Department of Environmental Health Sciences, School of Public Health & Health Sciences, University of Massachusetts Amherst, 686 North Pleasant Street, Amherst, MA 01003, USA.
Department of Biostatistics & Epidemiology, School of Public Health & Health Sciences, University of Massachusetts Amherst, 715 North Pleasant Street, Amherst, MA 01002, USA.
Epigenomics. 2020 Dec;12(24):2141-2153. doi: 10.2217/epi-2020-0253. Epub 2020 Dec 15.
Accumulating evidence associates sperm mitochondria DNA copy number (mtDNAcn) with male infertility and reproductive success. However, the mechanism underlying mtDNAcn variation is largely unknown. Sperm mtDNAcn and genome-wide DNA methylation were assessed using triplex probe-based quantitative PCR and Illumina's 450K array, respectively. Multivariable models assessed the association between sperm mtDNAcn and DNA methylation profiles of 47 men seeking infertility treatment. candidate-gene approach showed sperm mtDNAcn was associated with 16 CpGs located at/near and genes. Unbiased genome-wide analysis revealed that sperm mtDNAcn was associated with 218 sperm differentially methylated regions (q < 0.05), which displayed predominantly (94%) increases in methylation. Findings suggest that DNA methylation may play a role in regulating sperm mtDNAcn.
越来越多的证据表明精子线粒体 DNA 拷贝数 (mtDNAcn) 与男性不育和生殖成功有关。然而，mtDNAcn 变异的机制在很大程度上尚不清楚。使用三探针定量 PCR 和 Illumina 的 450K 阵列分别评估精子 mtDNAcn 和全基因组 DNA 甲基化。多变量模型评估了 47 名寻求不孕治疗的男性的精子 mtDNAcn 与 DNA 甲基化图谱之间的关联。候选基因方法表明，精子 mtDNAcn 与位于/附近的 16 个 CpG 以及 个基因有关。无偏全基因组分析显示，精子 mtDNAcn 与 218 个精子差异甲基化区域（q<0.05）相关，这些区域的甲基化主要增加（94%）。这些发现表明，DNA 甲基化可能在调节精子 mtDNAcn 中发挥作用。
