Inactivation of nuclear Wnt- (cid:2) -catenin signaling limits blastocyst competency for implantation
Inactivation of nuclear Wnt- (cid:2) -catenin signaling limits blastocyst competency for implantation
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发表时间：
2008
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通讯作者：
Huirong Xie;S. Tranguch;Xiangxu Jia;H. Zhang;S. Das;S. Dey;C. Kuo;Haibin Wang
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作者：
Huirong Xie;S. Tranguch;Xiangxu Jia;H. Zhang;S. Das;S. Dey;C. Kuo;Haibin Wang
L从接受Empty或Dkk1ADV的孕妇眼眶后采血获得的血浆，使用抗His探针抗体(Santa Cruz Biotech)，如前所述(Kuhnert等人，2004年)。为了进一步探讨Wnt抑制胚泡着床的后果，我们应用了(Cid：2)-catenin-Tcf复合体的小分子抑制剂PKF115-584和CGP049090(诺华)(Lepourcelet)囊胚的激活是成功着床的先决条件。然而，胚泡激活的分子基础在很大程度上仍未被探索。结合分子、药理学和生理学方法，我们在这里表明，沉默小鼠的WNT-(CID：2)-连环蛋白信号不会对植入前胚胎到囊胚的发育和子宫容受性的准备产生不利影响，但值得注意的是，阻断了胚泡对着床的能力。利用生理相关的延迟着床模型和培养中的滋养层干细胞，我们进一步证明了规范的Wnt-(Cid：2)-catenin信号的协调激活和非规范的Wnt-RhoA信号通路的减弱确保了胚泡着床的能力。这些发现构成了新的证据，即Wnt信号是决定胚泡着床能力的至少一个途径。
l of plasma obtained by retroorbital phlebotomy from pregnant females receiving empty or Dkk1 ADV using anti-His probe antibody (Santa Cruz Biotechnology) as previously described (Kuhnert et al., 2004). To further explore the consequence of Wnt inhibition on blastocyst implantation, we applied small-molecule inhibitors of the (cid:2) -catenin-Tcf complex, PKF115-584 and CGP049090 (Novartis) (Lepourcelet The activation of the blastocyst, a process by which it gains competency to attach with the receptive uterus, is a prerequisite for successful implantation. However, the molecular basis of blastocyst activation remains largely unexplored. Combining molecular, pharmacological and physiological approaches, we show here that silencing of Wnt- (cid:2) -catenin signaling in mice does not adversely affect the development of preimplantation embryos to blastocysts and uterine preparation for receptivity, but, remarkably, blocks blastocyst competency to implantation. Using the physiologically relevant delayed implantation model and trophoblast stem cells in culture, we further demonstrate that a coordinated activation of canonical Wnt- (cid:2) -catenin signaling with attenuation of the non-canonical Wnt-RhoA signaling pathway ensures blastocyst competency to implantation. These findings constitute novel evidence that Wnt signaling is at least one pathway that determines blastocyst competency for implantation.