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妊娠早期丢失中 IGF2-AS 启动子的异常甲基化。

Aberrant methylation of IGF2-AS promoter in early pregnancy loss.

机构信息

Center for Reproductive Medicine, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, People's Republic of China; Institute of Gynecology and Obstetrics, Guangzhou Medical University Second Affiliated Hospital, Guangzhou 510260, People's Republic of China.

Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510020, People's Republic of China.

出版信息

Taiwan J Obstet Gynecol. 2020 Jan;59(1):109-114. doi: 10.1016/j.tjog.2019.11.017.

Abstract

OBJECTIVE

The present study aimed to evaluate insulin-like growth factor 2 antisense (IGF2-AS) in the villi of human embryos and compared its expression between normal pregnancy and early pregnancy loss (EPL).

MATERIALS AND METHODS

The present study conducted a microarray analysis to identify the expression profiles of lncRNAs in villi from EPL and normal controls (controls, n = 10 and EPL patients, n = 10). Embryonic villi were collected from women who underwent artificial abortion. QPCR was used to confirm the results. The DNA methylation patterns were analyzed using pyrosequencing and bisulfite sequencing polymerase chain reaction. The percentage of methylation was compared in chorionic villi from the two groups.

RESULTS

A total of 57 deregulated differentially expressed lncRNAs were detected, of which 33 were upregulated, and 24 were downregulated. The expression of lncRNA IGF2-AS was downregulated significantly in EPL villi compared with the normal villi. Negative regulation of IGF2-AS may be involved in the development of EPL. Methprimer predicted that IGF2-AS promoter had CpG islands and dense CG sites. Increased methylation at CpG islands present in IGF2-AS gene promoter was observed in EPL villi.

CONCLUSION

An increase in methylation of IGF2-AS likely leads to its downregulation in chorionic villi of EPL. The findings suggest that a deficiency of IGF2-AS in the villi is associated with human EPL.

摘要

目的

本研究旨在评估人胚胎绒毛中的胰岛素样生长因子 2 反义(IGF2-AS),并比较其在正常妊娠和早期妊娠丢失(EPL)中的表达。

材料和方法

本研究通过微阵列分析鉴定 EPL 和正常对照组(对照组,n=10;EPL 患者,n=10)绒毛中 lncRNA 的表达谱。胚胎绒毛取自行人工流产的妇女。采用 QPCR 验证结果。采用焦磷酸测序和亚硫酸氢盐测序聚合酶链反应分析 DNA 甲基化模式。比较两组绒毛中甲基化的百分比。

结果

共检测到 57 个差异表达的下调 lncRNA,其中 33 个上调,24 个下调。EPL 绒毛中 lncRNA IGF2-AS 的表达明显低于正常绒毛。IGF2-AS 的负调控可能参与了 EPL 的发生。Methprimer 预测 IGF2-AS 启动子有 CpG 岛和密集的 CG 位点。在 EPL 绒毛中观察到 IGF2-AS 基因启动子中 CpG 岛的甲基化增加。

结论

IGF2-AS 的甲基化增加可能导致其在 EPL 绒毛中的下调。研究结果表明,IGF2-AS 在绒毛中的缺乏与人类 EPL 有关。

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