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

Department of Gynecology and Obstetrics, Kyoto University, Kioto, Kyōto, Japan
Endocrinology (Impact Factor: 4.5). 08/2007; 148(7):3056-64. DOI: 10.1210/en.2006-1687
Source: PubMed


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.

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Available from: Eiichiro Nishi
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    • "Moreover, the blood clot formed during ovulation might stimulate cell migration. Indeed, platelets are a better stimulant for endothelial cells migration than granulosa cells themselves [19]. Examples of proangiogenic cytokines acting on this stage of the cycle include the cytokines fibroblast growth factor 2 (FGF2), VEGF, platelet-derived growth factor (PDGF) family, and angiopoietin (Ang). "
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    ABSTRACT: In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced cytokines, such as tumor necrosis factor α (TNF), interferon gamma (IFNG), or Fas ligand (FASL), pointed out their role on angiogenic activity modulation throughout the luteal phase. Thus, the main purpose of this review is to highlight the interaction between immune, endothelial, and luteal steroidogenic cells, regarding vascular dynamics/changes during establishment and regression of the equine CL.
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    • "Stimulation of granulosa cells by hCG as well as by IGFs and hypoxia induced up-regulation of VEGF (Hazzard et al., 1999; Tropea et al., 2006; Taylor et al., 2007) that is cardinal for generation of healthy ovulatory follicles and CL (Distler et al., 2003). In addition to VEGF, other factors such as angiopoietin (1 and 2; (Sugino et al., 2005), leukocytes (Polec et al., 2011) and platelets (Furukawa et al., 2007; Nurden, 2007) contribute to the remodeling of endothelial cells and luteinized granulosa cells in the process of CL formation. In the current study we found that PEDF regulation is hormonally affected inversely to VEGF, further implying a role for PEDF as a negative regulator of ovarian angiogenesis. "
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    • "Indeed, peripheral blood lymphocytes and macrophages indicated a luteotrophic effect as these cells stimulated P secretion upon co-culture with granulosa cells [42-44]. Meanwhile, Furukawa et al. revealed that platelets are novel regulators of neovascularization and luteinization during the early luteal phase in humans [45]. An increased number of platelets localized to extravascular sites among luteinizing granulosa cells after ovulation and gradually decreased toward the mid luteal phase [45], that are similar to the PMN profile observed in the present study. "
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