双酚A通过MLL1调控子宫内膜蜕膜化分子标志物HOXA10表达的分子机制  

The molecular mechanism of bisphenol A regulating the expression of endometrial decidualization molecular marker HOXA10 through MLL1

作　　者：刘慧敏 熊峣 文雪[1] 耿婷 张铭[1] 陈慧君[1] 张元珍[1] LIU Huimin;XIONG Yao;WEN Xue;GENG Ting;ZHANG ming;CHEN Huijun;ZHANG Yuanzhen(Dept.of Reproductive Center,Zhongnan Hospital of Wuhan University&Hubei Clinical Research Center forPrenatal Diagnosis and Birth Health,430071)

机构地区：[1]武汉大学中南医院生殖医学中心/湖北省产前诊断与优生临床医学研究中心,430071

出　　处：《中国生育健康杂志》2023年第1期60-65,共6页Chinese Journal of Reproductive Health

基　　金：国家自然科学基金面上项目(81771543)。

摘　　要：目的探讨组蛋白甲基化转移酶混合谱系白血病基因(MLL1)在双酚A(Bisphenol,BPA)影响子宫内膜间质细胞蜕膜化中的作用机制。方法CCK-8实验检测10pM、10nM、10μM BPA对细胞增殖能力的影响;RT-PCR和Western Blot检测BPA暴露后蜕膜化子宫内膜间质细胞中的MLL1及同源盒基因A10(HOXA10)mRNA和蛋白表达情况;CoIP实验验证MLL1和雌激素受体α(ERα)是否相互结合,以及BPA是否影响两者的结合;ChIP检测MLL1和ERα在HOXA10启动子区的富集效率。结果三种浓度BPA均不损害细胞的增殖能力;蜕膜化子宫内膜间质细胞中MLL1和HOXA10 mRNA和蛋白表达随着BPA浓度的升高逐渐降低;MLL1是ERα的共同作用因子,BPA暴露影响MLL1与ERα的结合;BPA暴露抑制了MLL1和ERα在HOXA10启动子ERE元件区域的富集。结论BPA通过影响转录因子ERα和共同作用因子MLL1在HOXA10启动子区的富集,调控HOXA10的表达,影响子宫内膜间质细胞蜕膜化。Objective To explore the mechanism of histone methyltransferase mixed lineage leukaemia histone methylase 1(MLL1)in the effect of bisphenol A(BPA)on the decidualization of endometrial stromal cells.Methods CCK-8 experiment was used to detect the effects of 10pM,10nM,and 10μM BPA on cell proliferation;RT-PCR and Western Blot were used to detect the expression of MLL1 and Homeobox A10(HOXA10)mRNA and protein in decidualized endometrial stromal cells after BPA exposure;CoIP experiment verifies whether MLL1 and Estrogen receptorα(ERα)bind to each other,and whether BPA affects the combination of the two;ChIP detects the enrichment efficiency of MLL1 and ERa in the HOXA10 promoter region.Results The three concentrations of BPA do not damage the proliferation ability of cells;the expression of MLL1 and HOXA10 mRNA and protein in decidualized endometrial stromal cells gradually decrease with the increase of BPA concentration;MLL1 is a cofactor of ERα,BPA exposure affects the binding of MLL1 and ERa;BPA inhibits the enrichment of MLL1 and ERa in the ERE element region of the HOXA10 promoter.Conclusion Bisphenol A regulates the expression of HOXA10 and affects the decidualization of endometrial stromal cells by affecting the enrichment of transcription factor ERαand cofactor MLL1 in the promoter region of HOXA10.

关 键 词：双酚A 混合谱系白血病基因1 同源盒基因A10 子宫内膜蜕膜化 雌激素受体Α 

分 类 号：R71[医药卫生—妇产科学]