Ovarian angiogenesis in rabbits: endotheliotrophic chemoattractant activity from isolated follicles and dispersed granulosa cells.

To test the hypothesis that angiogenesis is an important variable in ovarian folliculogenesis, we measured endothelial cell migration (chemotaxis) in media conditioned by rabbit ovarian cells. Endothelial cell migration, a reliable predictor of angiogenesis in vivo, was stimulated by media conditioned by isolated intact follicles (0.4-2.2 mm in diameter) from either unstimulated or hCG-stimulated (pseudopregnant) rabbits. In separate experiments, endothelial cell migration was also stimulated by granulosa cell-conditioned media. Follicular chemoattractant activity was associated with a molecular weight greater than 30,000 but was not correlated with follicular size or steroid concentrations in the media, although there was no evidence to suggest that the biological activity detected in media conditioned by either intact follicles or dispersed granulosa cells was the same. Demonstration of nonsteroidal chemoattractant activity in media conditioned by intact follicles or by dispersed granulosa cells provides evidence that follicles secrete a vascular chemotactic factor, and is consistent with a role for angiogenesis in follicle growth.