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: 4.64). 08/2007; 148(7):3056-64. DOI: 10.1210/en.2006-1687
Source: PubMed

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.

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    ABSTRACT: Corpus luteum (CL) is a small, transient endocrine gland formed following ovulation from the secretory cells of the ovarian follicles. The main secretory product of CL is progesterone, which is required for the establishment and maintenance of pregnancy and regulates various reproductive functions. Progesterone plays a key role in the regulation of the length of estrous cycle and in the implantation of the blastocysts. Additionally, progesterone serves as a negative feedback mechanism to the hypothalamus to suppress further follicular development. The inadequate progesterone production is the major cause of infertility and embryonic loss, since progesterone is essential for both endometrial growth and embryo survival. Corpus luteum is formed following ovulation, but the real stimulus for luteinization represents the preovulatory LH surge from hypophysis. Even in case when ovulation does not occur, granulosa cells will differentiate and form CL, while oocyte will be trapped within the non- Correspondence should be addressed to Kaveh Mohammadi Khanghah,; Tel: +98-9189846319. Journal of Biology and today's world 2013, volume 2, issue 3, pages: 153-172 154 | P a g e ovulating structure. The major biologic mechanisms involved in CL development, function, and regression will be discussed in this review.
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    ABSTRACT: To explore differences in follicle transcriptomes in patients having oocyte maturation with either a bolus of hCG or GnRHa. Cumulus cells (CC) and mural granulosa cells (MGC) were isolated from preovulatory follicles in patients undergoing controlled ovarian stimulation, prospectively randomized to GnRHa or hCG triggering. University-based facilities for clinical services and research. Twenty women with indication for IVF or intracytoplasmic sperm injection treatment were randomly allocated to hCG or GnRH agonist (GnRHa) trigger. MGC and CC were collected from individual follicles in connection with oocyte retrieval. RNA was extracted, labeled, amplified, and hybridized on HumanGene1.0ST GeneChip Affymetrix array. Expression data were robust multichip average normalized and compared using Partek and Ingenuity software. Array data were confirmed with reverse transcription-polymerase chain reaction analysis. Comparing the transcriptomes between the groups, 391 and 252 genes were differentially expressed (fold change >1.5) in CC and MGC, respectively. The enriched bionetworks showed that CC genes highly represented "lipid metabolism and small molecule biochemistry" (network score, 41), while in MGC, the top network was "cardiovascular development and function and cellular movement" (network score, 50). For both CC and MGC, the regulator analysis suggested LH as the upstream regulator for the difference observed. In CC, the LH receptor was more highly expressed after GnRHa trigger, while in MGC, genes involved in angiogenesis such as angiopoietin 1 and semaphorin 3A were down- and up-regulated, respectively, in GnRHa- as compared with hCG-triggered patients. The comparisons between somatic cell transcriptomes from GnRHa- and hCG-triggered follicles showed significant functional differences in both CC (steroidogenesis) and MGC (angiogenesis) compartments.
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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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