena Brandine, Kenneth I Aston, Timothy G Jenkins, Andrew D Smith
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Abstract

Background: As the average age of fatherhood increases worldwide, so too does the need for understanding effects of aging in male germline cells. Molecular change, including epigenomic alterations, may impact offspring. Age-associated change to DNA cytosine methylation in the cytosine-guanine (CpG) context is a hallmark of aging tissues, including sperm. Prior studies have led to accurate models that predict a man's age based on specific methylation features in the DNA of sperm, but the relationship between aging and global DNA methylation in sperm remains opaque. Further clarification requires a more complete survey of the methylome with assessment of variability within and between individuals.

Results: We collected sperm methylome data in a longitudinal study of ten healthy fertile men. We used whole-genome bisulfite sequencing of samples collected 10 to 18 years apart from each donor. We found that, overall, variability between donors far exceeds age-associated variation. After controlling for donor identity, we see significant age-dependent genome-wide change to the methylome. Notably, trends of change with age depend on genomic location or annotation, with contrasting signatures that correlate with gene density and proximity to centromeres and promoter regions.

Conclusions: We uncovered epigenetic signatures that reflect a stable process which begins in early adulthood, progressing steadily through most of the male lifespan, and warrants consideration in any future study of the aging sperm epigenome.

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身份和衰老对人类精子甲基组的整体影响。
背景:随着世界范围内成为父亲的平均年龄的增加,对男性生殖细胞衰老影响的理解需求也在增加。分子变化,包括表观基因组的改变,可能会影响后代。在胞嘧啶-鸟嘌呤(CpG)背景下,与年龄相关的DNA胞嘧啶甲基化变化是衰老组织(包括精子)的标志。先前的研究已经建立了精确的模型,根据精子DNA的特定甲基化特征来预测男性的年龄,但衰老与精子中整体DNA甲基化之间的关系仍然不清楚。进一步的澄清需要对甲基组进行更全面的调查,并评估个体内部和个体之间的变异性。结果:我们收集了10名健康育龄男性的精子甲基组数据。我们对每个供体相隔10至18年收集的样本进行了全基因组亚硫酸盐测序。我们发现,总的来说,捐献者之间的差异远远超过了与年龄相关的差异。在控制供体身份后,我们看到甲基组显著的年龄依赖性全基因组变化。值得注意的是,随年龄变化的趋势取决于基因组位置或注释,与基因密度和与着丝粒和启动子区域的接近程度相关的对比特征。结论:我们发现的表观遗传特征反映了一个稳定的过程,该过程始于成年早期,在大多数男性寿命中稳步发展,值得在未来任何衰老精子表观基因组的研究中考虑。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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