Vascular endothelial growth factor is essential for corpus luteum angiogenesis.
The development and endocrine function of the ovarian corpus luteum (CL) are dependent on the growth of new capillary vessels. Although several molecules have been implicated as mediators of CL angiogenesis, at present there is no direct evidence for the involvement of any. Here we report the unexpected finding that treatment with truncated soluble Flt-1 receptors, which inhibit vascular endothelial growth factor (VEGF) bioactivity, resulted in virtually complete suppression of CL angiogenesis in a rat model of hormonally induced ovulation. This effect was associated with inhibition of CL development and progesterone release. Failure of maturation of the endometrium was also observed. Areas of ischemic necrosis were demonstrated in the corpora lutea (CLs) of treated animals. However, no effect on the preexisting ovarian vasculature was observed. These findings demonstrate that, in spite of the redundancy of potential mediators, VEGF is essential for CL angiogenesis. Furthermore, they have implications for the control of fertility and the treatment of ovarian disorders characterized by hypervascularity and hyperplasia.
Ferrara
N
N
Department of Cardiovascular Research, Genentech Inc., South San Francisco, California 94080, USA. Ferrara.Napoleone@gene.com
Chen
H
H
Davis-Smyth
T
T
Gerber
H P
HP
Nguyen
T N
TN
Peers
D
D
Chisholm
V
V
Hillan
K J
KJ
Schwall
R H
RH
D000818:Animals; D003338:Corpus Luteum / Q000033:anatomy & histology / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D006062:Gonadotropins / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D014599:Uterus / Q000033:anatomy & histology; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006062:Gonadotropins; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1