Study of antimicrobial peptides and bacterial endotoxin in endometriosis

• Project/Area Number: 24592474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagasaki University
• Principal Investigator: KHAN Khaleque 長崎大学, 医歯薬学総合研究科 (医学系), 助教 (60336162)
• Co-Investigator(Kenkyū-buntansha): KITAJIMA Michio 長崎大学, 病院(医学系), 講師 (50380845)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: endometriosis / inflammation / bacterial contamination / TLR4 / human beta-defensin / SLPI / infection / defensin / Human beta-defensin / 子宮内膜症 / LPS / エストロゲン / HSP70

Outline of Final Research Achievements

Bacterial contamination hypothesis and sub-clinical uterine infection in women with endometriosis is an innovative research idea in the pathogenesis or pathopaphysiology of endometriosis. Anti-microbial peptides (AMP) such as human beta defensin (HBD) and secretory leukocyte protease inhibitor (SLPI) are found to be regulated by estrogen. Decreased expression of these AMP in endometrium during the menstrual phase could be related to intrauterine microbial colonization and may support our proposed hypothesis. Papers on our new innovative study has been published in Human Reproduction (Khan KN et al., Hum Reprod, 29(11):2446-2456,2014 and Khan KN et al., Hum Reprod 27(12):3417-3424,2012). We presented our new data on bacterial contamination has been recognized and represented in different outstanding domestic and international congresses.Our new concept will open new idea in the development of new therapeutic strategy for the prevention and management of endometriosis.

Research Products

• [Journal Article] 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis (2015)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Reprod Sci Volume: 22 Issue: 5 Pages: 585-594
  • DOI: 10.1177/1933719114556487
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of hepatocyte growth factor-induced epithelial-mesenchymal transition in human adenomyosis (2015)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Biol Reprod Volume: 92 Issue: 2 Pages: 35-35
  • DOI: 10.1095/biolreprod.114.124891
  • Peer Reviewed / Open Access
• [Journal Article] Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis† (2014)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Hum Reprod Volume: 29 Issue: 11 Pages: 2446-2456
  • DOI: 10.1093/humrep/deu222
  • Peer Reviewed
• [Journal Article] Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum. (2014)
  • Author(s): Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki H
  • Journal Title: Human Reproduction Volume: 29(3) Issue: 3 Pages: 462-472
  • DOI: 10.1093/humrep/det438
  • NAID: 120006986656
  • Peer Reviewed
• [Journal Article] Toll-like receptor system and endometriosis. (2013)
  • Author(s): Khan KN, Kitajima M, Fujishita A, Nakashima M, Masuzaki H
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 39(8) Issue: 8 Pages: 1281-1292
  • DOI: 10.1111/jog.12117
  • NAID: 120006986562
  • Peer Reviewed
• [Journal Article] Additive effects of inflammation and stress reaction on Toll-like receptor 4-mediated growth of endometriotic stromal cells. (2013)
  • Author(s): Khan KN, Kitajima M, Inoue T, Tateishi S, Fujishita A, Nakashima M, Masuzaki H
  • Journal Title: Human Reproduction Volume: 28(10) Issue: 10 Pages: 2794-2803
  • DOI: 10.1093/humrep/det280
  • NAID: 120006986038
  • Peer Reviewed
• [Journal Article] Pelvic pain in women with ovarian endometrioma is mostly associated with coexisting peritoneal lesions (2013)
  • Author(s): Khan KN, Kitajima M, Fujishita A, Hiraki K, Matsumoto A, Nakashima M, Masuzaki H
  • Journal Title: Human Reproduction Volume: 28(1) Issue: 1 Pages: 109-118
  • DOI: 10.1093/humrep/des364
  • NAID: 120006985796
  • Peer Reviewed
• [Journal Article] Role of prostaglandin E2 in bacterial growth in women with endometriosis. (2013)
  • Author(s): Khan KN, Kitajima M, Yamaguchi N, Fujishita A, Nakashima M, Ishimaru T, Masuzaki H.
  • Journal Title: Hum Reprod Volume: 27(12) Issue: 12 Pages: 3417-3424
  • DOI: 10.1093/humrep/des331
  • NAID: 120006985795
  • Peer Reviewed
• [Journal Article] Bacterial contamination hypothesis: role of bacterial endotoxin and Toll-like receptor 4 in endometriosis (2012)
  • Author(s): Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Ishimaru T, Masuzaki H
  • Journal Title: Journal of Japan Society of Endometriosis Volume: 33 Pages: 62-67
• [Presentation] Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki H. (2014)
  • Author(s): Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki H.
  • Organizer: 12th World Congress on Endometriosis (WCE)
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 2014-04-30 – 2014-05-03
• [Presentation] Occult endometriosis: an undetectable finding by laparoscopy in normonal peritoneum (2014)
  • Author(s): Khan KN, Fujishita A, Kitajima M, Hiraki K, Nakashima M, Masuzaki H.
  • Organizer: 12th World Congress on Endometriosis (WCE)
  • Place of Presentation: Sao Pualo, Brazil
  • Year and Date: 2014-04-30 – 2014-05-03
  • Invited
• [Presentation] Sub-clinical vaginal and intra-uterine infection in women with endometriosis. (2014)
  • Author(s): Khan KN, Kitajima M, Inoue T, Fujishita A, Nakashima M, Masuzaki H.
  • Organizer: 12th World Congress on Endometriosis (WCE)
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 2014-04-30 – 2014-05-03
• [Presentation] Bacterial contamination hypothesis：細菌性エンドトキシンとToll-like receptor 4 (TLR4)が司る子宮内膜症の増殖・進展に関する新たな病態生理 (2014)
  • Author(s): カーン カレク，北島道夫，井上統夫，藤下 晃，中島正洋, 増崎英明
  • Organizer: 第66回日本産科婦人科学会学術講演会 (synposium)
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20
  • Invited
• [Presentation] Involvement of HGF-induced epithelial-mesenchymal transition in adenomyosis (2014)
  • Author(s): Khan KN, Kitajima M, Fijishita A, Masuzaki H
  • Organizer: 12th World Congress on Endometriosis
  • Place of Presentation: World Trade Center, Sao Paulo, Brazil
  • Invited
• [Presentation] Occult endometriosis: an undetectalbel findings by laparoscopy in normal peritoneum (2014)
  • Author(s): Khan KN, Fijishita A, Kitajima M, Masuzaki H
  • Organizer: 12th World Congress on Endometriosis
  • Place of Presentation: World Trade Center, Sao Paulo, Brazil
  • Invited
• [Presentation] Bacterial contamination hypothesis：細菌性エンドトキシンとToll-like receptor 4 (TLR4)が司る子宮内膜症の増殖・進展に関する新たな病態生理 (2014)
  • Author(s): Khan KN, Kitajima M, Fijishita A, Masuzaki H
  • Organizer: 第６６回日本産科婦人科学会
  • Place of Presentation: 東京国際フォーラム, 東京都千代田区
  • Invited
• [Presentation] 骨盤子宮内膜症の発生に関する新たな視点 (（New insights into peritoneal endometriosis） (2014)
  • Author(s): Khan KN, Kitajima M, Fijishita A, Masuzaki H
  • Organizer: 第３５回日本エンドメトリオーシス学会教育講演抄録
  • Place of Presentation: 城山観光ホテル,鹿児島市
  • Invited
• [Presentation] Role of bacterial endotoxin in endometriosis and its effect on reproductive outcome (2013)
  • Author(s): Khan KN, Kitajima M, Fijishita A, Masuzaki H
  • Organizer: 23rd Asian Oceanic Congress of Obstetrics and Gynecology (AOCOG)
  • Place of Presentation: Centara Grand Hotel, Bangkok, Thailand
  • Invited
• [Presentation] 子宮腺筋症の発生病理における肝細胞増殖因子 (HGF)とE-カドヘリンの関与 (2013)
  • Author(s): カーン カレク，北島道夫，平木宏一，藤下 晃, 増崎英明
  • Organizer: 第 34回エンドメトリオーシス学会 (workshop)
  • Place of Presentation: 栃木
• [Presentation] 子宮筋腫における炎症反応とプロスタグランジン産生―生殖に及ぼす影響につ (2012)
  • Author(s): カーン カレク，北島道夫，平木宏一，藤下 晃，中島正洋, 石丸忠之，増崎英明
  • Organizer: 第3回婦人科ホルモン依存性疾患研究会 (symposium)
  • Place of Presentation: 東京
• [Presentation] 腹腔鏡下に生検した腹膜組織における顕微鏡的内膜症病変に関する検討 (2012)
  • Author(s): カーン カレク，北島道夫，平木宏一, 松本亜由美１, 藤下 晃，中島正洋, 増崎英明
  • Organizer: 第4回Japan Endometriosis Forum (4rd JEF) meeting (invited speaker)
  • Place of Presentation: 千葉
  • Invited
• [Presentation] 多因子疾患である子宮内膜症の真の調節因子とは？ (2012)
  • Author(s): カーン カレク，北島道夫，平木宏一, 藤下 晃，中島正洋, 石丸忠之，増崎英明
  • Organizer: 第57回日本生殖医学会 (educational lecture)
  • Place of Presentation: 長崎
  • Invited
• [Presentation] Adenomyosis; a possible mechanism of gland invagination into myomterium (2012)
  • Author(s): Khan KN, Kitajima M, Hiraki K, Inoue T, Fujishita A, Nakashima M, Masuzaki H
  • Organizer: Workshop on the current status of endometriosis (invited speaker)
  • Place of Presentation: Shanghai, China
  • Invited
• [Presentation] Role of bacterial endotoxin in Toll-like receptor 4-mediated growth of endometriosis (2012)
  • Author(s): Khan KN, Kitajima M, Hiraki H, Inoue T, Fujishita A, Nakashima M, Masuzaki H
  • Organizer: International Conference on Molecular Medicine and Inflammation related to Cancer (MMC)
  • Place of Presentation: Bangkok, Thailand
• [Book] Endometriosis: Pathogenesis and Treatment (2014)
  • Author(s): Khan KN.
  • Publisher: The Springer publishing Co.,
• [Book] Endometriosis: Pathogenesis and Treatment (2014)
  • Author(s): Khan KN.
  • Publisher: Visible and invisible (occult) endometriosis (book chapter).
• [Book] Proceedings of the 4th Congress of the ASPIRE (2013)
  • Author(s): Khan KN, Kitajima M, Masuzaki H
  • Publisher: Role of bacterial endotoxin in endometriosis and its effect on reproductive outcome.
• [Book] Proceedings of the 4th Congress of the ASPIRE (2012)
  • Author(s): Khan KN, Kitajima M, Fujishita A, Masuzaki H
  • Publisher: Role of bacterial endotoxin in endometriosis and its effect on reproductive outcome