Global analysis of differential luminal epithelial gene expression at mouse implantation sites
Global analysis of differential luminal epithelial gene expression at mouse implantation sites
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小鼠植入部位差异管腔上皮基因表达的整体分析。
DOI：
10.1677/jme.1.02009
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发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
Yang, Zeng-Ming
中科院分区：
文献类型：
--
作者：
Chen, Ying;Ni, Hua;Yang, Zeng-Ming
尽管不同物种的着床类型不同，但胚泡滋养外胚层与子宫上皮顶面之间的相互作用是着床过程中常见的事件。在这项研究中，通过酶消化法分离种植部位和植入间部位的子宫腔上皮，并用于基因芯片分析。在包含12 345个单基因的小鼠微阵列中，我们发现136个基因在植入部位上调了两倍以上，而223个基因至少下调了两倍。利用逆转录-聚合酶链式反应验证了从我们的芯片分析中随机选择的7个上调基因和6个下调基因的差异表达，表达趋势相似。通过原位杂交验证了8个上调基因的差异表达模式。与妊娠第5天着床部位和假孕第5天子宫相比，妊娠第5天着床部位的子宫腔上皮细胞上调了蛋白酶、丝氨酸、12神经胰蛋白酶、内皮素-1、γ-谷氨酰水解酶、RAS同源基因家族成员U、T细胞免疫球蛋白和含有2的粘蛋白结构域、3-单氧合酶/色氨酸5-单氧酶激活蛋白、γ-多肽和半胱氨酸富含蛋白61(Cyr61)。这些基因可能与胚胎着床过程中胚胎的附着和粘连有关。以着床点上调的基因Cyr61为研究对象，用原位杂交的方法检测其在围着床期的表达和调控。Cyr61在妊娠第4天午夜和第5天着床胚泡周围的腔上皮细胞和激活子宫中均有特异性表达，但在植入间点和延迟着床时未见表达，提示Cyr61在胚胎附着过程中可能参与了胚胎-子宫对话。我们的数据可能为未来胚胎着床的研究提供有价值的来源。
Although implantation types differ between species, the interaction between blastocyst trophectoderm and apical surface of the uterine epithelium is a common event during the implantation process. In this study, uterine luminal epithelium at implantation and inter-implantation sites was isolated by enzymatic digestion and used for microarray analysis. In a mouse microarray containing 12 345 unigenes, we found 136 genes upregulated more than twofold at the implantation site, while 223 genes were downregulated by at least twofold. Reverse transcription-PCR was used to verify the differential expression of seven upregulated and six downregulated genes chosen randomly from our microarray analysis, and the expression trends were similar. The differential expression patterns of eight upregulated genes were verified by in situ hybridization. Compared with the inter-implantation site on day 5 of pregnancy and the uterus on day 5 of pseudopregnancy, protease, serine, 12 neurotrypsin, endothelin-1, gamma-glutamyl hydrolase, Ras homolog gene family, member U, T-cell immunoglobulin, and mucin domain containing 2, proline-serine-threonine phosphatase-interacting protein 2, 3-monooxgenase/tryptophan 5-monooxgenase activation protein, gamma-polypeptide, and cysteine-rich protein 61 (Cyr61) were upregulated in the luminal epithelium at implantation site on day 5 of pregnancy. These genes may be related to embryo apposition and adhesion during embryo implantation. Cyr61, a gene upregulated at the implantation site, was chosen to examine its expression and regulation during the periimplantation period by in situ hybridization. Cyr61 mRNA was specifically localized in the luminal epithelium surrounding the implanting blastocyst at day 4 midnight and on day 5 of pregnancy, and in the activated uterus, but not expressed in inter-implantation sites and under delayed implantation, suggesting a role for Cyr61 in mediating embryonic-uterine dialog during embryo attachment. Our data could be a valuable source for future study on embryo implantation.