子宫内膜整合素αvβ3表达与体外受精-胚胎移植反复种植失败的相关性研究

摘要

目的 研究整合素αvβ3在人各时期子宫内膜及蜕膜组织的表达,并探讨其与体外受精-胚胎移植(IVF-ET)反复种植失败的相关性.方法 以40例IVF-ET治疗反复种植失败的患者为研究对象,以40例因男性因素行卵胞浆内单精子注射(ICSI)治疗的患者及5例正常孕早期患者作为对照,获取患者各个时期的子宫内膜及蜕膜组织,采用免疫组织化学法检测整合素αvβ3蛋白的定位和表达,并对所获得的结果应用Image-Pro Plus 6.0图像分析软件测定阳性反应强度.结果 整合素αvβ3蛋白定位于子宫内膜腺上皮细胞和腔上皮细胞的细胞浆;增殖早、中、晚期及分泌早期内膜上均无表达,分泌中期、晚期内膜明显表达,蜕膜中表达最强(P<0.05).反复种植失败患者子宫内膜整合素αvβ3的表达同样存在周期性变化,但其在分泌中、晚期的表达要明显弱于对照组,差异有统计学意义 (P<0.05).结论 整合素αvβ3在正常子宫内膜组织中的表达呈现明显周期依赖性,与胚胎种植密切相关;而其在IVF-ET反复种植失败患者种植窗期子宫内膜组织中的表达明显减弱,可能是导致胚胎种植失败的原因之一.%Objective: To investigate the expression of integrin αvβ3 in human endometrium throughout the menstrual cycle and in deciduas in early pregnancy, and explore its correlation with recurrent implantation failure in in vitro fertilization and embryo transfer (IVF-ET).Methods: Forty patients with recurrent implantation failure in IVF-ET treatment were analyzed as study group. Other 40 patients undergoing intracytoplasmic sperm injection (ICSI) due to male factors and 5 normal pregnant patients with induced abortion were as control group. The samples of endometrium throughout the menstrual cycle were obtained in patients before IVF-ET and ICSI treatment. The samples of deciduas were obtained from 5 normal pregnant patients with induced abortion. Immunohistochemistry was used to measure the expression of integrin αvβ3 protein in all samples.Results: Integrin αvβ3 mainly expressed in cytoplasm of endometrial glandular epithelial cells and luminal epithelial cells. There was no expression of integrin αvβ3 in proliferative phase or early secretory phase. And the expression was obviously increased in middle and late secretory phase and was the highest in deciduas (P＜0. 05). The expressions in middle and late secretory phase were higher than those in proliferative phase of patients with recurrent implantation failure, but it was weaker than that of control group (P＜0.05).Conclusions: Integrin αvβ3 protein showed a pronounced menstrual cycle-dependent expression in cycling endometrium, which is probably involved in embryo implantation. The expressions in middle and late secretory phase of patients with recurrent implantation failure were weaker than those of control group, and it may be one of the reasons that caused implantation failure.