摘要
目的:探讨组蛋白甲基化酶MLL1在小鼠围着床期子宫内膜的表达规律及对胚胎着床的作用。方法:收集妊娠小鼠(D0、D1、D4、D5、D6、D8)子宫内膜,分别采用RT-PCR和Western Blot检测小鼠内膜MLL1 mRNA和蛋白的表达情况,利用免疫组化检测MLL1蛋白的定位;宫角注射MLL1抑制剂进行干预。结果:①MLL1、HOXA10 mRNA的表达量在妊娠后随天数逐渐上升,且在D4达到高峰(P<0. 05),而后逐渐下降;②免疫印迹发现MLL1蛋白,与mRNA表达趋势相同,在小鼠妊娠后上调,D4表达最强(P<0. 05),而后下降;免疫组化发现在D0和D1、D4,MLL1蛋白主要表达于子宫内膜腔上皮和腺上皮;妊娠D5,MLL1主要表达于子宫基质细胞中,妊娠D6、D8主要表达于蜕膜化细胞中;③宫角注射MLL1抑制剂后,与空白组相比,抑制组胚胎着床数量明显减少,并且MLL1 mRNA和蛋白的表达水平低于溶剂组和空白对照组。结论:组蛋白甲基化酶MLL1可能参与了子宫内膜容受性的建立和胚胎植入的过程;还可能参与了胚胎植入后的子宫内膜蜕膜化反应。
Objective: To investigate the expression and the role of MLL1 during peri-implantation process of embryos.Methods: The endometrium samples in early pregnant mice(D0, D1, D4, D5, D6, D8)were collected, and the expression level of MLL1 mRNA and MLL1 protein were determined by RT-PCR and Western Blot, respectively, and the distribution of MLL1 was performed by immunohisto-chemistry, mices were given an intrauterine injection of the inhibitor of MLL1.Results: The expression of MLL1 and HOXA10 mRNA in endometrium of pregnant mice were gradually increased as days went, and it reached a peak at pregnant day 4(P<0. 05) and declined thereafter. The expression level of MLL1 protein has same trend as the MLL1 mRNA expression level,the MLL1 protein level presented an upregulated trend and reached a peak on D4(P<0. 05) of pregnancy and decreased there-after. Immunohistochemistry displays that the MLL1 protein was located mainly in luminal epithelium and glandular epithelium on D0, D1, and D4. On D5, MLL1 protein could be detected in stromal cells, and on the D6 and D8, the MLL1 protein was exhibited in decidualized cells. The number of im-planted embryos in the uterus horns after injecting inhibitor was markedly decreased as compared with that in control groups, and the expression levels of MLL1 mRNA and protein were lower than those of the blank group and solvent control.Conclusion: Histone methyltransferases MLL1 involves in the development of endometrial receptivity and the process of embryo implantation,besides, MLL1 may play an important role in decidualization of endometrium.
引文
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