The long-term goals of the proposed studies are to elucidate the mechanisms that control new blood vessel growth - a process called angiogenesis - in the follicle and corpus luteum. In the ovary, blood vessels undergo repeated and rapid growth and involution in conjunction with follicular growth and corpus luteum formation and regression. We believe that vessel growth is controlled by the release of an angiogenic factor from the granulosa cells of the developing follicle and from the corpus luteum - a mechanism analogous to that by which tumors recruit a blood supply. In preliminary studies, we have shown that pieces of ovary from immature rats primed with PMSG and containing follicles or new corpora lutea are consistently and rapidly revascularized when placed on the chorioallantoic membrane (CAM) of the chicken embryo, a commonly used assay for angiogenic activity. Unstimulated ovaries and regressing corpora lutea have a much weaker effect on the CAM. Other rat tissues such as liver, adrenal, skeletal muscle, and spleen have no effect. To confirm and expand these observations we propose to carry out experiments with three specific aims: 1) we will expand our preliminary observations on the vascular changes induced by rat follicle-containing ovarian tissue and rat corpora lutea on the CAM and determine whether isolated granulosa cells are angiogenic on the CAM; 2) we will determine if material active in angiogenesis assays can be extracted from rat ovarian tissues and bovine corpora lutea; 3) we will attempt to purify and characterize the ovarian angiogenic factor(s). Identification of the putative ovarian angiogenic factor and an understanding of how its production is controlled could lead to a better understanding of normal and abnormal ovarian function.
