南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (10): 1498-.

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基因组DNA甲基化水平与不明原因早期自然流产的相关性

晁远，翁立冬，曾嵘   

  • 出版日期:2014-10-20 发布日期:2014-10-20

Correlation of genomic DNA methylation level with unexplained early spontaneous
abortion

  • Online:2014-10-20 Published:2014-10-20

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摘要： 目的探讨基因组DNA甲基化水平与人不明原因早期自然流产的关系并从mRNA表达量上研究DNMT1、DNMT3A和
DNMT3B在自然流产绒毛DNA甲基化中的作用。方法收集45例核型正常自然流产绒毛组织及其中33例母亲外周血和44例
核型正常人工流产绒毛组织及其中34例母亲外周血，采用高效液相色谱法（HPLC）测定基因组DNA甲基化水平并用荧光定量
PCR法检测其中33例人工流产绒毛和30例自然流产绒毛DNMT mRNA的表达。结果（1）自然流产绒毛组DNA甲基化水平
低于人工流产绒毛组（P<0.01）；（2）自然流产母亲组和人工流产母亲组间DNA甲基化水平差异无统计学意义（P>0.05）；（3）自
然流产绒毛组DNMT1和DNMT3A mRNA的表达低于人工流产绒毛组（P<0.05）；（4）自然流产绒毛组DNMT3B mRNA的表达
与人工流产绒毛组差异无统计学意义（P>0.05）。结论（1）人类早期自然流产中确实存在着绒毛组织基因组DNA甲基化的不
足；（2）自然流产绒毛中DNA甲基化的不足可能与DNMT1和DNMT3A表达降低有关。

Abstract: Objective To investigate the correlation of genomic DNA methylation level with unexplained early spontaneous
abortion and analyze the role of DNMT1, DNMT3A and DNMT3B. Methods Forty-five villus samples from spontaneous
abortion cases (with 33 maternal peripheral blood samples) and 44 villus samples from induced abortion (with 34 maternal
peripheral blood samples) were examined with high-pressure liquid chromatography (HPLC) to measure the overall
methylation level of the genomic DNA. The expressions of DNMT mRNAs were detected using fluorescence quantitative-PCR
in the villus samples from 33 induced abortion cases and 30 spontaneous abortion cases. Results Genomic DNA methylation
level was significantly lower in the villus in spontaneous abortion group than in induced abortion group (P<0.01), but similar
in the maternal blood samples between the two groups (P>0.05). The mean mRNA expression levels of DNMT1 and DNMT3A
in the villus were significantly lower in spontaneous abortion group than in induced abortion group (P<0.05), but DNMT3B
expression showed no significant difference between them (P>0.05). Conclusion Insufficient genomic DNA methylation in the
villus does exist in human early spontaneous abortion, and this insufficiency is probably associated with down-regulated
expressions of DNMT1 and DNMT3A.