摘要
目的:探讨根治性宫颈切除术(radical trachelectomy,RT)患者术后同源盒基因A11(HOXA11)的表达对子宫内膜容受性的影响。方法:应用实时聚合酶链反应(real-time PCR)检测RT术后不孕症患者(n=16)与正常生育能力女性(n=16)分泌期子宫内膜组织中HOXA11基因的m RNA表达水平,并应用蛋白质印迹法(Western blotting)分别检测2组患者分泌期子宫内膜组织中HOXA11、整合素β3(Integrin-β3)以及β-catenin、Dickkopf-1(DKK1)蛋白的表达水平。结果:HOXA11基因在RT组和对照组的分泌期子宫内膜中均有表达,但RT组低于对照组,差异有统计学意义(P<0.05);HOXA11、Integrin-β3以及β-catenin、DKK1蛋白在RT组的表达也低于对照组,差异有统计学意义(P<0.05)。且HOXA11与Intergin-β3蛋白、β-catenin蛋白及DKK1蛋白的表达强度均呈显著正相关(P分别为0.006、0.004和0.007)。结论:在RT术后不孕可能由于宫颈组织的缺失从而影响宫腔内HOXA11基因的正常表达,并相应调节Integrin-β3及Wnt/β-catenin通路的表达,从而干扰子宫内膜容受性的形成,导致胚胎着床失败而不孕。
Objective:To measure the expression levels of HOXA11 m RNA and protein in endometrial tissues of patients after radical trachelectomy(RT), and to investigate the effect of HOXA11 on endometrial receptivity.Methods: There were two groups in this study. The RT group included 16 infertile patients after RT treatment.Another group included 16 fertile patients after RT as control. The endometrial tissue was biopsied with the informed consent. The expression of HOXA11 m RNA in endometrial tissue was detected by real-time RT-PCR.The expression levels of HOXA11, Integrin-β3, β-catenin and DKK1 proteins were measured by Western blots.Results: The expression of HOXA11 m RNA in the RT infertile group was significantly lower than that in the control group(P<0.05). The expression levels of HOXA11, Integrin-β3, β-catenin and DKK1 proteins in the RT infertile group were significantly lower than those in the control group(all P<0.05). Interestingly, the expression level of HOXA11 was positively correlated with the expression level of Intergin-β3, β-catenin or DKK1,respectively(P values were 0.006, 0.004 and 0.007). Conclusions: The expression of HOXA11 in endometrial tissue was significantly decreased in those infertile patients after RT, which down regulated the expression of integrin-β3 and the Wnt/β-catenin pathway related with endometrial receptivity. This is one of the possible mechanisms of the failed embryo implantation and infertile outcome.
引文
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