Knockdown of the tetraspan protein epithelial membrane protein-2 inhibits implantation in the mouse
Knockdown of the tetraspan protein epithelial membrane protein-2 inhibits implantation in the mouse
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DOI：
10.1016/j.ydbio.2006.01.015
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发表时间：
2006-04-15
影响因子：
2.7
通讯作者：
Williams, CJ
中科院分区：
文献类型：
--
作者：
Wadehra, M;Dayal, M;Williams, CJ
妊娠的建立需要胚泡期胚胎的滋养外胚层细胞与子宫内膜细胞之间成功的分子相互作用。这些相互作用是复杂的，需要同步发展和协调的内分泌、旁分泌和自分泌沟通。在这项研究中，我们证明了Tetraspan蛋白上皮膜蛋白-2(EMP2)参与了植入过程中的这些分子相互作用。EMP2在子宫中高表达，在着床窗期从子宫内膜上皮细胞内移位到顶端，在蜕膜间质细胞中表达。我们开发了利用核酶或短发夹状RNA介导的机制来靶向破坏子宫内膜EMP2 mRNA的质粒构建。利用体内生殖道基因转移技术，将这些构建物在怀孕第一天导入小鼠子宫。与对照组相比，任一种方法降低EMP2表达均可显著减少子宫角内植入部位的数量。这些研究表明，Tetraspan蛋白在着床中的功能以前是未知的，并可能为开发避孕和生育的治疗方法提供一个分子框架。(C)2006 Elsevier Inc.保留所有权利。
The establishment of pregnancy requires a successful molecular interaction between the trophectoderm cells of the blastocyst stage embryo and the endometrial cells of the uterus. These interactions are complex and require synchronous development and coordinated endocrine, paracrine, and autocrine communication. In this study, we demonstrate that the tetraspan protein epithelial membrane protein-2 (EMP2) is involved in these molecular interactions during implantation. EMP2, which is highly expressed in the uterus, translocates from an intracellular location to the apical surface of the endometrial epithelium during the window of implantation and is expressed in decidualized stromal cells. We developed plasmid constructs that utilized either ribozyme-mediated or short hairpin RNA-mediated mechanisms to target endometrial EMP2 mRNA for destruction. These constructs were transfected into the mouse uterus on day I of pregnancy using the technique of in vivo reproductive tract gene transfer. Reduction in EMP2 expression by either method resulted in a significant decrease in the number of implantation sites in the treated uterine horns as compared to control horns. These studies indicate a previously unknown function of tetraspan proteins in implantation and could provide a molecular framework for the development of therapeutic modalities for both contraception and fertility. (c) 2006 Elsevier Inc. All rights reserved.