| Project/Area Number |
11470350
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Tottori University School of Medicine |
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Principal Investigator |
TERAKAWA Naoki Tottori Univ.Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Souichi Tottori Univ.Dept.Obstet.Gynecol., Research Associates, 医学部・附属病院, 助手 (70304219)
IWABE Tomio Tottori Univ.Dept.Obstet.Gynecol., Research Associates, 医学部, 助手 (10284001)
HARADA Tasuku Tottori Univ.Dept.Obstet.Gynecol., Assistant Professor, 医学部, 講師 (40218649)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Endometriosis / Pathogenesis / Infertility / Endometriotic stromal cells / Peritoneal macrophages / Cytokines / IL-6 / IL-8 / 増殖・進展 / TNFα / 間質細胞 / TNF-α |
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| Research Abstract |
Endometriosis, which occurs in 10% of reproductive aged women, is characterized by the presence and growth of endometrial-like tissue outside the uterus. The pathogenesis of endometriosis and its link to infertility is controversial. Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNFα). The purpose of this study is to investigate whether IL-6, IL-8 and TNFα are related to progress and infertility of this disease.
Peritoneal fluid levels of IL-6, IL-8 and TNFα were significantly higher in patients with endometriosis compared with patients without endometriosis. The concentrations of these cytokines in patients with active endometriosis increased as the size and number of active lesions increased. Expressions of transcripts of IL-6 receptor, glycoprotein 130, IL-8 receptor and TNFα receptor were observed in both endometrial and endometrio
… More
tic stromal cells.
Tumor necrosis factor-α increased the expression of IL-6 messenger RNA and protein in endometriotic cells in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse 1-cell embryo to blastocyst in vitro. The percentage of motile spermatoza decreased by the addition of both IL-6 and soluble IL-6 receptor. These results suggested that IL-6 may relate to the infertility associated with endometriosis.
Interleukin-6 had no effect on the growth of stromal cells in endometrial tissue from the proliferative phase. In contrast, the addition of IL-6 induced significant inhibition of stromal cells in tissue from the secretary phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Interleukin-8 significantly increased the number of cells and DNA synthesis in the endometriotic stromal cells in a dose-dependent manner. Tumor necrosis factor-α induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNF α promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNF α were abolished by the adding anti-IL-8 antibody. These cytokines may associate with the progression of the disease.
In conclusion, IL-6, IL-8 and TNF α may contribute to the pathogenesis of endometriosis and infertility associated with endometriosis. Less
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