Platelets are novel regulators of neovascularization and luteinization during human corpus luteum formation
Platelets are novel regulators of neovascularization and luteinization during human corpus luteum formation
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DOI：
10.1210/en.2006-1687
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Nishio, Takeshi
中科院分区：
文献类型：
--
作者：
Furukawa, Kazumi;Fujiwara, Hiroshi;Nishio, Takeshi
人的黄体是一种独特的内分泌器官，由排卵的卵泡周期性地构建而成。黄体形成是众所周知的组织重塑的病理生理学模型，在黄体形成过程中，调节向心性血管发育的确切机制尚不清楚。最近，据报道，血小板中含有可能诱导内皮细胞迁移的化学吸引物质。在这项研究中，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，排卵后相当数量的红细胞和CD41阳性的血小板定位于黄体颗粒细胞之间的血管外部位。血小板沉积逐渐减少，并在微血管向其延伸的中央腔附近变得有限。在黄体中期，当血管网络已经建立时，几乎没有观察到血小板。这些血小板表达CD62P/P-选择素，并与细胞外基质共定位，提示血小板已被细胞外基质激活。从体外受精治疗患者分离的黄体化颗粒细胞在4d培养过程中与血小板直接接触可显著促进孕酮的产生。血小板衍生的可溶性因子引起颗粒细胞形态的扩散。这些因素也增加了人脐静脉内皮细胞的迁移，而黄体化的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，即在人类黄体重塑过程中，血小板是内皮细胞迁移和颗粒细胞黄体化的调节者。
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.