摘要
目的:检测子宫内膜异位症(EMs)在位及异位内膜HOXA10基因的表达及DNA的甲基化,探讨HOXA10基因异常表达及DNA异常甲基化在EMs发病及不孕机制中的状态和作用。方法:选择2009年1月至2010年8月在我院行腹腔镜手术治疗的卵巢子宫内膜异位囊肿患者20例(10例合并不孕)、非EMs患者20例(卵巢良性囊肿10例,输卵管因素不孕10例)。分别采取其在位、异位内膜及正常子宫内膜组织,采用荧光定量PCR方法检测HOXA10基因mRNA的表达,甲基化特异性聚合酶链反应(MSP)检测HOXA10基因3个启动子区F1、F2、F3的甲基化状态。结果:EMs在位和异位内膜组的HOXA10基因mRNA表达水平明显低于正常内膜(P<0.01),EMs在位内膜组总甲基化率45%(9/20),合并不孕患者甲基化率50%(5/10)。EMs异位内膜组总甲基化率40%(8/20),合并不孕患者甲基化率40%(4/10)。正常内膜组仅有1例卵巢成熟性畸胎瘤患者发生了甲基化,甲基化率5%(1/20)。EMs在位、异位内膜组总甲基化率及合并不孕患者甲基化率的差异无统计学意义(P=0.58,P=0.32),但与正常内膜组的差异均有显著统计学意义(P<0.01)。结论:HOXA10基因在EMs在位及异位内膜组织中均呈低表达状态,EMs中存在HOXA10基因DNA异常甲基化,EMs合并不孕患者内膜组织中HOXA10基因的DNA甲基化明显高于非EMs不孕患者。EMs中HOXA10基因的DNA异常甲基化可能与其发病及不孕机制有关,深入研究EMs中HOXA10基因DNA异常甲基化,有望为阻断EMs发病或治疗其引起的不孕提供新的思路。
Objective:To study the mRNA expression of HOXA10 gene and methylation of its promoter F1,F2 and F3 in the eutopic and ectopic endometrium of endometriosis disease as well as their relation with the development and progression and infertility of endometriosis.Methods:Twenty patients who received laparoscopic operation in our hospital between January of 2009 to August of 2010 because of ovary endometriosis(10 complicated with infertility)were selected as experimental group.Ten patients who received laparoscopic operation because of benign ovarian tumor and additional 10 patients of tubal infertility were collected as control group.Samples were extracted from 20 endometriosis eutopic and ectopic tissue(including 10 patients with infertility)and 20 normal endometrial tissue.The expression levels of HOXA10 mRNA were detected by real-time polymerase chain reaction.Methylation of HOXA10 gene promoters was verified by methylation specific PCR(MSP).Results:The level of mRNA expression of HOXA10 gene in the eutopic and ectopic endometrium of endometriosis was significantly lower than that in normal endometrium(P0.01).In the eutopic group,the total methylation rate of promoters was 45%(9/20),and in infertility subgroup,the methylation rate was 50%(5/10).In the ectopic endometrium,the total methylation of promoters was 40%(8/20),and in infertility,methylation was 40%(4/10).Methylation in normal endometrium was 5%(1/20)and methylation in tubal infertility subgroup was 0%(0/10).There was significant difference between endometrosis(both eutopic and ectopic endometrium)and normal endometrium tissue(P0.01).While there was no significant difference between eutopic and ectopic endometrium(P0.05).Conclusions:Methylation of HOXA10 gene promoters is one of the important mechanisms of endometriosis and its related infertility.Further investigation might offer a new method to the treatment of endometriosis and its related infertility.
出处
《现代妇产科进展》
CSCD
北大核心
2011年第11期868-872,共5页
Progress in Obstetrics and Gynecology
基金
广东省卫生厅项目(No:B2009239)