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PMID: 12952915 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 112 ·No. 5 ·2003-09-00 ·Pages 659-69

Zimmermann RC, Hartman T, Kavic S, Pauli SA, Bohlen P, Sauer MV, Kitajewski J

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.

MeSH Terms
Animals Cell Division Endothelial Growth Factors/physiology Estradiol/biosynthesis Female Gonadotropins, Equine/pharmacology Hypophysectomy Intercellular Signaling Peptides and Proteins/physiology Lymphokines/physiology Mice Neovascularization, Physiologic Ovarian Follicle/blood supply,growth & development Progesterone/biosynthesis Rats Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2/physiology Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Gonadotropins, Equine Intercellular Signaling Peptides and Proteins Lymphokines Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Progesterone Estradiol Vascular Endothelial Growth Factor Receptor-2
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zimmermann Ralf C
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. rcz3@columbia.edu
Hartman Tipton
Kavic Suzanne
Pauli Samuel A
Bohlen Peter
Sauer Mark V
Kitajewski Jan
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI18740
Email
rcz3@columbia.edu
Published
2003-09-00
Pages
659-69
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC182212
Subset
IM
Grants
NICHD NIH HHS · K12 HD001275 · United States
NHLBI NIH HHS · R01 HL062454 · United States
NHLBI NIH HHS · HL-62454 · United States
NICHD NIH HHS · K12 HD-01275 · United States
External Links
PubMed source DOI: 10.1172/JCI18740 PMC Full Text View journal details
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