Aberrant sperm DNA methylation predicts male fertility status and embryo quality
Aberrant sperm DNA methylation predicts male fertility status and embryo quality
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DOI：
10.1016/j.fertnstert.2015.08.019
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发表时间：
2015-12-01
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.;Uren, Philip J.;Carrell, Douglas T.
目的：探讨基于全基因组精子脱氧核糖核酸甲基化模式预测体外受精(IVF)过程中男性生育状况和/或胚胎质量的可行性。设计：回顾性队列研究。地点：大学生育中心。患者(S)：参加体外受精治疗的男性127例(排除了女性主要不育因素)和54例正常生精、有生育能力的男性。体外受精患者被分成两组：胚胎发育总体良好且妊娠阳性的患者(n=55)，以及体外受精后胚胎发育普遍较差的患者(n=72；42例阳性妊娠和30例阴性妊娠)。干预(S)：采用全基因组精子DNA甲基化分析来检测基因组中485,000个位点的甲基化。主要结果(S)：比较了体外受精患者和正常受精者、有生育能力的男性的DNA甲基化模式。结果(S)：预测模型被证明对男性生育状态(生育或不育)具有很高的准确性，灵敏度为82%，阳性预测值为99%。层级聚类确定了为试管受精患者样本和质量较差的胚胎样本而丰富的集群。从整齐的样本中识别这些组内的样本所建立的模型，在每个病例中识别所有试管受精患者和劣质胚胎样本的五分之一时，获得了阳性预测值=94%。使用密度梯度制备的样本，相同的方法回收了46%的劣质胚胎样本，没有假阳性。结论(S)：不育和正常精子症男性精子DNA甲基化模式存在显著且一致的差异。此外，DNA甲基化模式可能预测体外受精过程中的胚胎质量。(C)2015年，由美国生殖医学学会提供。
Objective: To evaluate whether male fertility status and/or embryo quality during in vitro fertilization (IVF) therapy can be predicted based on genomewide sperm deoxyribonucleic acid (DNA) methylation patterns.Design: Retrospective cohort study.Setting: University-based fertility center.Patient(s): Participants were 127 men undergoing IVF treatment (where any major female factor cause of infertility had been ruled out), and 54 normozoospermic, fertile men. The IVF patients were stratified into 2 groups: patients who had generally good embryogenesis and a positive pregnancy (n = 55), and patients with generally poor embryogenesis (n = 72; 42 positive and 30 negative pregnancies) after IVF.Intervention(s): Genomewide sperm DNA methylation analysis was performed to measure methylation at > 485,000 sites across the genome.Main Outcome Measure(s): A comparison was made of DNA methylation patterns of IVF patients vs. normozoospermic, fertile men.Result(s): Predictive models proved to be highly accurate in classifying male fertility status (fertile or infertile), with 82% sensitivity, and 99% positive predictive value. Hierarchic clustering identified clusters enriched for IVF patient samples and for poor-quality-embryo samples. Models built to identify samples within these groups, from neat samples, achieved positive predictive value >= 94% while identifying > one fifth of all IVF patient and poor-quality-embryo samples in each case. Using density gradient prepared samples, the same approach recovered 46% of poor-quality-embryo samples with no false positives.Conclusion(s): Sperm DNA methylation patterns differ significantly and consistently for infertile vs. fertile, normozoospermic men. In addition, DNA methylation patterns may be predictive of embryo quality during IVF. (C) 2015 by American Society for Reproductive Medicine.