Uyar Asli, Seli Emre
aDepartment of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA bDepartment of Computer Engineering, Okan University, Tuzla, Istanbul, Turkey.
Curr Opin Obstet Gynecol. 2014 Jun;26(3):210-21. doi: 10.1097/GCO.0000000000000071.
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.
基因组印记是指等位基因特异性的基因表达偏好。基于DNA甲基化的分子机制在早期胚胎发育和配子发生过程中调控亲本印记的建立和维持。由于时间上的巧合，在各项研究中已对辅助生殖技术（ART）程序与印记缺陷之间的潜在关联进行了调查。在本综述中，我们概述了基因组印记，并总结了相关临床数据。
ART程序会影响小鼠胚胎中的DNA甲基化模式、亲本印记状态和印记基因表达。在人类中，几个病例系列提示ART与印记障碍之间存在关联，与一般人群相比，患有贝克威思-维德曼综合征的儿童中使用ART的患病率高出三到六倍。然而，最近的研究未能支持这些发现，且无法证明印记障碍与ART之间存在关联，与不育无关。
ART程序可能会影响DNA中印记区域的甲基化状态，导致印记障碍。尽管印记障碍的患病率较低，使得进行确定性临床试验具有挑战性，但仍需要在大型登记处进行进一步研究，以确定ART对其发生的实际影响。
