Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity

Dev Cell. 2011 Dec 13;21(6):1014-25. doi: 10.1016/j.devcel.2011.09.010. Epub 2011 Nov 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity / genetics
  • Cell Polarity / physiology
  • Embryo Implantation / drug effects
  • Embryo Implantation / genetics*
  • Embryo Implantation / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Female
  • Fertility / genetics
  • Fertility / physiology
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Leukemia Inhibitory Factor / administration & dosage
  • Leukemia Inhibitory Factor / deficiency
  • Leukemia Inhibitory Factor / genetics
  • MSX1 Transcription Factor / deficiency
  • MSX1 Transcription Factor / genetics*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Pregnancy
  • Pregnancy Outcome
  • Uterus / cytology
  • Uterus / metabolism*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • Wnt-5a Protein
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Homeodomain Proteins
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • MSX1 Transcription Factor
  • MSX2 protein
  • Msx1 protein, mouse
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • beta Catenin