Nie G Y, Li Y, Hampton A L, Salamonsen L A, Clements J A, Findlay J K
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Mol Reprod Dev. 2000 Apr;55(4):351-63. doi: 10.1002/(SICI)1098-2795(200004)55:4<351::AID-MRD1>3.0.CO;2-L.
Successful implantation requires synchronous development of and active dialogue between the maternal endometrium and the implanting blastocyst. While it is well established that appropriate maternal steroid hormones are essential for endometrial preparation for implantation, the molecular events at the actual site of implantation are still little understood. The aims of our studies were to identify genes explicitly expressed or repressed at the sites of implantation by utilising RNA differential display (DDPCR), and to establish the roles of these genes in the implantation process in a mouse model. Ten bands unique in implantation sites compared to interimplantation sites were identified by DDPCR and subsequently confirmed by Northern blotting. One of these bands contained a cDNA fragment that was highly homologous to mouse monoclonal nonspecific suppressor factor beta (MNSFbeta) or Fau. The full cDNA sequence of this gene, obtained by screening a lambdagt11 cDNA library, was essentially the same as MNSFbeta, except that it had much longer 5' untranslated region. Interestingly, both Northern and immunohistochemical analysis showed that the expression of this gene was much lower in implantation sites compared to interimplantation sites on day 4.5 of pregnancy, when embryos first attach to the uterus and initiate implantation, and on day 5.5, when implantation has advanced. These results suggest a role for MNSF during implantation and early pregnancy, possibly through regulating the proliferation and/or differentiation of uterine stromal cells. It may also be involved in the selective production of TH2-type cytokines in implantation sites to regulate the immune system at the maternal-fetal interface.
成功着床需要母体子宫内膜与着床囊胚之间同步发育并进行活跃对话。虽然众所周知,适当的母体类固醇激素对于子宫内膜为着床做准备至关重要,但着床实际部位的分子事件仍知之甚少。我们研究的目的是利用RNA差异显示(DDPCR)来鉴定在着床部位特异性表达或抑制的基因,并在小鼠模型中确定这些基因在着床过程中的作用。通过DDPCR鉴定出与非着床部位相比在着床部位独特的10条条带,随后通过Northern印迹法进行了确认。其中一条条带包含一个与小鼠单克隆非特异性抑制因子β(MNSFβ)或Fau高度同源的cDNA片段。通过筛选λgt11 cDNA文库获得的该基因的完整cDNA序列与MNSFβ基本相同,只是其5'非翻译区长得多。有趣的是,Northern分析和免疫组织化学分析均显示,在妊娠第4.5天(此时胚胎首次附着于子宫并开始着床)和第5.5天(此时着床已推进),与非着床部位相比,该基因在着床部位的表达要低得多。这些结果表明MNSF在着床和早期妊娠过程中发挥作用,可能是通过调节子宫基质细胞的增殖和/或分化。它也可能参与着床部位TH2型细胞因子的选择性产生,以调节母胎界面的免疫系统。