Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is essential for the angiogenesis required for the formation of the corpus luteum; however, its role in ongo ing luteal angiogenesis and in the maintenance of the established vascular network is unknown. The aim of this study was to determine whether VEGF inh ibition could intervene in ongoing luteal angiogenesis using immunoneutrali sation of VEGF starting in the mid-luteal phase. In addition, the effects o n endothelial cell survival and the recruitment of periendothelial support cells were examined. Treatment with a monoclonal antibody to VEGF, or mouse gamma globulin for control animals, commenced on day 7 after ovulation and continued for 3 days. Bromodeoxyuridine (BrdU), used to label proliferatin g cells to obtain a proliferation index, was administered one hour before c ollecting ovaries from control and treated animals. Ovarian sections were s tained using antibodies to BrdU, the endothelial cell marker, CD31, the per icyte marker, alpha-smooth muscle actin, and 3 ' end DNA fragments as a mar ker for apoptosis. VEGF immunoneutralisation significantly suppressed endot helial cell proliferation and the area occupied by endothelial cells while increasing pericyte coverage and the incidence of endothelial cell apoptosi s. Luteal function was markedly compromised by anti-VEGF treatment as judge d by a 50% reduction in plasma progesterone concentration. It is concluded that ongoing angiogenesis in the mid-luteal phase is primarily driven by VE GF, and that a proportion of endothelial cells of the mid-luteal phase vasc ulature are dependent on VEGF support.