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Decidual Heparanase Activity Is Increased During Pregnancy in the Baboon (Papio anubis) and in In Vitro Decidualization of Human Stromal Cells¹

Departments of Chemistry and Biochemistry³ and Material Sciences,⁴ University of Delaware, Newark, Delaware 19716 Department of Obstetrics and Gynecology,⁵ University of Illinois, Chicago, Illinois 60612 Department of Obstetrics and Gyneacology,⁶ The Rosie Hospital, Cambridge CB2 2SW, United Kingdom Department of Pathology,⁷ University of Cambridge, Cambridge CB2 1QP, United Kingdom Department of Biological Sciences,⁸ University of Delaware, Newark, Delaware 19716

ABSTRACT

Implantation is a complex process involving interactions between the embryo and the uterus. Adhesion, remodeling of the maternal vasculature, and decidualization are crucial events necessary for successful implantation to occur. Heparanase (HPSE), an endo-β-D-glucuronidase, cleaves heparan sulfate at specific sites, leading to release of growth factors that may be involved in decidualization and remodeling of the maternal vasculature. HPSE also can function as a cell adhesion molecule. The aim of this study was to determine the expression of HPSE in the uteri of nonpregnant and pregnant baboons as well as in human stromal fibroblasts decidualized in vitro. We examined the localization and expression of HPSE using immunohistochemistry, Western blotting, RT-PCR, and activity assays. In nonpregnant baboon uteri, HPSE expression was localized to the apical surface of the glandular epithelia and in glandular secretions. However, in pregnant baboon uteri, HPSE was localized primarily in decidua. Uteri obtained at midpregnancy had higher heparanase activity compared with the nonpregnant uteri. A slight increase in HPSE expression was observed in human stromal fibroblasts decidualized in vitro. HPSE and HPSE2 mRNA transcripts were present in both decidualized tissue and cells. Increases in heparanase activity in the decidua from pregnant baboon uteri compared with tissue from nonpregnant animals and in human stromal fibroblasts decidualized in vitro suggest that HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation.

heparanase, implantation, in vitro human decidualization, primate

¹Supported by National Institutes of Health grants HD25235 (D.D.C. and M.C.F.-C.) and HD42280 (A.T.F).

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