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1 July 2005 Spatiotemporal Expression of Heparanase During Human and Rodent Ovarian Folliculogenesis
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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.

Ronit Haimov-Kochman, Diana Prus, Eyal Zcharia, Debra S. Goldman-Wohl, Shira Natanson-Yaron, Caryn Greenfield, Eyal Y. Anteby, Reuven Reich, Joseph Orly, Alex Tsafriri, Arye Hurwitz, Israel Vlodavsky, and Simcha Yagel "Spatiotemporal Expression of Heparanase During Human and Rodent Ovarian Folliculogenesis," Biology of Reproduction 73(1), 20-28, (1 July 2005).
Received: 2 October 2004; Accepted: 1 February 2005; Published: 1 July 2005

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