Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Biol Reprod. 2011 Nov;85(5):996-1004. doi: 10.1095/biolreprod.110.090126. Epub 2011 Jul 13.
The adherens junction (AJ) is important for maintaining uterine structural integrity, composition of the luminal environment, and initiation of implantation by virtue of its properties of cell-cell recognition, adhesion, and establishment of cell polarity and permeability barriers. In this study, we investigated the uterine changes of AJ components E-cadherin, beta-catenin, and alpha-catenin at their mRNA and protein levels, together with the cellular distribution of meprinbeta, phospho-beta-catenin, and active beta-catenin proteins, in hamsters that show only ovarian progesterone-dependent uterine receptivity and implantation. By in situ hybridization and immunofluorescence, we have demonstrated that uterine epithelial cells expressed three of these AJ proteins and their mRNAs prior to and during the initial phase of implantation. Immunofluorescence study showed no change in epithelial expression patterns of uterine AJ proteins from Days 1 to 5 of pregnancy. With advancement of the implantation process, AJ components were primarily expressed in cells of the secondary decidual zone (SDZ), but not in the primary decidual zone (PDZ). In contrast, we noted strong expression of beta-catenin and alpha-catenin proteins in the PDZ, but not in the SDZ, of mice. Taken together, these results suggest that AJ proteins contribute to uterine barrier functions by cell-cell adhesion to ensure protection of the embryo. In addition, cleavage of E-cadherin by meprinbeta might contribute to weakening uterine epithelial cell-cell contact for blastocyst implantation. We also report that the nuclear localization of active beta-catenin from Day 4 onward in hamsters implies that beta-catenin/Wnt-signal transduction is activated in the uterus during implantation and decidualization.
黏着连接(AJ)对于维持子宫结构的完整性、腔环境的组成以及通过细胞识别、黏附和建立细胞极性和通透性屏障来启动着床都非常重要。在这项研究中,我们研究了黏着连接成分 E-钙黏蛋白、β-连环蛋白和α-连环蛋白在 mRNA 和蛋白水平上的子宫变化,以及在仅表现出卵巢孕激素依赖性子宫接受性和着床的仓鼠中,meprinbeta、磷酸化β-连环蛋白和活性β-连环蛋白蛋白的细胞分布。通过原位杂交和免疫荧光,我们已经证明,在着床的初始阶段之前和期间,子宫上皮细胞表达了这三种 AJ 蛋白及其 mRNA。免疫荧光研究表明,妊娠第 1 至 5 天,上皮细胞的 AJ 蛋白表达模式没有变化。随着着床过程的进展,AJ 成分主要在次级蜕膜区(SDZ)的细胞中表达,但不在初级蜕膜区(PDZ)中表达。相比之下,我们注意到在 PDZ 中强烈表达β-连环蛋白和α-连环蛋白蛋白,但在 SDZ 中不表达。总的来说,这些结果表明 AJ 蛋白通过细胞间黏附对子宫屏障功能做出贡献,以确保对胚胎的保护。此外,E-钙黏蛋白被 meprinbeta 切割可能有助于削弱胚胎植入时的子宫上皮细胞间接触。我们还报告说,从第 4 天开始,仓鼠子宫中活性β-连环蛋白的核定位意味着β-连环蛋白/Wnt 信号转导在着床和蜕膜化期间在子宫中被激活。