Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis
Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis
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DOI：
10.1016/j.fertnstert.2011.11.008
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发表时间：
2012-02-01
影响因子：
6.7
通讯作者：
Carrell, Douglas T.
中科院分区：
文献类型：
--
作者：
Aston, Kenneth I.;Punj, Vasu;Carrell, Douglas T.
目的：为了评估精子染色质包装异常的男性和IVF后在没有已知女性因素的情况下显示异常胚胎发生的患者的精子全基因组DNA甲基化模式，设计：病例对照研究，设置：大学男科和研究实验室，患者：鱼精蛋白1/鱼精蛋白2比值异常高和低的男性（n = 15）;接受IVF/卵胞浆内单精子注射导致胚胎发生异常的患者（n = 13）;和精子正常、生育力正常的对照组（n = 15）。使用Illumina Infinium HumanMethylation 27 BeadChip测定法测量全基因组精子DNA甲基化。采用亚硫酸氢盐焦磷酸测序法进行后续的靶向甲基化分析。主要结果测量：在超过27，000个CpG全基因组的甲基化水平上进行组间比较。但是，在此情况下，两名男子与异常鱼精蛋白1/鱼精蛋白2和一名异常胚胎发生患者在大量CpG上显示出显著改变的甲基化模式。印迹区域比基因组更容易失调。结论：我们已经确定了三个人显示广泛的破坏精子DNA甲基化谱。虽然分析的样本集相对较小，但这些结果表明精子DNA甲基化的广泛破坏可能是某些不育男性的重要特征。功能研究将是必要的，以表征这种表观遗传破坏的发育后果。（Fertil Steril（R）2012;97：285-92.（c）2012年由美国生殖医学学会。
Objective: To evaluate genome-wide DNA methylation patterns in sperm from men with abnormal sperm chromatin packaging and patients displaying abnormal embryogenesis after IVF in the absence of known female factors.Design: Case-control study.Setting: University andrology and research laboratory.Patient(s): Men with abnormally high and low protamine 1/protamine 2 ratio (n = 15); patients who have undergone IVF/intracytoplasmic sperm injection resulting in abnormal embryogenesis (n = 13); and normozoospermic, fertile controls (n 15).Intervention(s): Genome-wide sperm DNA methylation was measured using the Illumina Infinium HumanMethylation27 BeadChip assay. Follow-up targeted methylation analysis was performed using bisulfite pyrosequencing.Main Outcome Measure(s): Methylation levels at more than 27,000 CpGs genome-wide were compared between groups.Result(s): Of the 43 men analyzed, 40 displayed highly concordant methylation patterns; however, two men with abnormal protamine 1/protamine 2 and one abnormal embryogenesis patient displayed significantly altered methylation patterns across a large number of CpGs. Imprinted regions were more prone to deregulation than the genome at large.Conclusion(s): We have identified three individuals displaying broad disruption of sperm DNA methylation profiles. Although the sample set analyzed is relatively small, these results indicate that broad disruptions in sperm DNA methylation may be an important signature in some infertile men. Functional studies will be necessary to characterize the developmental consequences of such epigenetic disruption. (Fertil Steril (R) 2012;97:285-92. (c)2012 by American Society for Reproductive Medicine.)