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Heparanase Expression and Function During Early Pregnancy in Mice¹

Departments of Chemistry and Biochemistry,³ Biological Sciences,⁴ and Materials Sciences,⁵ and the Center for Translational Cancer Research,⁶ University of Delaware, Newark, Delaware 19716 Division of Reproductive and Developmental Biology,⁷ Vanderbilt University Medical Center, Nashville, Tennessee 37232

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 support cell adhesion. Heparanase (HPSE) is an endo-beta-glucuronidase that cleaves HS at specific sites. HPSE also can act as an adhesion molecule independent of its catalytic activity. Thus, HPSE is a multifunctional molecule contributing to and modulating HS-dependent processes. Exogenously added HPSE improves embryo implantation in mice; however, no information is available regarding the normal pattern of HPSE 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 HPSE 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 HPSE activity was characterized and demonstrated to increase >40-fold during early pregnancy. Finally, we demonstrate that the HPSE inhibitor PI-88 severely inhibits embryo implantation in vivo. Collectively, these results indicate that HPSE plays a role in blastocyst implantation and complements previous studies showing a role for HS-dependent interactions in this process.

decidua, embryo, endometrium, heparanase, implantation, mice, pregnancy, trophoblast

¹This work was supported by the NIH grant HD25235 (D.D.C.) and Gynecologic Cancer Foundation Award (T.D.).

Correspondence: ²FAX: 302 831 2281; e-mail: dcarson{at}udel.edu

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]