Human Endometrial CD98 Is Essential for Blastocyst Adhesion

Human Endometrial CD98 Is Essential for Blastocyst Adhesion
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DOI:
10.1371/journal.pone.0013380
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发表时间:
2010-10-15
期刊:
影响因子:
3.7
通讯作者:
Yanez-Mo, Maria
Yanez-Mo, Maria
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dominguez, Francisco;Simon, Carlos;Yanez-Mo, Maria

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背景:了解胚胎植入的分子基础具有重要的临床和生物学意义。目前所知甚少的粘附受体,确定子宫内膜容受性胚胎implantation in human.Methods和主要发现:使用两个人子宫内膜细胞系的特点是低和高的容受性,我们确定了膜受体CD 98作为一种新的分子选择性和显着相关的接受表型。在人子宫内膜样品中,CD 98是唯一研究的分子,其表达仅限于人子宫内膜组织中的着床窗。CD 98的表达仅限于顶端表面,并包括在四跨膜蛋白富集的微域的原代子宫内膜上皮细胞,证明了CD 98和四跨膜蛋白CD 9之间的生化关联。通过用人绒毛膜促性腺激素、17-β-雌二醇、LIF或EGF处理原代子宫内膜上皮细胞,在体外诱导CD 98表达。子宫内膜过度表达的CD 98或四跨膜蛋白CD 9大大增强小鼠胚泡粘附,而它们的siRNA介导的消耗降低了胚泡adhesion rate.Conclusions:这些结果表明,CD 98,四跨膜蛋白富集的微结构域的一个组成部分,似乎是一个重要的决定因素,人子宫内膜容受性在植入窗口。
Background: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans.Methods and Principal Findings: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-beta-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate.Conclusions: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window.