Angiogenesis in the primate ovary.

The ovary is distinctive in undergoing cyclic changes in angiogenesis that play a critical role in the normal functioning of the female reproductive system. The current paper describes the use of the marmoset monkey as an in vivo model in which the cellular and molecular regulation of angiogenesis in the ovary can be investigated and the effects of manipulation of angiogenic factors elucidated. The studies are based on quantifying changes in blood vessel area and endothelial cell proliferation, monitoring changes in expression patterns of putative angiogenic regulatory factors and targeting these factors by antagonists in vivo. Quantification of endothelial cell proliferation shows that angiogenesis commences in the pre-antral follicle, increases with follicular development and becomes intense in the early corpus luteum. Vascular endothelial growth factor (VEGF), a principal angiogenic factor, is synthesized by the developing follicle and corpus luteum. Administration of specific antagonists in vivo for selected periods of the ovulatory cycle shows that inhibition of VEGF results in a marked decrease in endothelial cell proliferation in the follicle and is accompanied by a decline in granulosa cell proliferation. Inhibition during the early or mid-luteal phase results in a marked suppression in luteal angiogenesis, failure of development of the microvascular tree and suppression of luteal function. Manipulation of angiogenesis should be a novel approach to either promoting or inhibiting the normal processes of folliculogenesis, ovulation and corpus luteum function.