溶血磷脂酸受体3和肝素结合样生长因子对胚胎反复移植失败的影响

Effects of lysophosphatidic acid receptor 3 and heparin-binding epidermal growth factor on repeated implantation failure

目的:通过研究人着床窗期子宫内膜组织中溶血磷脂酸受体3(LPAR3)和肝素结合表皮生长因子(HB-EGF)及其mRNA的表达,进一步探索反复移植失败的原因。方法:选取胚胎反复移植失败(RIF)患者23例为实验组,同期初次接受体外受精-胚胎移植(IVF-ET)助孕即妊娠的患者31例为对照组,着床窗期(排卵后第6～7天)微创法吸取少量子宫内膜组织,采用免疫组织化学SP法和半定量反转录-聚合酶链反应(RT-PCR),检测子宫内膜组织中LPAR3和HB-EGF及其mRNA的表达,并收集相关临床资料。结果:LPAR3和HB-EGF及其mRNA在两组患者的子宫内膜中均呈阳性表达,两者在部位和特点上存在一致性。RIF组的LPAR3和HB-EGF的平均光密度值明显低于对照组(P<0.01),LPAR3和HB-EGF mRNA表达亦明显低于对照组(P<0.01)。RIF组患者年龄、FSH使用天数(天)和剂量(IU)均明显高于对照组(P<0.05),而血P(μg/L)水平明显低于对照组(P<0.01)。结论:LPAR3参与了人子宫内膜容受性的建立过程,随着患者年龄的增长而表达降低,与HB-EGF在表达部位和特点上存在一致性,可作为预测子宫内膜容受性的良好参考指标。着床窗期血P水平降低、子宫内膜组织中LPAR3和HB-EGF的低表达可能导致胚胎反复移植失败的发生。

Objective： To further explore the causes of repeated implantation failure by researching the expressions of lysophospha- tidic acid receptor 3 （LPAR3）, heparin -binding epidermal growth factor （HB -EGF） and their mRNA in human endometrium during im- plantation window. Methods： Twenty -three patients with repeated implantation failure were selected as experimental group, while thirty - one patients who got pregnancy after in vitro fertilization and embryo transfer （ IVF - ET） for the first time during the same period were se- lected as control group, the specimens of endometrium during implantation window were obtained by minimally invasive surgery. Immunohis- tochemical SP assay and semi - quantitative RT - PCR were used to detect the expressions of LPAR3, HB - EGF and their mRNA, related clinical data were collected. Results： LPAR3, HB - EGF and their mRNA expressed positively in the specimens of endometrium in the two groups, there was consistency in the expression sites and characteristics. The mean values of optical density of LPAR3 and HB - EGF in ex- perimental group were significantly lower than those in control group （ P 〈 0. 01 ） , the expression levels of LPAR3 mRNA and HB - EGF mR- NA in experimental group were also significantly lower than those in control group （P 〈0. 01 ） . The age of patients, the usage time （unit： day） and dose of follicle stimulating hormone （FSH） in experimental group were significantly higher than those in control group （P 〈 0. 05 ） . The blood level of progesterone （unit： μg/L） in experimental group was significantly lower than that in control group （P 〈 0. 01 ） . Conclusion： LPAR3 is involved in the course of establishment of human endometrial receptivity, the expression of LPAR3 decreases with age, there is consistency in the expression sites and characteristics between LPAR3 and HB - EGF, and LPAR3 can be used as a good refer- enc＇e index to predict endometrial receptivity. The decrease of blood level of progesterone during implantation window, the low expression lev- els of LPAR3 and HB - EGF in endometrium may induce the occurrence of repeated implantation failure.