Blastocyst-dependent upregulation of metalloproteinase/disintegrin MDC9 expression in rabbit endometrium

Abstract 

Blastocyst attachment to mammalian uteri at implantation involves the adhesion of the trophoblast to the uterine epithelial surface. In the rabbit, fusion between adjacent epithelial cells precedes the initial attachment phase and is followed by fusion between the trophoblast and the epithelium. The reverse transcription/polymerase chain reaction method has been used to prepare a partial cDNA (rbMDC9) from periimplantation-stage endometrium; this represents the rabbit ortholog of MDC9, a member of the cellular metalloproteinase/disintegrin (ADAM) gene family. We demonstrate here the reproductive stage-specific expression of rbMDC9 mRNA in uterine epithelium during the periimplantation period. Furthermore, this expression is upregulated at implantation sites, and in situ hybridization analysis has revealed that the epithelial cells with the most prominent signal are those apposed to blastocysts. Immunostaining with E-cadherin has been used to trace lateral membranes of epithelial cells and, together with nuclear staining, has enabled the identification of cells fusing to become multinucleated cells, and later, to become an epithelial syncytium (symplasma). These fusing cells express the highest level of rbMDC9 mRNA. The results suggest that MDC9, a transmembrane modular protein with domains having potential integrin-binding, metalloproteinase, and fusogenic functions, is probably critical for the cellular interactions accompanying blastocyst implantation.