Department of Clinical Laboratory, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University (Nanjing General Hospital of Nanjing Military Region), Nanjing, China.
Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Andrologia. 2019 Jun;51(5):e13239. doi: 10.1111/and.13239. Epub 2019 Jan 24.
Abnormal imprinted genes methylation in spermatozoa has been shown to be associated with subfertility. However, the relationship between sperm DNA damage and specific imprinted genes methylation remains unclear. In this study, DNA methylation levels were determined at seven imprinted genes loci (H19, INS-IGF2, KCNQ1, MEG3, MEST, PEG3 and SNRPN) in 66 semen samples using the MSRE-qPCR method. The semen samples were divided into two groups according to the threshold value (25%) of DNA fragmentation index (DFI). We found that the mean methylation level at IGF2 (cg17037101) in the group with DFI ≥ 25% was lower than that in the group with DFI < 25% (13.7 ± 3% vs. 31.5 ± 5.3%, p = 0.0053). However, the methylation levels of other CpGs did not differ from the imprinted genes. Correlation analysis of DFI with the methylation levels of imprinted genes demonstrated that the IGF2 (cg17037101) methylation level was negatively correlated with sperm DFI (r = -0.448, p = 0.0038), and the KCNQ1 (cg24932449) methylation level was positively correlated with sperm DFI (r = 0.354, p = 0.0273). Our results suggest that the aberrant methylation of IGF2 and KCNQ1 genes may be associated with sperm DNA damage.
在精子中发现异常的印迹基因甲基化与不育有关。然而，精子 DNA 损伤与特定印迹基因甲基化之间的关系尚不清楚。在这项研究中，我们使用 MSRE-qPCR 方法在 66 个精液样本中确定了七个印迹基因座（H19、INS-IGF2、KCNQ1、MEG3、MEST、PEG3 和 SNRPN）的 DNA 甲基化水平。根据 DNA 碎片化指数（DFI）的阈值（25%）将精液样本分为两组。我们发现，DFI≥25%组 IGF2（cg17037101）的平均甲基化水平低于 DFI<25%组（13.7±3%比 31.5±5.3%，p=0.0053）。然而，其他 CpG 位点的甲基化水平与印迹基因没有差异。DFI 与印迹基因甲基化水平的相关分析表明，IGF2（cg17037101）甲基化水平与精子 DFI 呈负相关（r=-0.448，p=0.0038），而 KCNQ1（cg24932449）甲基化水平与精子 DFI 呈正相关（r=0.354，p=0.0273）。我们的结果表明，IGF2 和 KCNQ1 基因的异常甲基化可能与精子 DNA 损伤有关。
