Developmental Cell
Volume 21, Issue 6, 13 December 2011, Pages 1014-1025
Journal home page for Developmental Cell

Article
Conditional Deletion of MSX Homeobox Genes in the Uterus Inhibits Blastocyst Implantation by Altering Uterine Receptivity

https://doi.org/10.1016/j.devcel.2011.09.010Get rights and content
Under an Elsevier user license
open archive

Summary

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.

Highlights

► Uterine deletion of Msx genes leads to implantation failure and infertility ► Msx1/Msx2 deficiency results in altered epithelial cell integrity ► Msx1/Msx2 deficiency upregulates uterine levels of Wnt5a ► Wnt5a facilitates E-cadherin/β-catenin complex formation in luminal epithelial cells

Cited by (0)

4

These authors contributed equally to this work