Vascular endothelial growth factor receptor 2-mediated angiogenesis is essential for gonadotropin-dependent follicle development
Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and fu...
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Published in | The Journal of clinical investigation Vol. 112; no. 5; pp. 659 - 669 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Clinical Investigation
01.09.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and function of preovulatory follicles as demonstrated by histological analysis or hormone measurements. Blockage of function of VEGF receptor 2 (VEGFR-2) alters follicular hormone secretion, suggesting that the intraovarian effect of VEGF might be mediated by this receptor. The specific mechanism by which follicular development was blocked in these previous studies remains unclear, however. Here we characterize the intraovarian role of VEGFR-2 activity on follicular development by choosing a model in which active feedback is absent, the prepuberally hypophysectomized mouse. Hypophysectomy prevents advanced follicle growth and maturation; however, follicle development to the preovulatory stage can be stimulated by administration of gonadotropins. We report that exogenously administered gonadotropins are unable to drive follicle development to the preovulatory stage in the presence of antiangiogenic agent, VEGFR-2-neutralizing Ab's. This inhibition of follicular development is caused by arrests to both angiogenesis and antrum formation. We conclude that the intraovarian VEGF/VEGFR-2 pathway is critical for gonadotropin-dependent angiogenesis and follicular development. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Address correspondence to: Ralf C. Zimmermann, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA. Phone: (212) 305-8693; Fax: (212) 305-3869; E-mail: rcz3@columbia.edu. |
ISSN: | 0021-9738 1558-8238 |
DOI: | 10.1172/jci200318740 |