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(587) THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN DOMINANT FOLLICLE SELECTION, EXPANSION, AND OVULATION IN THE MARMOSET. Taylor, Paul1, 2, Hillier, Steven2, Fraser, Hamish1, 2, 1 Medical Research Council, Edinburgh, UK2 University of Edinburgh Centre for Reproductive Biology, Edinburgh, UK ABSTRACT- Angiogenesis is essential for normal follicular development, and vascular endothelial growth factor (VEGF) has been shown to be intimately involved in follicular angiogenesis. VEGF has also been hypothesised to play a role in enhancing the permeability of the follicular vasculature, allowing movement of fluid into the developing follicles. To investigate the effect of inhibition of follicular angiogenesis during specific stages of follicle development in the marmoset (Callithrix jacchus) ovary we employed the VEGF TrapR1R2 (Regeneron Pharmaceuticals, Tarrytown, New York), recombinant protein comprising portions of the extracellular domains of human VEGFR1 and VEGFR2 fused to the Fc portion of human IgG. Timing of ovulation was synchronised by administration of prostaglandin in the previous luteal phase. VEGF Trap (25 mg/kg S.C.) or vehicle was administered on either Day 0 (n=3) or Day 5 (n=5) of the follicular phase, and ovaries collected on follicular Day 10, the predicted time of ovulation. All ovaries were serial sectioned for analysis. Cell proliferation was assessed by ICC localisation of bromo-deoxyuridine and the extent of vascularisation by ICC localisation of CD31. Ovaries from control (n=7) marmosets had 2 or 3 preovulatory follicles or newly formed corpora lutea. Administration of VEGF Trap on Day 0 (n=3) and Day 5 (n=5) markedly inhibited thecal vascularisation and significantly reduced thecal cell proliferation. However, administration of VEGF Trap on follicular Day 5 did not inhibit preovulatory follicle expansion (>2000 KEY WORDS: angiogenesis, follicle, ovary |
m) and did not block ovulation of these follicles, with either preovulatory follicles or fresh points of ovulation evident in VEGF Trap treated ovaries. These results confirm that angiogenesis is vital for the development of dominant follicles. However, VEGF is not necessary for the expansion and ovulation of a dominant follicle from the time of follicle selection.