The role of phagocytes in the pathogenesis of endometriosis

• Project/Area Number: 26462478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: KOGA KAORI 東京大学, 医学部附属病院, 准教授 (10396723)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮内膜症 / マクロファージ / 樹状細胞

Outline of Final Research Achievements

We found that the proportion of mannose receptor (MR) positive - myeloid DC type 1 was higher in endometriosis samples than in controls. The blocking of MR reduced phagocytosis of dESC by Mo-DC. Mo-DC cultured with dESC expressed higher levels of interleukin (IL)-1β and IL-6 than controls.

According to these findings, we suggested that oeritoneal DC in endometriosis tissue express high levels of MR, which promotes phagocytosis of dead endometrial cells, and thereby contributes to the etiology of endometriosis.

Research Products

• [Journal Article] Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells. (2017)
  • Author(s): Makabe T, Koga K, Miyashita M, Takeuchi A, Sue F, Taguchi A, Urata Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Reprod Immunol Volume: 119 Pages: 44-48
  • DOI: 10.1016/j.jri.2016.12.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis. (2016)
  • Author(s): Takeuchi A, Koga K, Miyashita M, Makabe T, Sue F, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 207 Pages: 157-161
  • DOI: 10.1016/j.ejogrb.2016.10.053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis. (2016)
  • Author(s): Izumi G, Koga K, Takamura M, Makabe T, Nagai M, Urata Y, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 107 Issue: 1 Pages: 167-173
  • DOI: 10.1016/j.fertnstert.2016.09.036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of ovarian cancer after excision of endometrioma. (2016)
  • Author(s): Haraguchi H, Koga K, Takamura M, Makabe T, Sue F, Miyashita M, Urata Y, Izumi G, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Oda K, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 106 Issue: 6 Pages: 1432-1437
  • DOI: 10.1016/j.fertnstert.2016.07.1077
  • Peer Reviewed
• [Journal Article] Neutrophil depletion reduces endometriotic lesion formation in mice. (2016)
  • Author(s): Takamura M, Koga K, Izumi G, Urata Y, Nagai M, Hasegawa A, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol Volume: 76 Issue: 3 Pages: 193-198
  • DOI: 10.1111/aji.12540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of 1,25-dihydroxy vitamin D3 on endometriosis. (2016)
  • Author(s): Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Clin Endocrinol Metab Volume: 101 Issue: 6 Pages: 2371-2379
  • DOI: 10.1210/jc.2016-1515
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells. (2016)
  • Author(s): Taguchi, A., Koga, K., Kawana, K., Makabe, T., Sue, F., Miyashita, M., Yoshida, M., Urata, Y., Izumi, G., Takamura, M., Harada, M., Hirata, T., Hirota, Y., Wada-Hiraike, O., Fujii, T., Osuga, Y
  • Journal Title: American Journal of Reproductive Immunology Volume: 75 Issue: 4 Pages: 486-492
  • DOI: 10.1111/aji.12489
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of 1,25-dihydroxy vitamin D3 on endometriosis (2016)
  • Author(s): Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y
  • Journal Title: J Clin Endocrinol Metab Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Simultaneous Detection and Evaluation of Four Subsets of CD4+ T Lymphocyte in Lesions and Peripheral Blood in Endometriosis. (2015)
  • Author(s): Takamura, M., Koga, K., Izumi, G., Hirata, T., Harada, M., Hirota, Y., Hiraike, O., Fujii, T., Osuga, Y
  • Journal Title: American Journal of Reproductive Immunology Volume: 74 Issue: 6 Pages: 480-486
  • DOI: 10.1111/aji.12426
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis (2015)
  • Author(s): Koga K, Takamura M, Fujii T, Osuga Y
  • Journal Title: Fertil Steril Volume: 1104 Issue: 4 Pages: 793-801
  • DOI: 10.1016/j.fertnstert.2015.08.026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Viperin is induced following toll-like receptor 3 (TLR3) ligation and has a virus-responsive function in human trophoblast cells (2015)
  • Author(s): Wang B, Fang Y, Wu Y, Koga K, Osuga Y, Lv S, Chen D, Zhu Y, Wang J, Huang H
  • Journal Title: Placenta Volume: in press Issue: 6 Pages: 667-673
  • DOI: 10.1016/j.placenta.2015.03.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Laparoscopic excision of ovarian endometrioma does not exert a qualitative effect on ovarian function: insights from in vitro fertilization and single embryo transfer cycles (2015)
  • Author(s): Harada M, Takahashi N, Hirata T, Koga K, Fujii T, Osuga Y
  • Journal Title: J Assist Reprod Genet Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclic Stretch Augments Production of Neutrophil Chemokines, Matrix Metalloproteinases, and Activin A in Human Endometrial Stromal Cells. (2015)
  • Author(s): Izumi G, Koga K, Takamura M, Osuga Y.
  • Journal Title: Am J Reprod Immunol Volume: epub Issue: 6 Pages: 501-506
  • DOI: 10.1111/aji.12359
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-1β increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells. (2014)
  • Author(s): Urata Y, Koga K, Hirota Y, Akiyama I, Izumi G, Takamura M, Nagai M, Harada M, Hirata T, Yoshino O, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol. Volume: 72 Issue: 5 Pages: 496-503
  • DOI: 10.1111/aji.12282
  • Peer Reviewed / Open Access
• [Journal Article] Dienogest reduces proliferation, aromatase expression and angiogenesis, and increases apoptosis in human endometriosis. (2014)
  • Author(s): Miyashita M, Koga K, Takamura M, Izumi G, Nagai M, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Gynecol Endocrinol. Volume: 30 Issue: 9 Pages: 644-648
  • DOI: 10.3109/09513590.2014.911279
  • Peer Reviewed / Open Access
• [Presentation] The recurrence of endometrioma after conservative surgeries: prevalence, impact on QOL, and prevention (2016)
  • Author(s): Kaori Koga
  • Organizer: Asian Conference on Endometriosis
  • Place of Presentation: Osaka
  • Year and Date: 2016-09-22
  • Int'l Joint Research / Invited
• [Presentation] 子宮内膜症合併不妊の取り扱い 不妊クリニックと手術施設の連携を目指して (2016)
  • Author(s): 甲賀かをり
  • Organizer: 第34回日本受精着床学会総会・学術講演会
  • Place of Presentation: 長野
  • Year and Date: 2016-09-15
• [Presentation] Recurrence of Endometrioma after Conservative Surgery: (2016)
  • Author(s): Kaori Koga
  • Organizer: Taiwan Endometriosis Society 2016
  • Place of Presentation: Taipei
  • Year and Date: 2016-07-24
  • Int'l Joint Research