Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats.
Two endometrial vascular events, increased permeability and endothelial cell proliferation, characterize the early stages of embryo implantation in rats. Vascular endothelial growth factor (VEGF), a heparin-binding homodimeric glycoprotein, is expressed in the uterus at the time of implantation. The aim of this study was to investigate the effects of systemic administration of blocking antibody to VEGF on endometrial vascular permeability and endothelial cell proliferation around the time of embryo implantation in rats. Rats were injected i.p. with 1.0, 0.8 or 0.6 ml of anti-VEGF antibody or control serum on day 3 of pregnancy and Evans blue dye was administered i.v. on day 5 of pregnancy. The number of implantation sites (blue bands along the uterus) was counted and endothelial cell proliferation was identified using double staining immunohistochemistry. The number of blue bands was significantly lower (P < 0.05) after injection of 1.0 ml blocking antibody (1.8 +/- 1.56) compared with that in control rats (11.6 +/- 1.97). The number of blue bands was significantly different among rats injected with 1.0 (1.8 +/- 1.56), 0.8 (6.0 +/- 3.67) or 0.6 (10.7 +/- 0.33) ml anti-VEGF antibody, indicating a concentration effect of anti-VEGF antibody. No significant differences in endothelial cell proliferation at embryo implantation sites were observed after injection with anti-VEGF antibody or control serum. At intersites (uterine zones between the blue bands), injection of 0.6 ml anti-VEGF antibody caused a significant reduction (P < 0.05) in the percentage of vessels with proliferating endothelial cells (7.25 +/- 2.39%), with a non-significant reduction using 1.0 or 0.8 ml anti-VEGF antibody. No significant differences in microvascular density at either embryo implantation sites or intersites were observed between rats injected with anti-VEGF antibody or control serum. In conclusion, VEGF is the main factor responsible for increased endometrial vascular permeability at implantation. It may regulate endometrial endothelial cell proliferation before implantation and at intersites, thus indicating that factors or mechanisms other than VEGF may regulate endothelial cell proliferation at the site of implantation.
Rabbani
M L
ML
Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Rogers
P A
PA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002199:Capillary Permeability; D002455:Cell Division; D010064:Embryo Implantation; D004717:Endometrium / Q000098:blood supply* / Q000166:cytology; D016228:Endothelial Growth Factors / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007150:Immunohistochemistry; D008222:Lymphokines / Q000276:immunology / Q000502:physiology*; D008833:Microcirculation / Q000033:anatomy & histology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors