General imprinting status is stable in assisted reproduction-conceived offspring
General imprinting status is stable in assisted reproduction-conceived offspring
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辅助生殖受孕后代的一般印记状态是稳定的
DOI：
10.1016/j.fertnstert.2011.09.033
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发表时间：
2011-12-01
影响因子：
6.7
通讯作者：
Huang, He-Feng
中科院分区：
文献类型：
--
作者：
Feng, Chun;Tian, Shen;Huang, He-Feng
目的：目的：探讨辅助生殖技术（ART）妊娠后代的基因印迹状态是否稳定。设计：前瞻性临床观察研究。地点：大学附属教学医院体外受精（IVF）中心。患者：60例ART妊娠婴儿（30例IVF和30例卵胞浆内单精子注射[ICSI]）和60例自然受孕婴儿。采集脐带血和外周血样本。主要结果测量：采用基因芯片和实时荧光定量逆转录聚合酶链反应（real-time reverse transcriptionpolymerase chain reaction，PCR）检测基因表达谱，PCR后直接测序检测等位基因特异性表达，结果：系统聚类分析显示ART组与自然受孕组的子代之间无明显聚类，提示ART组与自然受孕组的子代基因组印记表达相似。在ART受孕的后代中鉴定出三个差异表达基因，其中PEG 10和L3 MBTL上调，PHLDA 2下调。差异表达的印迹基因的等位基因特异性表达在大多数ART和自然受孕的后代中得以维持。然而，在一例ICSI病例中，L3 MBTL的单等位基因表达被破坏，所有CpG均完全未甲基化。这些都不是遗传自父母。结论：印迹的全球概况是稳定的，通过ART受孕的孩子。然而，一些特定的印迹基因的印迹可能是脆弱的ART受孕的孩子的一小部分。（Fertil Steril（R）2011; 96：1417-23. (C)美国生殖医学会（American Society for Reproductive Medicine）
Objective: To evaluate whether the genomic imprinting status of assistant reproductive technology (ART)conceived offspring is stable.Design: Prospective clinical observational study.Setting: In vitro fertilization (IVF) center, university-affiliated teaching hospital.Patient(s): Sixty ART-conceived babies (30 IVF and 30 intracytoplasmic sperm injection [ICSI]) and 60 naturally conceived babies.Intervention(s): Collection of umbilical cord blood and peripheral blood samples.Main Outcome Measure(s): Expression profile was examined by microarray and real-time reverse-transcription polymerase chain reaction (PCR), allele-specific expression was studied by direct sequencing after PCR, and DNA methylation status was investigated by sodium bisulfite sequencing.Result(s): Hierarchic clustering demonstrated no obvious clustering between the ART-and naturally conceived offspring, suggesting similar genomic imprinting expression between the two groups. Three differentially expressed genes were identified in ART-conceived offspring, with PEG10 and L3MBTL up-regulated and PHLDA2 down-regulated. Allele-specific expression of the differentially expressed imprinted genes was maintained in the majority of the ART-and naturally conceived offspring. However, in one ICSI case, monoallelic expression of L3MBTL was disrupted and all CpGs were completely unmethylated. These were not inherited from the parents.Conclusion(s): The global profile of imprinting is stable in children conceived through ART. However, imprinting of a few specific imprinted genes may be vulnerable in a fraction of ART-conceived children. (Fertil Steril (R) 2011; 96: 1417-23. (C) 2011 by American Society for Reproductive Medicine.)