Suppression of luteal angiogenesis in the primate after neutralization of vascular endothelial growth factor

Manipulation of angiogenesis may have a profound effect on female reproduct ive function, but this has not yet been demonstrated by direct experiment i n species with ovulatory cycles similar to those in women. To investigate w hether angiogenesis could be inhibited in the primate corpus luteum, and th e consequences of such inhibition on luteal function, marmosets were treate d with an antibody to vascular endothelial growth factor (VEGF). Treatment commenced at the time of ovulation and was continued for 3 days (early lute al group) or 10 days (midluteal group). Bromodeoxyuridine was used to label proliferating cells, being administered 1 h before collecting ovaries from control and treated animals in the early or midluteal phase. Ovarian secti ons were stained using an antibody to bromodeoxyuridine, and a proliferatio n index was obtained; endothelial cell quantification was performed using f actor VIII as an endothelial cell marker. Intense proliferation in the earl y luteal phase was suppressed by anti-VEGF treatment. This resulted in bloc kade of development of the normally extensive capillary bed, as in the anim als treated until the mid-luteal phase the numbers of endothelial cells wer e reduced. The hormone-producing cells remained largely unaltered in the po sttreatment corpus luteum, although the presence of lipid accumulation, and small pockets of cells showing basophilia and nuclear condensation were ob served. Significantly, luteal function, as judged by secretion of progester one, was markedly compromised by the treatment, being reduced by 60% in com parison with controls. It is concluded that VEGF-mediated angiogenesis is a n essential component of luteal function in primates and therefore has the potential to be regulated.