Angiogenic, mitogenic, and chemotactic activity of human follicular fluid

Human follicular fluid was found to induce the formation of new blood vessels on the chick chorioallantoic membrane 3 to 5 days after implantation. To characterize this response more fully, the effects of human follicular fluid on a continuous line of bovine aortic arch endothelial cells were studied. Human follicular fluid showed strong mitogenic activity toward endothelial cells, ranging from a threefold increase in thymidine incorporation at a dilution of 1:10 to a 1.4-fold increase at a dilution of 1:3200. Endothelial cells also exhibited a directional migration (chemotaxis) toward human follicular fluid. A 1:10 dilution of human follicular fluid induced a 6.8-fold increase in directional cellular migration through membranes with 8 microns pores, and a 1:800 dilution induced a 1.8-fold increase in migration. Endothelial cells responding to gradients of human follicular fluid also demonstrated a marked change in morphologic structure when compared with control cells. Human plasma and fibrinogen were angiogenic and chemotactic (but not mitogenic) toward endothelial cells, which suggested that fibrinogen may account for at least part of the angiogenic activity of human follicular fluid. These results indicate that human follicular fluid is strongly angiogenic and that this biologic activity can be associated with effects directly on endothelial cells in vitro.