The effect of human follicular fluid on endothelial cells: proliferation and DNA synthesis

Human follicular fluid has been reported to cause angiogenesis. Although endothelial cell mitogenesis is a major component of the process of angiogenesis, the findings in the literature regarding the effects of human follicular fluid in in vitro endothelial cell growth assays are equivocal. In the present study, we examined the effect of human follicular fluid from preovulatory follicles on fetal bovine aortic endothelial cell proliferation. Human serum was used as a control since follicular fluid is largely a transudate of serum and could contain serum-derived endothelial cell mitogens. Neither human follicular fluid nor serum directly caused endothelial cell proliferation. However, follicular fluid, as well as serum, caused an increase in thymidine incorporation by endothelial cells, and resulted in an increased proportion of cells in the DNA synthesis and G2 phases of the cell cycle. Although follicular fluid was not directly mitogenic, it, in contrast to human serum, together with fetal bovine serum markedly enhanced endothelial cell proliferation beyond that caused by fetal bovine serum alone. These results suggest that a combination of factors, some of ovarian origin present in follicular fluid, and others from as yet unidentified sources, govern the mitogenic component of new blood vessel growth in the ovary.