GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity
GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity
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DOI：
10.3892/mmr.2014.2680
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Qu, Xinlan
中科院分区：
文献类型：
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作者：
Li, Fei;Zhang, Ming;Qu, Xinlan
本研究旨在探讨促性腺激素释放激素类似物（GnRH-as），包括促性腺激素释放激素激动剂和拮抗剂，是否影响小鼠着床窗口期子宫内膜同源框（Hox）a10 DNA甲基化。使用GnRH类似物小鼠模型，并使用人绝经期促性腺激素（HMG）和GnRH激动剂或HMG和GnRH拮抗剂进行治疗。在GnRH类似物治疗或排卵后48小时收集子宫样本。亚硫酸氢盐测序聚合酶链反应（PCR），定量PCR和蛋白质印迹分析，以评估Hoxa 10和整合素3的表达。进行扫描电子显微镜分析以分析胞饮突的发育。与自然周期对照小鼠相比，GnRH类似物组小鼠表现出Hoxa 10启动子甲基化水平升高，Hoxa 10 mRNA和蛋白表达降低，胞饮突发育中断。这些结果表明，GnRH-as可能与Hoxa 10 DNA甲基化改变有关，因此GnRH-as可能影响子宫Hoxa 10表达和子宫内膜容受性。
The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin 3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.