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

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 of Msx genes ( 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 from Msx1 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 in Msx1 d/d /Msx2 d/d uterine epithelia. These factors also exhibited unique epithelial expression patterns at the implantation chamber (crypt) in Msx1 f/f /Msx2 f/f females; the patterns were lost in Msx1 d/d /Msx2 d/d epithelia on d 5, suggesting important roles during implantation. The results suggest that Msx genes 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. FASEB J. 30, 1425–1435 (2016). www.fasebj.org