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Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Ralf C. Zimmermann; Tipton Hartman; Suzanne M. Kavic; Samuel A. Pauli; Peter Bohlen; Mark V. Sauer; Jan K. Kitajewski

Title:
Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development
Author(s):
Zimmermann, Ralf C.
Hartman, Tipton
Kavic, Suzanne M.
Pauli, Samuel A.
Bohlen, Peter
Sauer, Mark V.
Kitajewski, Jan K.
Date:
Type:
Articles
Department:
Obstetrics and Gynecology
Volume:
112
Permanent URL:
Book/Journal Title:
Journal of Clinical Investigation
Abstract:
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.
Subject(s):
Developmental biology
Publisher DOI:
http://dx.doi.org/10.1172/JCI200318740
Item views:
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Metadata:
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