Development of treatment and pathogenesis of implantation failure with a focus on the uterine cavity humoral factor

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: OSAMU Inoue 慶應義塾大学, 医学部, 助教 (10464976)
• Co-Investigator(Kenkyū-buntansha): HAMATANI Toshio 慶應義塾大学, 医学部, 講師 (60265882)
• Co-Investigator(Renkei-kenkyūsha): MIYADO Kennzi 独立行政法人国立成育医療研究センター, 生殖・細胞医療研究部, 室長 (60324844)
• Project Period (FY): 2011 – 2013
• Keywords: CD9 / 子宮内腔 / 子宮内膜 / 液性因子 / MMP / 不妊症 / 着床不全 / 炎症

Research Abstract

CD9 is a 24-kD membrane protein, which is localized on endosomes and exosomes as well as cell membranes. Cd9-deficient mouse eggs are unable to fuse with sperm. In this study, we intended that we focused on CD9 of the uterine cavity, and to clarify the role of CD9 in the endometrium. In transgenic mice that were rescued only CD9 expression in the zona pellucida (CD9-/-TG), endometrium of postpartum were not covered with the epithelium, were found extensive adhesions. After measurement of the humoral factors of the uterus cavity fluid, VEGF was decreased in CD9-/-TG compared with wild-type mice, so it was thought that loss of CD9 might interfere with VEGF production. When VEGF was injected in the uterine cavity of CD9 knockout mice, the endometrium was re-epithelialization. CD9 contributed to secretion of VEGF from endometrial epithelial cells, and these results provided the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.

Research Products

• [Journal Article] Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition (2014)
  • Author(s): Kawano N, Miyado K, Yoshii N, Kanai S, Saito H, Miyado M, Inagaki N, Odawara Y, Hamatani T, Umezawa A
  • Journal Title: Sci Rep Volume: 4 Pages: 4701
  • DOI: 10.1038/srep04701
  • Peer Reviewed
• [Journal Article] Derivation of human decidua-like cells from amnion and menstrual blood (2014)
  • Author(s): Sugawara K, Hamatani T, Yamada M, Ogawa S, Kamijo S, Kuji N, Akutsu H, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: Sci Rep Volume: 4 Pages: 4599
  • DOI: 10.1038/srep04599
  • Peer Reviewed
• [Journal Article] β-Catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells (2013)
  • Author(s): Okumura N, Akutsu H, Sugawara T, Miura T, Takezawa Y, Hosoda A, Yoshida K, Ichida JK, Yamada M, Hamatani T, Kuji N, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: Plos One Volume: 8(5) Pages: e63265
  • DOI: 10.1371/journal.pone.0063265
  • Peer Reviewed
• [Journal Article] Successful Implantation After Controlling Matrix Metalloproteinase Activity in Uterine Cavity Flushing (2013)
  • Author(s): Yoshii N, Hamatani T, Inagaki N, Hosaka T, Machiya R, Inoue O, Yoshimura Y, Odawara Y
  • Journal Title: Reprod Biol Endocrinol Pages: 37
  • DOI: 10.1186/1477-7827-11-37
  • Peer Reviewed
• [Journal Article] ART妊娠児の長期予後研究 (2012)
  • Author(s): 久慈直昭,山田満稔,井上治,福永朝子,小川誠司,菅原かな,奥村典子,浜谷敏生,吉村泰典
  • Journal Title: 周産期医学8 Volume: 42巻8号 Pages: 991-1000
• [Journal Article] Human spermatozoal (2012)
  • Author(s): Hamatani T
  • Journal Title: RNAs Fertil Steril Volume: 97 Pages: 275-81
  • DOI: 10.1016/j.fertnstert.2011.12.035
  • Peer Reviewed
• [Journal Article] ART(生殖補助医療)精子・卵子・卵巣の凍結保存とその安全性産婦人科治療 (2011)
  • Author(s): 久慈直昭,井上治,福永朝子,菅原かな,小川誠司,奥村典子,山田満稔,浜谷敏生,吉村泰典
  • Journal Title: 2011年不妊診療のすべて Volume: 102 Pages: 495-500
• [Journal Article] 不妊治療後の妊娠とその予後 (2011)
  • Author(s): 久慈直昭,井上治,福永朝子,菅原かな,小川誠司,奥村典子,内田明花,山田満稔,佐藤卓,浜谷敏生,吉村泰典
  • Journal Title: 産婦人科治療 Volume: 10 Pages: 375-382
• [Presentation] ヒト間葉系幹細胞から子宮内膜間質様細胞への分化誘導 (2013)
  • Author(s): (菅原かな,浜谷敏生,小川誠司,山田満稔,山田朝子,上條慎太郎,竹本崇史,戸田里実,若松修平,久慈直昭,阿久津英憲,梅澤明弘,吉村泰典
  • Organizer: 第58回日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 20131115-16
• [Presentation] 着床前期胚において特異的に発現する新SCAN-zinc finger遺伝子Zfp371の解析 (2013)
  • Author(s): 小川誠司,浜谷敏生,阿久津英憲,山田満稔,奥村典子,菅原かな,井上治,山田朝子,上條慎太郎,久慈直昭,吉村泰典
  • Organizer: 第58回日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 20131115-16
• [Presentation] 着床前期特異的新規遺伝子Kzpiを欠失させた胚性幹細胞(ES細胞)の機能解析 (2013)
  • Author(s): 上條慎太郎,浜谷敏生,阿久津英憲,小川誠司,菅原かな,片岡典子,山田満稔,久慈直昭,吉村泰典
  • Organizer: 第58回日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 20131115-16
• [Presentation] キャピラリー電気泳動-飛行時間型質量分析法(CE-TOFMS)を用いたマウス着床前期胚培養液のメタボローム解析 (2013)
  • Author(s): 若松修平,山田満稔,浜谷敏生,阿久津英憲,竹本崇史,戸田里実,上條慎太郎,小川誠司,菅原かな,久慈直昭,吉村泰典
  • Organizer: 第58回日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-15
• [Presentation] キャピラリー電気泳動-飛行時間型質量分析法(CE-TOFMS)を用いたマウス着床前期胚培養液のメタボローム解析 (2013)
  • Author(s): 浜谷敏生,山田満稔,高梨和美,平山明由,阿久津英憲,福永朝子,小川誠司,菅原かな,篠田幸作,曽我朋義,久慈直昭,梅澤明弘,冨田勝,吉村泰典
  • Organizer: 第54回日本卵子学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-25
• [Presentation] ヒト間葉系幹細胞から子宮内膜間質細胞への分化誘導 (2013)
  • Author(s): 菅原かな,浜谷敏生,小川誠司,山田満稔,奥村典子,福永朝子,井上治,上條慎太郎,久慈直昭,梅澤明弘,青木大輔,吉村泰典
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
  • Year and Date: 2013-05-10
• [Presentation] 着床前期胚において特異的に発現する新規SCAN-zinc finger遺伝子Zfp371の解析 (2013)
  • Author(s): 小川誠司,浜谷敏生,阿久津英憲,山田満稔,奥村典子,菅原かな,井上治,福永朝子,梅澤明弘,久慈直昭,青木大輔,吉村泰典
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
  • Year and Date: 2013-05-10
• [Presentation] 若年性子宮体癌/複雑型子宮内膜異型増殖症に対する妊孕性温存療法後の生殖医療に関する検討 (2012)
  • Author(s): 井上治,浜谷敏生,進伸幸,山上亘,阪埜浩司,内田浩,丸山哲夫,久慈直昭,末岡浩,青木大輔,吉村泰典
  • Organizer: 日本生殖医学会
  • Place of Presentation: 徳島
  • Year and Date: 20121108-09
• [Presentation] 着床前期胚発生に関わる新規遺伝子Zfpiの発現解析 (2012)
  • Author(s): 小川誠司,浜谷敏生,阿久津英憲,山田満稔,奥村典子,菅原かな,井上治,福永朝子,梅澤明弘,久慈直昭,青木大輔,吉村泰典
  • Organizer: 第64回日本産科婦人科学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-04-13
• [Presentation] 着床前期初期から発現し多分化能細胞に特異的に発現する新規転写因子Kzpiの機能解析 (2012)
  • Author(s): 浜谷敏生,山田満稔,阿久津英憲,小川誠司,菅原かな,奥村典子,福永朝子,井上治,梅澤明弘,久慈直昭,青木大輔,吉村泰典
  • Organizer: 第64回日本産科婦人科学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-04-13
• [Presentation] Age- associated alteration of Telomere Biology in mouse oocytes (2011)
  • Author(s): Yamada M, Hamatani T, Akutsu H, Fukunaga T, Kuji N, Umezawa A, Yoshimura Y
  • Organizer: The 67th Annual Meeting of the American Society for Reproductive Medicine (ASRM)
  • Place of Presentation: Orland, USA
  • Year and Date: 20111018-22
• [Presentation] Processing of semen froman HIV- 1- positive male and its use in the IVF- ICSI procedure clinical efficacy (2011)
  • Author(s): Inoue O, Kuji N, Fukunaga T, Ogawa S, Sugawara K, Yamada M, Hamatani T, Hanabusa H, Yoshimura Y, Kato S
  • Organizer: The 27th Annual meeting of the European Society of Human Reproduction and Embryology
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20110703-06
• [Presentation] シンポジウム:卵巣機能異常に起因する不妊治療の最前線:マウス卵の加齢メカニズム (2011)
  • Author(s): 浜谷敏生
  • Organizer: 第56回日本生殖医学会学術講演会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-09
• [Presentation] 着床前期および未分化維持に関わる新規C2H2- zinc finger遺伝子の解析 (2011)
  • Author(s): 近澤奈々,浜谷敏生,山田満稔,阿久津英憲,奥村典子,小川誠司,菅原かな,井上治,福永朝子,久慈直昭,吉村泰典
  • Organizer: 第52回日本哺乳動物卵子学会
  • Place of Presentation: 栃木
  • Year and Date: 2011-05-11