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BOR - Papers in Press, published online ahead of print February 23, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.036780
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BIOLOGY OF REPRODUCTION 73, 20–28 (2005)
DOI: 10.1095/biolreprod.104.036780
© 2005 by the Society for the Study of Reproduction, Inc.

Spatiotemporal Expression of Heparanase During Human and Rodent Ovarian Folliculogenesis1

Ronit Haimov-Kochman 3, Diana Prus 4, Eyal Zcharia 5, Debra S. Goldman-Wohl 3, Shira Natanson-Yaron 3, Caryn Greenfield 3, Eyal Y. Anteby 3, Reuven Reich 6, Joseph Orly 7, Alex Tsafriri 8, Arye Hurwitz 3, Israel Vlodavsky 2 9, and Simcha Yagel 3

Departments of Obstetrics and Gynecology,3 Pathology,4 Oncology,5 Hadassah University Medical Center, Jerusalem 91240, Israel Department of Clinical Pharmacology,6 The Hebrew University, Jerusalem 91120, Israel Department of Biological Chemistry,7 The Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel Department of Biological Regulation,8 Weizmann Institute of Science, Rehovot 76100, Israel The Cancer and Vascular Biology Research Center,9 The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs), major components of the basement membrane (BM) and extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound molecules, including basic fibroblast growth factor (FGF2). Structural and functional development of the corpus luteum (CL) involves tissue remodeling, active angiogenesis, and steroid production. Heparanase-induced ECM and BM breakdown as well as FGF2-stimulated endothelial proliferation may have an important role in the regulation of luteal function. Heparanase mRNA was detected by reverse-transcription-polymerase chain reaction in granulosa cells recovered from follicular fluid of in vitro fertilization patients. Using sulfate-labeled ECM, heparanase enzymatic activity was determined in human luteinized granulosa cells. Employing immunohistochemistry, heparanase protein was localized predominantly in the theca interna cell layer of the mature antral follicle, whereas in human corpora lutea, both luteinized granulosa and theca cells were immunostained for heparanase. During luteolysis, heparanase was identified in macrophages surrounding the forming corpus albicans. In serially sectioned ovaries from unstimulated rats as well as from eCG-treated rats, expression of heparanase was noted exclusively in the ovarian steroid-producing interstitial tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in lutein cells of the forming corpora lutea. Temporal expression of heparanase in granulosa cells during the luteal phase and in macrophages during luteal regression supports the hypothesis that heparanase plays a role in human ovarian ECM remodeling and may potentiate cellular migration and growth factor bioavailability.

basic fibroblast growth factor, corpus luteum, follicle, granulosa cells, heparanase, ovary, theca cells


1 Supported by grants from the Hadassah Medical Organization for research of women's health, from the Israeli Ministry of Health, and from the Salzberg Research Foundation.

2 Correspondence: Israel Vlodavsky, Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, P.O. Box 9649, Haifa 31096, Israel. FAX: 972 4 8523947; Vlodavsk{at}cc.huji.ac.il




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