Furukawa Kazumi, Fujiwara Hiroshi, Sato Yukiyasu, Zeng Bin-Xiang, Fujii Haruko, Yoshioka Shinya, Nishi Eiichiro, Nishio Takeshi
Department of Gynecology and Obstetrics, Molecular Pathology Unit, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, and Department of Obstetrics and Gynecology, Osaka National Hospital, Japan.
Endocrinology. 2007 Jul;148(7):3056-64. doi: 10.1210/en.2006-1687. Epub 2007 Apr 19.
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.
人类黄体是一种独特的内分泌器官，它由排卵后的卵泡周期性构建而成。在人类黄体形成过程中，这一过程是组织重塑的典型病理生理模型，向心性血管发育的精确调控机制仍不清楚。最近有报道称血小板含有具有诱导内皮细胞迁移潜力的化学吸引物质。在本研究中，我们研究了血小板在人类黄体早期组织重塑过程中的作用。免疫组织化学研究表明，排卵后，大量红细胞和CD41阳性血小板定位于黄素化颗粒细胞之间的血管外部位。血小板沉积逐渐减少，并在微血管延伸的中央腔附近变得局限。在血管网络已经建立的黄体中期几乎观察不到血小板。这些血小板表达CD62P/P-选择素，并与细胞外基质共定位，表明血小板已被细胞外基质激活。在4天的培养过程中，与血小板直接接触可显著促进从接受体外受精治疗的患者中分离出的黄素化颗粒细胞产生孕酮。血小板衍生的可溶性因子诱导颗粒细胞形态铺展。这些因子还增加了人脐静脉内皮细胞的迁移，而黄素化颗粒细胞则减弱了血小板诱导的内皮细胞迁移。这些发现使我们提出了一个新的概念，即血小板是人类黄体重塑过程中内皮细胞迁移和颗粒细胞黄素化的调节因子。
