Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients
Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients
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DOI：
10.1093/hmg/ddm187
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发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Arima, Takahiro
中科院分区：
文献类型：
--
作者：
Kobayashi, Hisato;Sato, Akiko;Arima, Takahiro
最近的研究表明，辅助生殖技术（ART）涉及配子和早期胚胎的分离、处理和培养，与罕见印记疾病的发病率增加有关。主要的表观遗传事件发生在这段时间内，ART 的过程可能会使表观基因组受到外部影响，从而妨碍基因组印记的正确建立和维持。然而，不能简单地评估 ART 的风险，因为接受 ART 的患者在人口统计学和遗传上可能与育龄期的一般人群不同。在这项研究中，我们对从 97 名不育男性获得的精子 DNA 使用亚硫酸氢盐-PCR 限制性分析和测序组合技术检查了 7 个印记基因的 DNA 甲基化状态。我们在 14 名患者（14.4%）中发现了异常的父本甲基化印记，在 20 名患者（20.6%）中发现了异常的母本印记。这些双缺陷样本中的大多数是患有中度或重度少精症的男性。这些异常是印记位点特有的，因为我们发现这些样本中的整体 DNA 甲基化是正常的。对于具有异常 DNA 甲基化模式的精子，ART 的结果通常很差。然而，在 ICSI 中使用的一份同时具有父亲和母亲甲基化错误的精子样本产生了一个外观正常的孩子，其印记甲基化模式没有任何异常。我们的数据表明，来自不育患者的精子，尤其是少精子症患者的精子，可能会将不正确的初级印记传递给后代的风险更高，这凸显了对 ART 进行更多研究的必要性。
Recent studies suggest that assisted reproductive technologies (ART), which involve the isolation, handling and culture of gametes and early embryos, are associated with an increased incidence of rare imprinting disorders. Major epigenetic events take place during this time and the process of ART may expose the epigenome to external influences, preventing the proper establishment and maintenance of genomic imprints. However, the risks of ART cannot be simply evaluated because the patients who receive ART may differ both demographically and genetically from the general population at reproductive age. In this study, we examined the DNA methylation status of seven imprinted genes using a combined bisulphite-PCR restriction analysis and sequencing technique on sperm DNA obtained from 97 infertile men. We found an abnormal paternal methylation imprint in 14 patients (14.4%) and abnormal maternal imprint in 20 patients (20.6%). The majority of these doubly defective samples were in men with moderate or severe oligospermia. These abnormalities were specific to imprinted loci as we found that global DNA methylation was normal in these samples. The outcome of ART with sperm shown to have an abnormal DNA methylation pattern was generally poor. However, one sample of sperm with both paternal and maternal methylation errors used in ICSI produced a child of normal appearance without any abnormalities in their imprinted methylation pattern. Our data suggest that sperm from infertile patients, especially those with oligospermia, may carry a higher risk of transmitting incorrect primary imprints to their offspring, highlighting the need for more research into ART.