EXPRESSION OF THE ANGIOGENIC FACTORS, BASIC FIBROBLAST GROWTH-FACTOR AND VASCULAR ENDOTHELIAL GROWTH-FACTOR, IN THE OVARY

In adult tissues, vascular growth (angiogenesis) occurs normally durin g tissue repair, such as in the healing of wounds and fractures. Inapp ropriate vascular growth is associated with various pathological condi tions. These conditions include tumor growth, retinopathies, hemangiom as, fibroses, and rheumatoid arthritis in the case of rampant vascular growth and nonhealing wounds and fractures in the case of inadequate vascular growth. The female reproductive organs exhibit dramatic, peri odic growth and regression, accompanied by equally dramatic changes in their rates of blood flow. Thus, it is not surprising that they are s ome of the few adult tissues in which angiogenesis occurs as a normal process. Ovarian follicles and corpora lutea contain and produce angio genic factors. These angiogenic factors bind heparin and seem to belon g to the fibroblast growth factor (FGF) and vascular endothelial growt h factor (VEGF) families of proteins. Based on our studies of the patt ern of expression of FGF and its major receptors in bovine, ovine, and porcine corpora lutea, we have suggested that FGF may influence not o nly luteal cell proliferation but also cell death, thereby regulating cell turnover in the luteal vascular and nonvascular compartments. In addition, we recently have shown that luteal expression of VEGF is gre atest during the early luteal phase, coincident with luteal vasculariz ation. Moreover, VEGF is present exclusively in luteal connective tiss ue and perivascular (arteriolar smooth muscle and capillary pericyte) cells. In fact, the first thecal-derived cells to invade the granulosa -derived regions immediately after ovulation seem to be VEGF-containin g pericytes. We have therefore hypothesized that ovarian pericytes pla y a key role in vascularization of developing follicles and corpora lu tea. Further understanding of the specific physiological roles of thes e factors in follicular and luteal growth, development, and function w ill ultimately lead to improved methods of regulating fertility.