雌激素膜受体介导的非基因组效应对反复种植失败患者子宫内膜的影响

It is recently found that insufficient proliferation of endometrium is the key reason for repeated embryo implantation failure (RIF), it has been confirmed that the estrogen responding genes was down regulated in the endometrium of RIF patients. However, as the first responder, the estrogen membrane receptor Gper has been neglected all the time, and its role is exactly regulating cell proliferation and differentiation through non-genomic effect. It has been proved in our previous study that Gper, a novel membrane receptor existed in the endometrium, mediating the high level of estrogen regulation in the endometrial receptivity. Further study showed that the expression of Gper was down regulated in the endometrium of RIF patients. Thus, We put forward here a new mechanism of RIF: Endometrial Gper down regulation made the endometrial cells response to estrogen suppressed, so that affect proliferation of endometrial cells, eventually leading to the occurrence of RIF. The project intends to aim at obtaining the direct evidence of deficiencies proliferation in RIF patients’ endometrium caused by Gper abnormal response to estrogen, to confirm that deficiencies proliferation is the reason of poor potential of embryo implantation in RIF patients. The project is expected to reveal the internal mechanisms of endometrial implantation potential in RIF regulated by Gper, and provide more adequate scientific basis for clinical treatment in RIF.

最近发现子内膜增殖不充分是反复种植失败(RIF)的主要原因,并证实RIF患者内膜上雌激素核受体及其介导的基因组效应元件显著下调。然而,最先应答雌激素的膜受体Gper一直被忽略,其作用恰恰是通过非基因组效应调节细胞增殖和分化。我们前期已证明促排卵引起的超生理剂量雌激素患者子宫内膜上的雌激素膜受体Gper表达下调,并伴随内膜容受性的降低,提示Gper介导的非基因组效应会调节内膜对胚胎的接受能力。随后对RIF患者的研究显示其内膜上Gper表达显著下调，提示Gper对RIF患者内膜的增殖准备起关键作用。据此我们首次提出RIF发生的分子机制:子宫内膜上Gper表达下调,使内膜细胞对雌激素的应答受到抑制,影响内膜增殖及种植潜能,最终导致RIF的发生。本项目旨在获得Gper对雌激素的应答异常导致RIF患者内膜增殖不足的直接证据,为临床治疗RIF提供更充分的科学依据。

最近发现子内膜增殖不充分是反复种植失败(RIF)的主要原因,并证实RIF患者内膜上雌激素核受体及其介导的基因组效应元件显著下调。然而,最先应答雌激素的膜受体Gper一直被忽略,其作用恰恰是通过非基因组效应调节细胞增殖和分化。我们前期已证明促排卵引起的超生理剂量雌激素患者子宫内膜上的雌激素膜受体Gper表达下调,并伴随内膜容受性的降低,提示Gper介导的非基因组效应会调节内膜对胚胎的接受能力。随后对RIF患者的研究显示其内膜上Gper表达显著下调，提示Gper对RIF患者内膜的增殖准备起关键作用。据此我们首次提出RIF发生的分子机制:子宫内膜上Gper表达下调,使内膜细胞对雌激素的应答受到抑制,影响内膜增殖及种植潜能,最终导致RIF的发生。本项目旨在获得Gper对雌激素的应答异常导致RIF患者内膜增殖不足的直接证据,为临床治疗RIF提供更充分的科学依据。