Analysis of the system to maintain the local circulation of tissue fluid throughout human fresh corpus luterum during corpus luteum formation

人的黄体是由排卵卵泡周期性发育而成的独特的内分泌器官。在人类黄体形成过程中，这是众所周知的组织重塑的病理生理学模型，向心性血管发育调节的精确机制仍然未知。最近，据报道血小板含有具有诱导内皮细胞迁移潜力的化学吸引物质。在这个项目中，我们显示了血小板在人类黄体的早期组织重塑过程中的参与，以及血小板被细胞外基质激活。在培养过程中直接接触血小板可显著促进黄体化颗粒细胞的孕酮生成。血小板源性可溶性因子诱导颗粒细胞形态的扩展。这些因素也增加了人脐静脉内皮细胞的迁移，而黄体化颗粒细胞衰减血小板诱导的内皮细胞迁移。这些发现使我们提出了新的概念，即血小板是调节内皮细胞迁移和颗粒细胞黄体化在人类黄体重塑过程中。该项目提供了进一步的证据，证明血小板是凝血系统的主要贡献者，在成人卵巢组织重塑过程中诱导细胞分化和迁移。这些发现也支持了最近的概念，即血小板在伤口愈合过程中起着重要作用，并将有助于阐明炎症性病变中的血管外循环机制，以及开发用于不明原因不孕症和习惯性流产的新疗法。

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 remains unknown. Recently, platelets were reported to contain chemoattractive substances with the potential to induce endothelial migration. In this project, we showed the involvement of platelets in the early tissue remodeling process of the human corpus luteum and the activation of platelets by the extracellular matrix. Progesterone production by luteinizing granulosa cells was significantly promoted by direct contact with platelets during 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. This project provides further evidence that platelets, which are the main contributors to the coagulation system, induce cell differentiation and migration in the tissue remodeling process in the adult human ovary. These findings also support the recent concept that platelets play an important role in wound healing processes and will contribute to clarifying the mechanism of extravascular circulation in inflammatory lesions and to development of the novel therapy for unexplained infertility and habitual abortion.