Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception.
Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception.
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DOI：
10.1093/molehr/gap107
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发表时间：
2010-09
影响因子：
4
通讯作者：
U. Zechner;G. Pliushch;E. Schneider;N. El Hajj;A. Tresch;Y. Shufaro;L. Seidmann;W. Coerdt;Annette M. Müller;T. Haaf
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文献类型：
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作者：
U. Zechner;G. Pliushch;E. Schneider;N. El Hajj;A. Tresch;Y. Shufaro;L. Seidmann;W. Coerdt;Annette M. Müller;T. Haaf
为了研究辅助生殖技术（ART）对表观遗传重编程的可能影响，我们分析了7个印迹基因的差异甲基化区域（DMR）的DNA甲基化水平（H19，MEG3，LIT 1，MEST，NESP 55，PEG 3和SNRPN）以及绒毛样品（CVS）中多能性基因NANOG和肿瘤抑制基因APC的启动子区42例ART后自然流产和死产，29例自然受孕后流产/死产。我们没有发现ART后错误甲基化模式的比率增加，但ART和非ART样本之间LIT 1（P = 0.006）和H19（P = 0.085）的甲基化水平存在显著差异和趋势差异（ROC曲线分析，Wilcoxon检验）。除了NANOG可能的例外，我们没有观察到胎龄对所研究基因甲基化水平的影响。PEG 3和APC中极端甲基化值的频率明显高于其他研究基因，表明某些基因对表观遗传改变的易感性增加。CVS中的大多数甲基化异常要么代表父方和母方印记基因的高甲基化DMR，要么代表非印记基因的低甲基化启动子。所观察到的甲基化异常（镶嵌现象）与早期胚胎发生期间的甲基化重编程缺陷一致。
To study possible effects of assisted reproductive technologies (ART) on epigenetic reprogramming, we have analyzed the DNA methylation levels of differentially methylated regions (DMRs) of seven imprinted genes (H19, MEG3, LIT1, MEST, NESP55, PEG3 and SNRPN) as well as the promoter regions of the pluripotency gene NANOG and the tumor suppressor gene APC in chorionic villus samples (CVS) of 42 spontaneous miscarriages and stillbirths after ART and 29 abortions/stillbirths after spontaneous conception. We did not find an increased rate of faulty methylation patterns after ART, but significant and trend differences (ROC curve analysis, Wilcoxon test) in the methylation levels of LIT1 (P = 0.006) and H19 (P = 0.085) between ART and non-ART samples. With the possible exception of NANOG, we did not observe a gestational age effect on the methylation levels of the studied genes. The frequency of extreme methylation values in PEG3 and APC was markedly higher than in the other studied genes, indicating an increased susceptibility of some genes to epigenetic alterations. Most methylation abnormalities in CVS represented either hypermethylated DMRs of paternally and maternally imprinted genes or hypomethylated promoters of non-imprinted genes. The observed methylation abnormalities (mosaicism) are consistent with methylation reprogramming defects during early embryogenesis.