Universität des Saarlandes, FR 8.3 Biowissenschaften, Genetik/Epigenetik, Postfach 151150, D-66041 Saarbrücken, Germany.
J Med Genet. 2010 Jun;47(6):371-6. doi: 10.1136/jmg.2009.073189. Epub 2009 Nov 30.
BACKGROUND Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are believed to destabilise genomic imprints. An increased frequency of Beckwith-Wiedemann syndrome in children born after ART has been reported. Other, mostly epidemiological, studies argue against this finding. OBJECTIVE To examine the effect of ART on the stability of DNA methylation imprints, DNA was extracted from maternal peripheral blood (MPB), umbilical cord blood (UCB) and amnion/chorion tissue (ACT) of 185 phenotypically normal children (77 ICSI, 35 IVF, and 73 spontaneous conceptions). Using bisulfite based technologies 10 differentially methylated regions (DMRs) were analysed, including KvDMR1, H19, SNRPN, MEST, GRB10, DLK1/MEG3 IG-DMR, GNAS NESP55, GNAS NESPas, GNAS XL-alpha-s and GNAS Exon1A. RESULTS Methylation indices (MI) do not reveal any significant differences at nine DMRs among the conception groups in neither MPB, UCB nor in ACT. The only slightly variable DMR was that of MEST. Here the mean MI was higher in UCB and MPB of IVF cases (mean MI+/-SD: 0.41+/-0.03 (UCB) and 0.40+/-0.03 (MPB)) compared to the ICSI (0.38+/-0.03, p=0.003 (UCB); 0.37+/-0.04, p=0.0007 (MPB)) or spontaneous cases (0.38+/-0.03, p=0.003 (UCB); 0.38+/-0.04, p=0.02 (MPB)). Weak but suggestive correlations between DMRs were, however, found between MPB, UCB and ACT. CONCLUSION This study supports the notion that children conceived by ART do not show a higher degree of imprint variability and hence do not have an a priori higher risk for imprinting disorders.
辅助生殖技术（ART），如体外受精（IVF）和胞浆内精子注射（ICSI），被认为会破坏基因组印记。有报道称，ART 后出生的儿童中 Beckwith-Wiedemann 综合征的发病率增加。其他大多数流行病学研究则反对这一发现。目的：检查 ART 对 DNA 甲基化印记稳定性的影响，从 185 名表型正常的儿童的母亲外周血（MPB）、脐带血（UCB）和羊膜/绒毛膜组织（ACT）中提取 DNA。使用基于亚硫酸氢盐的技术分析了 10 个差异甲基化区域（DMR），包括 KvDMR1、H19、SNRPN、MEST、GRB10、DLK1/MEG3 IG-DMR、GNAS NESP55、GNAS NESPas、GNAS XL-alpha-s 和 GNAS Exon1A。结果：在 MPB、UCB 和 ACT 中，9 个 DMR 的甲基化指数（MI）在受孕组之间没有显示出任何显著差异。唯一稍微可变的 DMR 是 MEST。在这里，IVF 病例的 UCB 和 MPB 中的平均 MI 较高（UCB 的平均 MI+/-SD：0.41+/-0.03；MPB 的平均 MI+/-SD：0.40+/-0.03），而 ICSI（0.38+/-0.03，p=0.003（UCB）；0.37+/-0.04，p=0.0007（MPB））或自然受孕病例（0.38+/-0.03，p=0.003（UCB）；0.38+/-0.04，p=0.02（MPB））。然而，DMR 之间存在微弱但提示性的相关性，MPB、UCB 和 ACT 之间存在相关性。结论：这项研究支持这样一种观点，即通过 ART 受孕的儿童不会显示出更高程度的印记变异性，因此，他们没有先天的更高的印记障碍风险。
