Expression of the angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, in the...

In adult tissues, vascular growth (angiogenesis) occurs normally during tissue repair, such as in the healing of wounds and fractures. Inappropriate vascular growth is associated with various pathological conditions. These conditions include tumor growth, retinopathies, hemangiomas, 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, periodic growth and regression, accompanied by equally dramatic changes in their rates of blood flow. Thus, it is not surprising that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Ovarian follicles and corpora lutea contain and produce angiogenic factors. These angiogenic factors bind heparin and seem to belong to the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) families of proteins. Based on our studies of the pattern of expression of FGF and its major receptors in bovine, ovine, and porcine corpora lutea, we have suggested that FGF may influence not only 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 greatest during the early luteal phase, coincident with luteal vascularization. Moreover, VEGF is present exclusively in luteal connective tissue 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-containing pericytes. We have therefore hypothesized that ovarian pericytes play a key role in vascularization of developing follicles and corpora lutea. Further understanding of the specific physiological roles of these factors in follicular and luteal growth, development, and function will ultimately lead to improved methods of regulating fertility.