The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders.
The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders.
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DOI：
10.1097/gco.0000000000000071
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发表时间：
2014-06
影响因子：
2.1
通讯作者：
Seli E
中科院分区：
文献类型：
--
作者：
Uyar A;Seli E
基因组印记是指基因的等位基因特异性表达。基于DNA甲基化的分子机制调节早期胚胎发育和配子发生期间父母印记的建立和维持。由于时间上的一致性，在各种研究中已经调查了辅助生殖技术（ART）程序和印迹缺陷之间的潜在关联。在这篇综述中，我们提供了基因组印迹的概述，并提出了相关的临床数据的摘要。ART程序影响小鼠胚胎中DNA甲基化模式、亲本印迹状态和印迹基因表达。在人类中，几个病例系列表明ART和印记疾病之间存在关联，与普通人群相比，出生时患有Beckwith-Wiedemann综合征的儿童中ART使用的患病率高出三倍至六倍。然而，最近的研究未能支持这些发现，不能证明印记疾病和ART之间的关联，独立于生育力低下。ART程序可能会影响DNA中印记区域的甲基化状态，导致印记疾病。尽管印迹障碍的低患病率使得进行结论性临床试验具有挑战性，但需要在大型登记中心进行进一步研究，以确定ART对其发生的真实的影响。
Genomic imprinting refers to preferential allele-specific gene expression. DNA methylation-based molecular mechanisms regulate establishment and maintenance of parental imprints during early embryo development and gametogenesis. Because of the coincident timing, a potential association between assisted reproductive technology (ART) procedures and imprinting defects has been investigated in various studies. In this review, we provide an overview of genomic imprinting and present a summary of the relevant clinical data. ART procedures affect DNA methylation pattern, parental imprinting status, and imprinted gene expression in the mouse embryo. In humans, several case series suggested an association between ART and imprinting disorders, with a three-fold to six-fold higher prevalence of ART use among children born with Beckwith–Wiedemann syndrome compared to the general population. However, more recent studies failed to support these findings and could not demonstrate an association between imprinting disorders and ARTs, independent of subfertility. ART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.