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Analysis of tissue remodeling mechanisms by circulating blood cells during human reproduction

Research Project

Project/Area Number 20390434
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

FUJIWARA Hiroshi  Kyoto University, 医学研究科, 准教授 (30252456)

Co-Investigator(Kenkyū-buntansha) FUJITA Jun  京都大学, 医学研究科, 教授 (50173430)
NISHI Eiichiro  京都大学, 医学研究科, 准教授 (30362528)
NISHIO Takeshi  京都大学, 医学研究科, 助教 (70303790)
HATTORI Akira  京都大学, 薬学研究科, 准教授 (50300893)
Co-Investigator(Renkei-kenkyūsha) TAKAO Yumi  京都大学, 医学研究科, 助教 (20447957)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords組織再構築 / 黄体形成 / 胎盤形成 / 胚着床 / 妊娠 / 末梢血単核球 / 血小板 / 子宮内膜 / 絨毛外栄養膜細胞
Research Abstract

Although it has been widely accepted that adequate endometrial differentiation for embryo implantation is induced by ovarian sex steroid hormones, the precise molecular mechanism(s) concerning human embryo attachment to endometrial epithelium remains unclear. Accordingly, implantation failure in patients treated with in vitro fertilization and embryo transfer has been increasingly focused on in the field of assisted reproductive technology. On the other hand, during the past several decades the mechanisms for establishing maternal immune tolerance against embryo have been investigated in reproductive immunology. Recently, accumulating evidence suggests that activated immune cells actively contribute to establishment of pregnancy. In accordance with it, we found that peripheral blood immune cells positively affect function and differentiation of maternal endometrium and corpus luteum of pregnancy to facilitate embryo implantation during early pregnancy. In addition, platelets were shown to regulate vascular remodeling process in corpus luteum and placental formation. Based on these findings, we have successfully developed a new therapy for patients with implantation failure using autologous peripheral blood immune cells.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (17 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Ephrin A1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells.2011

    • Author(s)
      Fujii H, Fujiwara H, Horie A, Suginami K, Sato Y, Konishi I.
    • Journal Title

      Hum Reprod 26

      Pages: 1163-1170

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation.2011

    • Author(s)
      Fujii H, Fujiwara H, Horie A, Sato Y, Konishi I.
    • Journal Title

      Hum Reprod 26

      Pages: 299-306

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ephrin Al induces intercellular dissociation in Ishikawa cells : possible implication of the Eph-ephrin A system in human embryo implantation.2011

    • Author(s)
      H Fujii, et al.
    • Journal Title

      Human Reproduction

      Volume: 26 Pages: 299-306

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible Contribution of Circulating Blood Cells to Embryo Implantation.2010

    • Author(s)
      Fujiwara H, Ideta A, Araki Y, Takao Y, Sato Y, Horie A, Tsunoda N, Aoyagi Y, Konishi I.
    • Journal Title

      Indian Journal of Physiology and Pharmacology 54

      Pages: 51-59

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of platelets in placentation.2010

    • Author(s)
      Sato Y, Fujiwara H, Konishi I.
    • Journal Title

      Med Mol Morphol 43

      Pages: 129-133

    • NAID

      10026727073

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible Contribution of Circulating Blood Cells to Embryo Implantation2010

    • Author(s)
      H Fujiwara, et al.
    • Journal Title

      Indian Journal of Physiology and Pharmacology

      Volume: 54 Pages: 1236-1239

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of platelets in placentation2010

    • Author(s)
      Y Sato, et al.
    • Journal Title

      Med.Mol.Morphol.

      Volume: 43 Pages: 129-133

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is the zona pellucida an intrinsic source of signals activating maternal recognition of the developing mammalian embryo?2009

    • Author(s)
      Fujiwara H, Araki Y, Toshimori K.
    • Journal Title

      Journal of Reproductive Immunology 81

      Pages: 1-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period?2009

    • Author(s)
      Fujiwara H.
    • Journal Title

      Molecular Human Reproduction 15

      Pages: 335-343

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histidine 379 of Human Laeverin/Aminopeptidase Q, a Nonconserved Residue within the Exopeptidase Motif, Defines Its Distinctive Enzymatic Properties.2009

    • Author(s)
      Maruyama M, Arisaka N, Goto Y, Ohsawa Y, Inoue H, Fujiwara H, Hattori A, Tsujimoto M,
    • Journal Title

      Journal of Biological Chemistry 284

      Pages: 34692-34702

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Is the zona pellucida an intrinsic source of signals activating maternal recognition of the developing mammalian embryo?2009

    • Author(s)
      Fujiwara, et al.
    • Journal Title

      Journal of Reproductive Immunology 81

      Pages: 1-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period?2009

    • Author(s)
      H.Fujiwara
    • Journal Title

      Molecular Human Reproduction 15

      Pages: 335-343

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histidine 379 of Human Laeverin/Aminopeptidase Q, a Nonconserved Residue within the Exopeptidase Motif, Defines Its Distinctive Enzymatic Properties2009

    • Author(s)
      Maruyama, et al.
    • Journal Title

      Journal of Biological Chemistry 284

      Pages: 34692-34702

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Yoshioka S, Fujii S,Ueda M.2008

    • Author(s)
      Takao Y, Fujiwara H
    • Journal Title

      Monoamine oxidase A is highly expressed by the human corpus luteum of pregnancy. Reproduction 136

      Pages: 367-375

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Emergence of highly neurofilament-immunoractive zipper-like axon segment at the transection site in scalpel-cordotomized adult rat.2008

    • Author(s)
      Nishio T, Kawaguchi A, Fujiiwara H.
    • Journal Title

      Neuroscience 155

      Pages: 90-103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 免疫細胞を用いた着床率向上の試み2008

    • Author(s)
      藤原浩
    • Journal Title

      日本産科婦人科学会雑誌 60

    • NAID

      110006943999

    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Journal Article] Monoamine oxidase A is highly expressed by the human corpus luteum of pregnancy2008

    • Author(s)
      Takao, et al.
    • Journal Title

      Reproduction 136

      Pages: 367-375

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emergence of highly neurofilament-immunoractive zipper-like axon segment at the transection site in scalpel-cordotomized adult rat.2008

    • Author(s)
      Nishio, et al.
    • Journal Title

      Neuroscience 155

      Pages: 90-103

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト黄体形成の調節機構2010

    • Author(s)
      藤原浩
    • Organizer
      第15回日本生殖内分泌学会
    • Place of Presentation
      豊中
    • Year and Date
      2010-11-20
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト黄体形成の調節機構2010

    • Author(s)
      藤原浩
    • Organizer
      第15回日本生殖内分泌学会
    • Place of Presentation
      豊中(招待講演)
    • Year and Date
      2010-11-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 着床の基礎と臨床2010

    • Author(s)
      藤原浩
    • Organizer
      第55回日本生殖医学会学術講演会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-12
    • Related Report
      2010 Final Research Report
  • [Presentation] 着床の基礎と臨床2010

    • Author(s)
      藤原浩
    • Organizer
      第55回日本生殖医学会学術講演会
    • Place of Presentation
      徳島(招待講演)
    • Year and Date
      2010-11-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] EphrinA1 induces cell attachment and intercellular dissociation in Ishikawa cells.2010

    • Author(s)
      Fujiwara H, Fujii H, Takao Y, Horie A, Sato Y, Konishi I.
    • Organizer
      14th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Firenze, Italy
    • Year and Date
      2010-03-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Circulating immune cells contribute to embryo implantation during early pregnancy.2009

    • Author(s)
      藤原浩
    • Organizer
      The 3rd International Forum on Repeated IVF Failure
    • Place of Presentation
      Guangzhou, China
    • Year and Date
      2009-11-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Circulating immune cells contribute to embryo implantation during early pregnancy2009

    • Author(s)
      藤原浩
    • Organizer
      The 3rd International Forum on Repeated IVF Failure
    • Place of Presentation
      Guangzhou, China
    • Year and Date
      2009-11-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] 着床をめぐる最近の話題、末梢血免疫細胞による胚着床誘導機構とその臨床応用2009

    • Author(s)
      藤原浩
    • Organizer
      第27回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-08-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 末梢血免疫細胞による胚着床誘導機構とその臨床応用2009

    • Author(s)
      藤原浩
    • Organizer
      第27回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-08-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Circulating blood cell contribution to embryo implantation.2009

    • Author(s)
      藤原浩
    • Organizer
      IUPS Satellite Symposium on Endometrial Receptivity and Blastocyst Implantation
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2009-07-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Circulating blood cell contribution to embryo implantation2009

    • Author(s)
      藤原浩
    • Organizer
      IUPS Satellite Symposium on Endometrial Receptivity and Blastocyst Implantation
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 難治性着床不全不育症に対する治療の試み日本生殖免疫学会2008

    • Author(s)
      藤原浩
    • Organizer
      第23回術集会
    • Place of Presentation
      富山
    • Year and Date
      2008-12-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 難治性着床不全、不育症に対する治療の試み : 自己血液細胞の応用2008

    • Author(s)
      藤原浩
    • Organizer
      日本生殖免疫学会 第23回学術集会
    • Place of Presentation
      富山
    • Year and Date
      2008-12-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Immune cell contribution to systemic crosstalk between mother and embryo around implantation period.2008

    • Author(s)
      藤原浩
    • Organizer
      The st International workshop on Reproductive Biology:"Recent Progresses in Reproductive Biology" SKLAB
    • Place of Presentation
      Beijing, China
    • Year and Date
      2008-10-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Immune cell contribution to systemic crosstalk between mother and embryo around implantation period2008

    • Author(s)
      H. Fujiwara
    • Organizer
      The 1st International workshop on Reproductive Biology : "Recent Progresses in Reproductive Biology" SKLAB 2008
    • Place of Presentation
      Beijing, China
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 周産期免疫、常態と病態、着床誘導機構について日本産婦人科・新生児血液学会2008

    • Author(s)
      藤原浩
    • Organizer
      第18回学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2008-06-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 周産期免疫、常態と病態、着床誘導機構について2008

    • Author(s)
      藤原浩
    • Organizer
      日本産婦人科・新生児血液学会 第18回学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2008-06-28
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 絨毛外栄養膜細胞特異的蛋白2009

    • Inventor(s)
      藤原浩, 他1名
    • Industrial Property Rights Holder
      藤原浩, 他1名
    • Acquisition Date
      2009-07-24
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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