An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells
An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells
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DOI：
10.1016/j.fertnstert.2007.03.078
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发表时间：
2008-05-01
影响因子：
6.7
通讯作者：
Terakawa, Naoki
中科院分区：
文献类型：
--
作者：
Izawa, Masao;Harada, Tasuku;Terakawa, Naoki
目的：探讨芳香化酶在子宫内膜异位症巧克力囊肿基质细胞培养中表达的分子基础。设计：前瞻性研究。地点：日本鸟取大学妇产科和生物信号学教研室。患者(S)：随机选择30例患者，分别接受腹腔镜手术(n=18)和开腹手术(n=12)。干预(S)：取子宫及卵巢巧克力囊肿内膜和异位内膜基质细胞。主要观察指标(S)：用酶免疫法测定培养液中雌二醇浓度。用实时定量聚合酶链式反应检测芳香酶的表达。使用独特的外显子I(PII、I.1、I.3、I.4、I.5和I.6)和外显子II引物检测启动子的使用。为确定5-氮杂脱氧胞苷对子宫内膜间质细胞的作用，将其作用96h。结果：子宫内膜异位症细胞分泌少量雌二醇到培养液中，而在培养液中加入睾酮则产生明显的雌二醇水平。在子宫内膜细胞中，即使在加入睾酮后，雌二醇的产生效率也远远低于子宫内膜异位症细胞。实时聚合酶链式反应分析表明，子宫内膜异位症细胞中芳香化酶信使RNA(MRNA)的表达上调。三个近端启动子，PII，1.3和1.6，驱动了mRNA的表达。在有少量芳香酶mRNA表达的子宫内膜细胞中，使用与子宫内膜异位症细胞相同的启动子。为探讨表观遗传修饰对子宫内膜异位症细胞芳香酶基因表达的影响，用5-氮杂脱氧胞苷处理子宫内膜细胞，可明显增强芳香酶基因的表达，并依赖于与子宫内膜异位症细胞相同的近端启动子。结论：表观遗传紊乱可能在子宫内膜异位症的病理生理过程中起一定作用。
Objective: To examine the molecular basis of aromatase expression in stromal cell culture from endometriotic chocolate cysts.Design: Prospective study.Setting: Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago Japan.Patient(s): Thirty women, selected randomly, who underwent laparoscopy (n = 18) or laparotomy (n = 12).Intervention(s): Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary.Main Outcome Measure(s): Estradiol concentrations in the culture media were measured by means of enzyme immunoassay. Aromatase expression was examined by quantitative real-time polymerase chain reaction. Promoter usage was examined using unique exon I (PII, I.1, I.3, I.4, I.5, and I.6) and exon II primers. To determine the effect of 5-aza-deoxycytidine on endometrial stromal cells, the cells were,treated with the agent for 96 hours.Result(s): Endometriotic cells secreted a marginal level of estradiol into the culture media, but adding testosterone to the culture produced a pronounced level of estradiol. In endometrial cells, estradiol production was far less efficient than in endometriotic cells even after adding testosterone Real-time polymerase chain reaction analyses demonstrated the up-regulation of aromatase messenger RNA (mRNA) expression in endometriotic cells. Three proximal promoters, PII, 1.3, and 1.6, drove mRNA expression. In endometrial cells where a marginal level of aromatase mRNA expression was observed, the same promoters as those in the endometriotic cells were used. To determine the role of epigenetic modification of aromatase gene expression in endometriotic cells, endometrial cells were treated with 5-aza-deoxycytidine, which markedly enhanced aromatase mRNA expression, depending on the same proximal promoters as those in endometriotic cells.Conclusion(s): An epigenetic disorder may play a role in the pathophysiology of endometriosis.