The effect of stress on immune system and the progression of endometriosis.

• Project/Area Number: 26462479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: University of Toyama
• Principal Investigator: YOSHINO OSAMU 富山大学, 大学院医学薬学研究部(医学), 准教授 (00466757)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮内膜症 / ストレス / 交感神経 / 副交感神経 / 炎症 / 自律神経

Outline of Final Research Achievements

Endometriosis is known as an inflammatory disease, and macrophages are involved in inflammation. Using human peritoneal macrophages, activation of nicotinic acethylcholine receptor (nAchR) led to suppress of inflammatory cytokines in macrophages in vitro. A mouse endometriosis model exhibited the effect of activation of nAchR on suppression of endometriotic lesions.
As Ach is known to be a transmitter of parasympathetic nerves, we hypothesized that in endometriosis patients, sympathetic nerves could be activated compared to parasympathetic nerves. We evaluated the condition of sympathetic/parasympathetic nerves in patients, and found the trend that serum concentration of noradrenaline, and the trait anxiety is higher in endometriosis patients rather than in non-endometriosis patients.

Research Products

• [Journal Article] PAI-1 in granulosa cells is suppressed directly by statin and indirectly by suppressing TGF-β and TNF-α in mononuclear cells by insulin-sensitizing drugs. (2017)
  • Author(s): Yamada-Nomoto K, Yoshino O, Akiyama I, Iwase A, Ono Y, Nakamura T, Harada M, Nakashima A, Shima T, Ushijima A, Osuga Y, Chang RJ, Shimasaki S, Saito S.
  • Journal Title: Am J Reprod Immunol. Volume: 78 Issue: 1 Pages: 1-8
  • DOI: 10.1111/aji.12669
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oral contraceptive therapy reduces serum relaxin-2 in elite female athletes. (2017)
  • Author(s): Nose-Ogura S, Yoshino O, Yamada-Nomoto K, Nakamura M, Harada M, Dohi M, Okuwaki T, Osuga Y, Kawahara T, Saito S.
  • Journal Title: J Obstet Gynaecol Res. Volume: 43 Issue: 3 Pages: 530-5
  • DOI: 10.1111/jog.13226
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women. (2017)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Azhary JM, Yoshino O, Izumi G, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Endocrinology Volume: 158 Pages: 84-97
  • DOI: 10.1210/en.2016-1511
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alpha-7 nicotinic acetylcholine receptor (nAChR) agonist inhibits the development of endometriosis by regulating inflammation. (2016)
  • Author(s): Yamada-Nomoto K, Yoshino O, Akiyama I, Ushijima A, Ono Y, Shima T, Nakashima A, Hayashi S, Kadowaki M, Osuga Y, Saito S.
  • Journal Title: Am J Reprod Immunol. Volume: 76 Issue: 6 Pages: 491-498
  • DOI: 10.1111/aji.12592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The assessment of myometrium perfusion in patients with uterine fibroid by arterial spin labeling MRI. (2016)
  • Author(s): Takahashi N, Yoshino O, Hiraike O, Maeda E, Nakamura M, Hori M, Harada M, Koga K, Saito S, Fujii T, Osuga Y.
  • Journal Title: Springerplus. Volume: 5 Pages: 1907-1907
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Usefulness of T2 star-weighted imaging in ovarian cysts and tumors. (2016)
  • Author(s): Takahashi N, Yoshino O, Maeda E, Naganawa S, Harada M, Koga K, Hiraike O, Nakamura M, Tabuchi T, Hori M, Saito S, Fujii T, Osuga Y.
  • Journal Title: J Obstet Gynaecol Res Volume: 42 Issue: 10 Pages: 1336-1342
  • DOI: 10.1111/jog.13056
  • Peer Reviewed
• [Journal Article] A new era in reproductive medicine: consequences of third-party oocyte donation for maternal and fetal health. (2016)
  • Author(s): Saito S, Nakabayashi Y, Nakashima A, Shima T, Yoshino O.
  • Journal Title: Semin Immunopathol. Volume: 38 Pages: 687-697
  • Peer Reviewed
• [Journal Article] A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome. (2016)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Mol Cell Endocrinol Volume: 428 Pages: 161-169
  • DOI: 10.1016/j.mce.2016.03.032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Paternal Antigen-Specific Treg Cells in Successful Implantation. (2016)
  • Author(s): Saito S, Shima T, Nakashima A, Inada K, Yoshino O.
  • Journal Title: Am J Reprod Immunol. Volume: 75 Issue: 3 Pages: 310-316
  • DOI: 10.1111/aji.12469
  • Peer Reviewed
• [Journal Article] Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation. (2015)
  • Author(s): Harada, M., Nose, E., Takahashi, N., Hirota, Y., Hirata, T., Yoshino, O., Koga, K., Fujii, T., Osuga, Y
  • Journal Title: Gynecological Endocrinology Volume: 31 Issue: 10 Pages: 783-787
  • DOI: 10.3109/09513590.2015.1062862
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Paternal antigen-specific proliferating regulatory T cells are increased in uterine-draining lymph nodes just before implantation and in pregnant uterus just after implantation by seminal plasma-priming in allogeneic mouse pregnancy. (2015)
  • Author(s): Shima T, Inada K, Nakashima A, Ushijima A, Ito M, Yoshino O, Saito S.
  • Journal Title: J Reprod Immunol. Volume: 108 Pages: 78-82
  • DOI: 10.1016/j.jri.2015.02.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 子宮内膜症治療の未来図 手術と薬物療法のコンビネーション (2014)
  • Author(s): 吉野 修、高村 将司、甲賀かをり、大須賀 穣、齋藤 滋
  • Journal Title: 臨床婦人科産科 Volume: 68 Pages: 1183-1187
• [Journal Article] 子宮因子による不妊 (2014)
  • Author(s): 吉野 修、齋藤 滋
  • Journal Title: 産婦人科の実際 Volume: 63 Pages: 1535-1539
• [Journal Article] 特集ＣＴ、ＭＲＩ戦略的 活用ガイド (2014)
  • Author(s): 吉野 修、齋藤 滋
  • Journal Title: medicina Volume: 51 Pages: 336-7
• [Journal Article] 不妊症と子宮筋腫 (2014)
  • Author(s): 吉野 修、齋藤 滋
  • Journal Title: 産婦人科の実際 Volume: 63 Pages: 1387-1391
• [Journal Article] 治療を見据えた子宮筋腫の画像評価 (2014)
  • Author(s): 吉野 修、齋藤 滋
  • Journal Title: 臨床婦人科産科 Volume: 68 Pages: 202-208
• [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] A first case report of torsion of the substituted small intestine 39 years after vaginoplasty using ileum segment. (2014)
  • Author(s): Yosuke Ono, Osamu Yoshino, Masami Ito, Sho Soeda, Tomoko Shima and Shigeru Saito
  • Journal Title: Med J Obstet Gyneco Volume: 2 Pages: 1041-1041
  • Peer Reviewed
• [Journal Article] Serum concntration of bone morphogenetic proteins (BMPs) is not linked to serum anti-mullerian hormomne (AMH) level. (2014)
  • Author(s): Sayaka Ogura-Nose, Osamu Yoshino, Ikumi Akiyama, Yasushi Hirota, Tetsuya Hirata,Miyuki Harada, Hisahiko Hiroi, KaoriKoga, Shigeru Saito, Yutaka Osuga, Tomoyuki Fujii
  • Journal Title: Integrative Molecular Medicine Volume: 1 Pages: 26-8
  • Peer Reviewed
• [Journal Article] Application of detergents or high hydrostatic pressure as decellularization process in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models (2014)
  • Author(s): E.G.Santoso, K.Yoshida, Y.Hirota, M.Aizawa,O.Yoshino, A.Kishida, Y.Osuga, S.Saito, T.Ushida, K.S.Furukawa,
  • Journal Title: PLoS ONE Volume: 9 Issue: 7 Pages: 1-13
  • DOI: 10.1371/journal.pone.0103201
  • Peer Reviewed / Open Access
• [Presentation] 子宮内膜症病巣におけるS1Pシステムとその作用についての検討 (2016)
  • Author(s): 吉野 修、野本かおり、小野洋輔、中島彰俊、島友子、可野邦行、青木淳賢、齋藤滋
  • Organizer: 日本生殖免疫学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-12-02
• [Presentation] 1.PAI-1 in granulosa cells is suppressed directly by statin and indirectly by suppressing TGF-β and TNF-α in mononuclear cells by insulin sensitizing drugs. (2016)
  • Author(s): Osamu Yoshino, Kaori Yamada-Nomoto, Ikumi Akiyama, Akira Iwase, Akitoshi Nakashima, Tomoko Shima, Yutaka Osuga and Shigeru Saito
  • Organizer: 日本産婦人科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-22
• [Presentation] T2 star 強調MRI画像(T2*)の卵巣病変診断における有用性 (2016)
  • Author(s): 吉野 修、高橋 望、前田 恵理子、大須賀 穣、藤井 知行、齋藤 滋
  • Organizer: 北陸生殖医学会
  • Place of Presentation: 金沢
• [Presentation] 子宮内膜症病巣におけるブラジキニン受容体の発現と作用に関する検討 (2015)
  • Author(s): 吉野 修、野本かおり、小野洋輔、長谷川 亜希子、大須賀 穣、齋藤 滋
  • Organizer: 第30回日本生殖免疫学会総会・学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2015-11-21
• [Presentation] 多嚢性卵巣症候群(PCOS)に関与する因子plasminogen activator inhibitor-1 (PAI-1)の制御に関する検討。 (2015)
  • Author(s): 吉野 修、岩瀬 明、秋山 育美、島 友子、大須賀 穣、齋藤 滋1
  • Organizer: 第６７回日本産婦人科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-09
• [Presentation] 基礎的見地から卵巣生理・病理学における顆粒膜細胞と周辺細胞との関連についての検討 (2014)
  • Author(s): 吉野 修
  • Organizer: 第29回日本生殖免疫学会総会・学術集会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-12 – 2014-12-13
  • Invited
• [Presentation] ４０歳以上の初回IVF-ET症例における血中anti-Müllerian hormone (AMH)の意義に関する検討。 (2014)
  • Author(s): 吉野 修、能瀬 さやか、副田 翔、西井 修、河村 寿宏、齋藤 滋
  • Organizer: 第62回北日本産科婦人科学会 総会・学術講演会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-27 – 2014-09-28
• [Presentation] 顆粒膜細胞から産生されるGrowth differentiation factor (GDF)-3 はbone morphogenetic protein (BMP)サイトカインにより誘導され、BMPによるＬＨ受容体発現低下をキャンセルする。 (2014)
  • Author(s): 1.吉野 修、秋山 育美、大須賀 穣、甲賀かをり、原田 美由紀、齋藤 滋、藤井 知行
  • Organizer: 第66回日本産婦人科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20