Abstract:
:Angiogenic factors, including vascular endothelial growth factor (VEGF), are expressed during follicular development. Our objective was to investigate the role of VEGF in the early follicular phase to test whether early cyclic follicle development and selection are angiogenesis-dependent processes. After documentation of two normal ovulatory cycles, female rhesus monkeys (n = 6) received five iv injections of anti-VEGF receptor 2 (anti-VEGF-R2) antibody at 3-d intervals starting on cycle d 2-4. To evaluate nonspecific effects of the treatment antibody, all monkeys also received iv injections of nonspecific humanized mouse IgG, using an identical regimen. Daily measurements of FSH, LH, estradiol, and progesterone were obtained, throughout the entire period, to monitor cyclicity. Administration of anti-VEGF-R2 antibody resulted in a significant decline in mean inhibin B levels [control, 181.0 +/- 29.6 (mean +/- SE); treatment d 2, 44.5 +/- 13.1 pg/ml; P < 0.05]. No decrease was observed after IgG treatment. Anti-VEGF-R2 antibody treatment also delayed the first significant increase in estradiol and lengthened the follicular phase from 10-12 d in the preceding two control cycles to 20-42 d in treatment cycles. FSH and LH concentrations increased significantly, within 24 h after anti-VEGF-R2 antibody treatment, to levels 2-2.5 times over controls. Our results demonstrate that anti-VEGF-R2 antibody therapy in the early follicular phase interferes with the normal development of the cohort of recruited antral follicles. The data clearly indicate that the recruitment-selection process of follicles in the early follicular phase in the nonhuman primate is controlled by VEGF, through the VEGF-R2.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Zimmermann RC,Xiao E,Bohlen P,Ferin Mdoi
10.1210/endo.143.7.8896subject
Has Abstractpub_date
2002-07-01 00:00:00pages
2496-502issue
7eissn
0013-7227issn
1945-7170journal_volume
143pub_type
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