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

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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。

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	刘慧敏
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	陈慧君
	张元珍

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

Abstract：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 receptor α(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 ERα and cofactor MLL1 in the promoter region of HOXA10.

Key words： Bisphenol A MLL1 HOXA10 Endometrial decidualization ERα

收稿日期: 2021-03-30

ZTFLH:

R71

基金资助:国家自然科学基金面上项目(81771543)

通讯作者: 张元珍(zhangyuanzhen@whu.edu.cn)

引用本文:

刘慧敏, 熊峣, 文雪, 耿婷, 张铭, 陈慧君, 张元珍. 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[J]. 中国生育健康杂志, 2023, 34(1): 60-65. LIU Huimin, XIONG Yao, WEN Xue, GENG Ting, ZHANG ming, CHEN Huijun, ZHANG Yuanzhen. The molecular mechanism of bisphenol A regulating the expression of endometrial decidualization molecular marker HOXA10 through MLL1. Chinese Journal of Reproductive Health, 2023, 34(1): 60-65.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2023/V34/I1/60

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