Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation

FASEB J. 2016 Apr;30(4):1425-35. doi: 10.1096/fj.15-282798. Epub 2015 Dec 14.


Embryo implantation requires that the uterus differentiate into the receptive state. Failure to attain uterine receptivity will impede blastocyst attachment and result in a compromised pregnancy. The molecular mechanism by which the uterus transitions from the prereceptive to the receptive stage is complex, involving an intricate interplay of various molecules. We recently found that mice with uterine deletion ofMsxgenes (Msx1(d/d)/Msx2(d/d)) are infertile because of implantation failure associated with heightened apicobasal polarity of luminal epithelial cells during the receptive period. However, information on Msx's roles in regulating epithelial polarity remains limited. To gain further insight, we analyzed cell-type-specific gene expression by RNA sequencing of separated luminal epithelial and stromal cells by laser capture microdissection fromMsx1(d/d)/Msx2(d/d)and floxed mouse uteri on d 4 of pseudopregnancy. We found that claudin-1, a tight junction protein, and small proline-rich (Sprr2) protein, a major component of cornified envelopes in keratinized epidermis, were substantially up-regulated inMsx1(d/d)/Msx2(d/d)uterine epithelia. These factors also exhibited unique epithelial expression patterns at the implantation chamber (crypt) inMsx1(f/f)/Msx2(f/f)females; the patterns were lost inMsx1(d/d)/Msx2(d/d)epithelia on d 5, suggesting important roles during implantation. The results suggest thatMsxgenes play important roles during uterine receptivity including modulation of epithelial junctional activity.-Sun, X., Park, C. B., Deng, W., Potter, S. S., Dey, S. K. Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation.

Keywords: Sprr2; adhesion; claudin; receptivity; uterus.

Publication types

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

MeSH terms

  • Animals
  • Claudin-1 / genetics*
  • Claudin-1 / metabolism
  • Cornified Envelope Proline-Rich Proteins / genetics
  • Cornified Envelope Proline-Rich Proteins / metabolism
  • Embryo Implantation*
  • Epithelial Cells / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Ontology
  • Gene Regulatory Networks / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • MSX1 Transcription Factor / genetics*
  • MSX1 Transcription Factor / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterus / metabolism*


  • Claudin-1
  • Cornified Envelope Proline-Rich Proteins
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • MSX2 protein
  • Msx1 protein, mouse
  • Sprr2a1 protein, mouse