Zhang Ying, Peng Sha, Kuang Haibin, Chen Qi, Liu Shuang, Zhang Li, Duan Enkui
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
J Reprod Dev. 2009 Feb;55(1):17-22. doi: 10.1262/jrd.20043. Epub 2008 Aug 8.
Successful implantation depends on active dialogue between the maternal endometrium and the implanting blastocysts that is well controlled by groups of regulators at the molecular level. Dickkopf2 (Dkk2) is a member of Dickkopf family normally acting as an antagonist of canonical Wnt/beta-catenin signaling, which has been proven to participate in tumorigenesis and early embryo development. In order to explore the potential function of Dkk2 in embryo implantation, the present study investigated the uterine expression and regulation profiles of Dkk2 during periimplantation in mice. Using reverse transcription-polymerase chain reaction, immunohistochemistry and Western blotting, we showed that the mRNA and protein levels of Dkk2 began to increase in the glandular epithelium on day 4, continued to increase on day 5 and then decreased from day 6 of pregnancy. Moreover, on days 5-8 of pregnancy, Dkk2 was increasingly expressed in the deciduum of the uterus, especially around the implanting embryos. In addition, upregulation of Dkk2 was also observed in uteri treated with estrogen (estradiol-17beta) as well as in oil-induced artificial decidualization, indicating that the expression of Dkk2 could be induced by both steroid hormone (estrogen) and the process of decidualization. Furthermore, in the postimplantation uterus, the Dkk2 protein showed an inversed expression with active beta-catenin from day 6 onward, supporting the notion that Dkk2 plays an inhibitory role against canonical Wnt signaling in the context of the decidualizing stroma. Collectively, our data suggests that Dkk2 expression is associated with uterine receptivity changes as well as the process of decidualization and that it might play important roles through inhibition of canonical Wnt signaling in the periimplantation uterus.
成功着床依赖于母体子宫内膜与着床囊胚之间的活跃对话，这种对话在分子水平上受到多组调节因子的良好调控。Dickkopf2（Dkk2）是Dickkopf家族的一员，通常作为经典Wnt/β-连环蛋白信号通路的拮抗剂，已被证明参与肿瘤发生和早期胚胎发育。为了探究Dkk2在胚胎着床中的潜在功能，本研究调查了小鼠围着床期子宫中Dkk2的表达及调控情况。通过逆转录-聚合酶链反应、免疫组织化学和蛋白质印迹法，我们发现，妊娠第4天，Dkk2的mRNA和蛋白水平在腺上皮中开始升高，第5天持续升高，然后从妊娠第6天开始下降。此外，在妊娠第5-8天，Dkk2在子宫蜕膜中表达逐渐增加，尤其是在着床胚胎周围。另外，在用雌激素（17β-雌二醇）处理的子宫以及油诱导的人工蜕膜化子宫中也观察到Dkk2上调，表明Dkk2的表达可被甾体激素（雌激素）和蜕膜化过程诱导。此外，在着床后子宫中，从第6天起，Dkk2蛋白与活性β-连环蛋白呈反向表达，支持了Dkk2在蜕膜化基质背景下对经典Wnt信号通路起抑制作用的观点。总体而言，我们的数据表明，Dkk2的表达与子宫接受性变化以及蜕膜化过程相关，并且它可能通过抑制围着床期子宫中的经典Wnt信号通路发挥重要作用。
