The molecular analysis of placental abruption using in vitro placental model

• Project/Area Number: 23659779
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: KIMURA Tadashi 大阪大学, 医学(系)研究科(研究院), 教授 (90240845)
• Co-Investigator(Kenkyū-buntansha): SAWADA Kenjiro 大阪大学, 医学系研究科, 講師 (00452392) ; MABUCHI Seiji 大阪大学, 医学系研究科, 助教 (00452441) ; ISOBE Aki 大阪大学, 医学系研究科, 助教 (60397619) ; HASHIMOTO Kae 大阪大学, 医学系研究科, 助教 (90612078)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 常位胎盤早期剥離 / 前期破水 / インターロイキン / プロスタグランジン / 絨毛羊膜炎 / 絨毛細胞 / 脱落膜細胞 / 低酸素刺激 / Eカドヘリン

Research Abstract

Intrauterine infection is a key trigger of placental abruption. In order to analyze the potential role of inflammatory cytokines in this pathogenesis, we examined the expressional pattern of various cytokines in placentae complicated with severe chorioamnionitis (CAM) and found that IL-6 is mainly expressed in macrophages in villous mesenchyme. Using an experimental lipopolysaccharide (LPS)-induced PTD model, the therapeutic potential of targeting this cytokine was investigated. Anti-IL-6 receptor antibody (MR16-1) was delivered before LPS treatment. Mice in the MR16-1 group had a significantly lower rate of PTD (17%) than 53% in the controls. As a result, MR16-1 treatment significantly prolonged the gestational period without any apparent adverse events on the mice and their pups. Thus, targeting IL-6 signaling can be a promising option for the prevention of placental abruption and needs to be further explored for future clinical application.

Research Products

• [Journal Article] Targeting interleukin-6 receptor inhibits preterm delivery induced by inflammation (2013)
  • Author(s): Wakabayashi, A. Sawada, K. Nakayama, M. Toda, A. Kimoto, A. Mabuchi, S. Kinose, Y. Nakamura, K. Takahashi, K. Kurachi, H. Kimura, T
  • Journal Title: Mol Hum Reprod Volume: 19 Pages: 718-726
• [Journal Article] Targeting interleukin-6 receptor inhibits preterm delivery induced by inflammation (2013)
  • Author(s): Wakabayashi, A. Sawada, K. Nakayama, M. Toda, A. Kimoto, A. Mabuchi, S. Kinose, Y. Nakamura, K. Takahashi, K. Kurachi, H. Kimura, T.
  • Journal Title: Mol Hum Reprod Volume: 19 Issue: 11 Pages: 718-26
  • DOI: 10.1093/molehr/gat057
  • Peer Reviewed
• [Journal Article] 前置胎盤の帝王切開-術式および工夫- (2012)
  • Author(s): 木瀬康人、木村正
  • Journal Title: 臨床婦人科産科 Volume: 66 Pages: 731-735
  • Peer Reviewed
• [Presentation] 卵巣癌組織におけるインターロイキン6(IL-6)とその受容体の発現が予後に与える影響の解析 (2013)
  • Author(s): 磯部 晶. 澤田健二郎. 小倉寛則. 木瀬康人. 川島英理子. 牧野 弘. 水野智子.木村 正. 森重健一郎
  • Organizer: 第65回日本産科婦人科学会
  • Place of Presentation: 札幌
• [Presentation] 感染性早産に対するIL‐6 に焦点を当てた分子標的治療の可能性の検討 (2013)
  • Author(s): 澤田健二郎
  • Organizer: 第21回日本胎盤学会
  • Place of Presentation: 名古屋
• [Presentation] 感染性早産に対する IL‐6 に焦点を当てた分子標的治療の可能性の検討 (2013)
  • Author(s): 澤田 健二郎
  • Organizer: 第21回日本胎盤学会
  • Place of Presentation: 名古屋
• [Presentation] 上皮性卵巣癌におけるmTOR complex 2 (mTORC2) の発現とその臨床的意義の検討 (2012)
  • Author(s): 久松武志、馬淵誠士、河野まひる、橋本香映、磯部晶、澤田健二郎、木村正
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 兵庫
• [Presentation] 上皮性卵巣癌におけるmTOR complex 2 (mTORC2) の発現とその臨床的意義の検討 (2012)
  • Author(s): 久松武志、馬淵誠士、河野まひる、橋本香映、磯部晶、澤田健二郎、木村正
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京
• [Presentation] 早産に対する新たな分子標的治療の可能性の検討 (2011)
  • Author(s): 若林敦子
  • Organizer: 第63回日本産科婦人科学会
  • Place of Presentation: 大阪