Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity.
Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity.
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DOI：
10.1016/j.devcel.2011.09.010
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发表时间：
2011-12-13
影响因子：
11.8
通讯作者：
Dey SK
中科院分区：
文献类型：
--
作者：
Daikoku T;Cha J;Sun X;Tranguch S;Xie H;Fujita T;Hirota Y;Lydon J;DeMayo F;Maxson R;Dey SK
在有着床能力的胚泡和接受子宫之间进行有效的双向交流是哺乳动物繁殖的先决条件。只有当这种分子串扰建立时，胚泡才会被植入。在这里，我们展示了肌肉片段同源框基因(MSH)家族成员Msx1和MSX2，这两个高度保守的基因在发育过程中对上皮-间充质相互作用至关重要，在胚胎着床中也起着至关重要的作用。Msx1/Msx2的表达缺失与子宫腔上皮细胞极性改变有关，并通过调控Wnt5a的表达影响E-钙粘素/β-连环蛋白复合体的形成。Wnt5a体外应用可抑制子宫上皮细胞的胚泡侵袭和滋养层生长。Msx1/MSX2基因对赋予子宫容受性和植入准备能力至关重要，这一发现可能具有临床意义，因为子宫容受性受损是试管受精项目中妊娠失败的主要原因。
An effective bidirectional communication between an implantation-competent blastocyst and the receptive uterus is a prerequisite for mammalian reproduction. The blastocyst will implant only when this molecular cross-talk is established. Here we show that the muscle segment homeobox gene (Msh) family members Msx1 and Msx2, which are two highly conserved genes critical for epithelial-mesenchymal interactions during development, also play crucial roles in embryo implantation. Loss of Msx1/Msx2 expression correlates with altered uterine luminal epithelial cell polarity and affects E-cadherin/β-catenin complex formation through the control of Wnt5a expression. Application of Wnt5a in vitro compromised blastocyst invasion and trophoblast outgrowth on cultured uterine epithelial cells. The finding that Msx1/Msx2 genes are critical for conferring uterine receptivity and readiness to implantation could have clinical significance, because compromised uterine receptivity is a major cause of pregnancy failure in IVF programs.
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