Female Reproductive Tract

Heparanase Expression and Function During Early Pregnancy in Mice

Abstract
Embryo implantation is a complex process that involves interactions between cell surface and extracellular components of the blastocyst and the uterus including blastocyst adhesion to the uterine luminal epithelium, epithelial basement membrane penetration and stromal extracellular matrix remodeling, angiogenesis, and decidualization. These processes all involve interactions with heparan sulfate (HS) proteoglycans, which harbor various growth factors and cytokines and as support cell adhesion. Heparanase is an endo-beta-glucuronidase that cleaves HS at specific sites. Heparanase also can act as an adhesion molecule independent of its catalytic activity. Thus, heparanase is a multifunctional molecule contributing to and modulating HS-dependent processes. Exogenously added heparanase improves embryo implantation in mice; however, no information is available regarding the normal pattern of heparanase expression and activity during the implantation process in any system. Using several approaches, including real-time RT-PCR, in situ hybridization and immunohistochemistry, we determined that uterine heparanase expression increases dramatically during early pregnancy in mice. Heparanase mRNA and protein were primarily expressed in decidua and were rapidly induced at the implantation site. Uterine heparanase activity was characterized and demonstrated to increase > 40-fold during early pregnancy. Finally, we demonstrate that, the heparanase inhibitor, PI-88, severely inhibits embryo implantation in vivo. Collectively, these results indicate that heparanase plays a role in blastocyst implantation and complements previous studies showing a role for HS-dependent interactions in this process.

Key words: Embryo • Pregnancy • Decidua • Implantation • Trophoblast

This article has been cited by other articles:

				S. S D'Souza, A. T Fazleabas, P. Banerjee, J. R. A Sherwin, A. M Sharkey, M. C Farach-Carson, and D. D Carson Decidual Heparanase Activity Is Increased During Pregnancy in the Baboon (Papio anubis) and in In Vitro Decidualization of Human Stromal Cells Biol Reprod, February 1, 2008; 78(2): 316 - 323. [Abstract] [Full Text] [PDF]