Platelets Are Novel Regulators of Neovascularization and Luteinization during Human Corpus Luteum Formation

Abstract

The human corpus luteum is a unique endocrine organ that is periodically constructed from the ovulated follicle. During human corpus luteum formation, which is well known as a pathophysiological model for tissue remodeling, the precise mechanisms by which centripetal vascular development is regulated remain unknown. Recently platelets were reported to contain chemoattractive substances with the potential to induce endothelial migration. In this study, we examined the involvement of platelets in the early tissue remodeling process of the human corpus luteum. An immunohistochemical study demonstrated that considerable amounts of red blood cells and CD41-positive platelets were localized at extravascular sites among luteinizing granulosa cells after ovulation. Platelet deposition gradually decreased and became limited near the central cavity toward which microvessels were extending. Platelets were hardly observed in the midluteal phase when the vascular network had already been established. These platelets expressed CD62P/P-selectin and were colocalized with extracellular matrix, suggesting that platelets had been activated by the extracellular matrix. Progesterone production by luteinizing granulosa cells that were isolated from patients undergoing in vitro fertilization therapy was significantly promoted by direct contact with platelets during 4-d culture. Platelet-derived soluble factors induced spreading in granulosa cell morphology. These factors also increased the migration of human umbilical vein endothelial cells, whereas luteinizing granulosa cells attenuated platelet-induced endothelial cell migration. These findings lead us to propose the novel concept that platelets are regulators of endothelial cell migration and granulosa cell luteinization in the remodeling process of the human corpus luteum.