Vascular morphogenesis in the primate ovary.

Ovarian function is dependent on intense cyclical vascular morphogenesis and regression. The molecular and cellular pathways involved in the generation of new capillary networks in the ovary are now being elucidated. Focussing on the marmoset, the course of angiogenesis at different stages of follicular maturation and in the corpus luteum throughout the cycle and in early pregnancy have been quantified and major progress has been made in the evaluation of the role of vascular endothelial growth factor (VEGF). To study the physiological role of VEGF in follicular and luteal angiogenesis in detail, VEGF was inhibited during defined stages of the cycle in vivo. VEGF antagonist administered throughout the follicular phase of the cycle resulted in a marked decrease in endothelial cell proliferation in developing antral follicles, accompanied by a decline in granulosa cell proliferation, restriction of follicular growth and inhibition of ovulation. An outstanding feature in the ovary is the intense angiogenesis that occurs during the early luteal phase. VEGF inhibitors markedly suppressed this angiogenesis, resulting in a marked restriction in the development of the microvascular tree and suppression of plasma progesterone. These studies showed that VEGF is essential for normal follicular and luteal angiogenesis and function, and demonstrated how luteal angiogenesis in particular could serve as a sensitive bioassay for putative angiogenic antagonists. Antagonists of VEGF are potent tools for investigating the role of angiogenic factors within the ovary and may have applications to the treatment of reproductive disorders characterised by alterations in normal vascular structure or function.