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ヒト卵子再生と卵胞完全体外培養による新たな不妊治療法の開発

Publicly Offered Research

Project AreaMechanisms regulating gamete formation in animals
Project/Area Number 26114510
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

河村 和弘  聖マリアンナ医科大学, 医学部, 准教授 (10344756)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords生殖細胞 / 卵巣髄質 / 組織分散 / 卵子 / 卵子再生 / 減数分裂誘導 / 生殖細胞様細胞 / カルシウムシグナル
Outline of Annual Research Achievements

哺乳動物の卵子は胎児期の卵巣内で作られ、出生後には作られないと考えられてきた。近年、Tillyらの研究グループがヒト卵巣皮質に卵子幹細胞が存在することを示唆したが、その後多くの研究グループによって、再現性がないことが指摘された。
我々は、ヒト卵巣の髄質細胞を分散することで生殖細胞特異的な遺伝子であるPRDM1陽性細胞が発生することをすでに突き止め、本年度は再現性のある卵子への分化誘導法の開発を行い、減数分裂期までの分化誘導に成功した。
具体的には、三段階の培養法によって出生後卵巣由来生殖系列細胞(PostOGC)を減数分裂期へと誘導する。一段階目は、BMP4とActivinAによりPRDM1陽性のPostOGC細胞をDAZL陽性細胞へ分化させる。このDAZL陽性細胞は始原生殖細胞が発現するSSEA1とCD61の両陽性であることを確認している。
二段階目は、Forskolin、Ciglitazone、wnt agonist、SC79の4種類の活性化因子により減数分裂期直前のSCP3陽性細胞へと分化させる。分化したPostOGCはSCP3陽性であるものの、SCP3が細胞質に局在しているのが特徴的である。
三段階目は、PMA、Ciglitazone、SC79、2-HGを添加した培養液を用いる。この三段階目の培養によってSCP3が核へ移行し、減数分裂時の染色体に特異的なSCP3の局在となる。
これらの段階培養法は、それぞれ6日間行う。さらに培養6日目に出現するSSEA1,CD61両陽性細胞を単離して、第二、第三段階目の培養法で培養しても同様の結果が得られることから、卵巣髄質内に存在するPostOGCは適切な環境下で減数分裂期へと到達する能力を有していることが初めて明らかになった。これらの結果から、PostOGCを適切に分化誘導することで、卵巣から卵子を再生することが可能になると期待される。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (46 results)

All 2017 2016 2015 2014

All Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Open Access: 8 results,  Peer Reviewed: 7 results,  Acknowledgement Compliant: 5 results) Presentation (28 results) (of which Int'l Joint Research: 14 results,  Invited: 27 results) Book (5 results)

  • [Journal Article] isorganization of the germ cell pool leads to primary ovarian insufficiency.2017

    • Author(s)
      Kawashima I, Kawamura K
    • Journal Title

      Reproduction

      Volume: 印刷中 Issue: 6 Pages: R205-R213

    • DOI

      10.1530/rep-17-0015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 早発卵巣不全(早発閉経)の新たな不妊治療2016

    • Author(s)
      河村和弘
    • Journal Title

      日本医師会雑誌

      Volume: 144 Pages: 2096-2097

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Journal Article] 卵胞活性化療法2016

    • Author(s)
      河村和弘
    • Journal Title

      Hormone Frontier in Gynecology

      Volume: 23 Pages: 63-67

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 早発閉経の治療2016

    • Author(s)
      河村和弘
    • Journal Title

      産科と婦人科

      Volume: 83 Pages: 1184-1189

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 早発閉経2016

    • Author(s)
      河村和弘
    • Journal Title

      臨床 婦人科産科

      Volume: 70 Pages: 1137-1142

    • Related Report
      2015 Annual Research Report
  • [Journal Article] がん治療後の卵巣機能不全と妊娠2016

    • Author(s)
      河村和弘
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 68 Pages: 3029-3033

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 卵胞発育を理解するー知っておくべき基礎知識(卵胞発育異常の病態と治療) 早発閉経2016

    • Author(s)
      河村和弘
    • Journal Title

      臨床婦人科産科

      Volume: 70 Pages: 1137-1142

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Activation of dormant follicles: a new treatment for premature ovarian failure?2016

    • Author(s)
      Kawamura K, Kawamura Nanami, Hsueh AJ
    • Journal Title

      Curr Opin Obstet Gynecol

      Volume: in press Issue: 3 Pages: 217-222

    • DOI

      10.1097/gco.0000000000000268

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients.2016

    • Author(s)
      Zhai J, Yao G, Dong F, Bu Z, Cheng Y, Sato Y, Hu L, Zhang Y, Wang J, Dai S, Li J, Sun J, Hsueh AJ, Kawamura K, Sun Y
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 101 Issue: 11 Pages: 4405-4412

    • DOI

      10.1210/jc.2016-1589

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Intraovarian control of early folliculogenesis.2015

    • Author(s)
      Hsueh AJ, Kawamura K, Cheng Y, Fauser BC
    • Journal Title

      Endocr Rev

      Volume: 36 Issue: 1 Pages: 1-24

    • DOI

      10.1210/er.2014-1020

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of menstrual cycle phase and AMH levels in breast cancer patients whose ovarian tissue was cryopreserved for oncofertility treatment.2015

    • Author(s)
      Takae S, Sugishita Y, Yoshioka N, Hoshina M, Horage Y, Sato Y, Nishijima C, Kawamura K, Suzuki N
    • Journal Title

      J Assist Reprod Genet

      Volume: 32 Issue: 2 Pages: 305-312

    • DOI

      10.1007/s10815-014-0392-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency.2015

    • Author(s)
      Suzuki N, Yoshioka N, Takae S, SugishitaY, Tamura M, Hashimoto S, Morimoto Y, Kawamura K
    • Journal Title

      Hum Reprod

      Volume: 30 Issue: 3 Pages: 608-615

    • DOI

      10.1093/humrep/deu353

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Actin polymerization-enhancing drugs promote ovarian follicle growth mediated by the Hippo signaling effector YAP.2015

    • Author(s)
      Cheng Y, Feng Y, Jansson L, Sato Y, Deguchi M,Kawamura K, Hsueh AJ
    • Journal Title

      FASEB J

      Volume: 29 Issue: 6 Pages: 2423-2430

    • DOI

      10.1096/fj.14-267856

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Establishment of Novel Infertility Treatment for Patients with Primary Ovarian Insufficiency: In Vitro Activation [IVA]:2017

    • Author(s)
      Kawamura K
    • Organizer
      2nd Upper Egypt Assisted Reproductive Conference
    • Place of Presentation
      Egypt・Cairo
    • Year and Date
      2017-02-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recent progress in IVA as a new infertility treatments of patients with primary ovarian insufficiency2017

    • Author(s)
      Kawamura K
    • Organizer
      the 29th conference of the Korean Society for Assisted Reproduction
    • Place of Presentation
      Korean・Soul
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 喫煙は早発卵巣不全の発症因子、増悪因子となりうるか2017

    • Author(s)
      河村和弘
    • Organizer
      日本生殖再生医学会第12回学術集会
    • Place of Presentation
      東京・千代田(シェーンバッハサボー)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] In vitro follicle activation2016

    • Author(s)
      Kawamura K
    • Organizer
      Turkish Society Reproductive Medicine Congress 2016
    • Place of Presentation
      Turkey・ANTALYA
    • Year and Date
      2016-11-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New fertility treatments (IVA) In vitro activation :A new infertility treatment for patients with primary ovarian insufficiency(POI)2016

    • Author(s)
      Kawamura K
    • Organizer
      OVARIAN CLUB VIII BUILDING A BRIDGE BETWEEN SCIENCE AND CRINICAL PRACTICE
    • Place of Presentation
      France・Paris
    • Year and Date
      2016-11-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵巣の生殖機能再生:卵胞活性化療法(In vitro activation)の臨床試験と卵巣潅流培養への展開2016

    • Author(s)
      河村和弘
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山・富山(富山国際会議場)
    • Year and Date
      2016-04-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] In-vitro activation (IVA): the answer to the aging ovary?2016

    • Author(s)
      Kawamura K
    • Organizer
      The 6th CONGRESS OG THE ASIA PACIFIC INITIATIVE ON REPRODUCTION
    • Place of Presentation
      Indonesia・Jakarta
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん治療後の卵巣機能不全と妊娠2016

    • Author(s)
      河村和弘
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京・千代田(東京国際フォーラム)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] New infertility treatments(IVA: in vitro activation) of patients with primary ovarian insufficiency (POI)2016

    • Author(s)
      Kawamura K
    • Organizer
      The XI TURKISH GERMAN GYNECOLOGIC CONGRESS
    • Place of Presentation
      Turkey・ANTALYA
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Fertility preservation patients with primary ovarian insufficiency2016

    • Author(s)
      Kawamura K
    • Organizer
      12th scientific meeting of the GRECOT(GROUP DE RECHERCHE ET D’ETUDE SUR LA CRYOCONSERVTION DE L’OVAIRE ET DU TESTICULE)
    • Place of Presentation
      France・Paris
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵巣への物理的刺激によるHippoシグナル抑制を応用した新規卵胞発育誘導法のためのデバイス開発2016

    • Author(s)
      河村和弘
    • Organizer
      次世代医療システム産業フォーラム
    • Place of Presentation
      大阪・大阪(大阪商工会議所)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] P13K regulation of dormant follicle activation2016

    • Author(s)
      Kawamura K
    • Organizer
      Society for Reproduction and Fertility ANNUAL CONFERENCE2016
    • Place of Presentation
      England(University of WINCHESTER)
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 卵巣機能不全の新たな治療戦絡:特発性から子宮内膜症術後症例まで2016

    • Author(s)
      河村和弘
    • Organizer
      青葉区産婦人科医会
    • Place of Presentation
      神奈川・横浜(神奈川県総合医療会館)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 卵胞活性化技術とヒトへの応用2016

    • Author(s)
      河村和弘
    • Organizer
      第57回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      東京・三鷹(杏林大学井の頭キャンパス)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 卵胞活性化療法のfrom bench to bed and back2016

    • Author(s)
      河村和弘
    • Organizer
      第34回日本受精着床学会総会・学術講演会
    • Place of Presentation
      長野・軽井沢(軽井沢プリンスホテルウエスト)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 卵巣機能不全の新しい治療戦略2016

    • Author(s)
      河村和弘
    • Organizer
      第34回日本受精着床学会総会・学術講演会
    • Place of Presentation
      長野・軽井沢(軽井沢プリンスホテルウエスト)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Advances in treating ovarian failure: In-vitro activation2016

    • Author(s)
      Kawamura K
    • Organizer
      2nd International Congress Meeting the Experts
    • Place of Presentation
      Spain・Alicante
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 早発卵巣不全の最新治療2016

    • Author(s)
      河村和弘
    • Organizer
      第14回播磨産婦人科内分泌研究会
    • Place of Presentation
      兵庫・姫路(姫路キャッスルグランヴィリオホテル)
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 老化した卵子、胚の質の改善剤:CXCL5-CXCR2シグナル制御薬2016

    • Author(s)
      河村和弘
    • Organizer
      医薬・診断 新技術説明会
    • Place of Presentation
      東京・千代田(JST東京本部別館ホール)
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] POIの卵胞活性化法を用いた新たな不妊治療戦略2015

    • Author(s)
      河村和弘
    • Organizer
      第11回ART生涯研修コース
    • Place of Presentation
      東京
    • Year and Date
      2015-03-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 早発卵巣不全の新たな治療戦略:卵胞活性化療法2015

    • Author(s)
      河村和弘
    • Organizer
      第19回福岡生殖医学懇話会
    • Place of Presentation
      福岡
    • Year and Date
      2015-02-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Aktシグナル活性化とHippoシグナル抑制による早発卵巣不全患者の卵胞発育の新たな不妊治療法の開発2015

    • Author(s)
      河村和弘
    • Organizer
      第19回日本生殖内分泌学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-01-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 卵胞活性化による早発卵巣不全の新しい不妊治療2014

    • Author(s)
      河村和弘
    • Organizer
      第59回日本生殖医学会学術講演会・総会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] New infertility treatments of patients with primary ovarian insufficiency (POI)2014

    • Author(s)
      Kazuhiro Kawamura
    • Organizer
      Ovarian Follicles from Basic Science to Clinical Application
    • Place of Presentation
      Palo Alto
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ovarian Grafting Video2014

    • Author(s)
      Kazuhiro Kawamura
    • Organizer
      Ovarian Follicles from Basic Science to Clinical Application
    • Place of Presentation
      Palo Alto
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vitro activation as a tool for treating infertility related to premature ovarian failure.2014

    • Author(s)
      Kazuhiro Kawamura
    • Organizer
      The 7 th World Congress on Mild Approaches in Assisted Reproduction
    • Place of Presentation
      Sydoney
    • Year and Date
      2014-09-10
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Successful pregnancies and a birth after in vitro activation (IVA) of ovarian follicles in patients with primary ovarian insufficiency.2014

    • Author(s)
      Kazuhiro Kawamura
    • Organizer
      The 66 th Annual meeting of the Korean Society for Reproductive Medicine
    • Place of Presentation
      Seoul
    • Year and Date
      2014-05-03
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 早発卵巣不全患者のIVA (in vitro activation)による卵胞活性化―卵巣自家移植の臨床成績2014

    • Author(s)
      河村和弘
    • Organizer
      第66回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-18
    • Related Report
      2014 Annual Research Report
  • [Book] 基礎からわかる女性内分泌 早発卵巣不全の病態と診断2016

    • Author(s)
      河村和弘
    • Publisher
      診断と治療社
    • Related Report
      2015 Annual Research Report
  • [Book] 基礎からわかる女性内分泌 早発卵巣不全の治療2016

    • Author(s)
      河村和弘
    • Publisher
      診断と治療社
    • Related Report
      2015 Annual Research Report
  • [Book] 不妊・不育診療指針The perfect Guide for Infertility 早発卵巣不全(POI)2016

    • Author(s)
      河村和弘
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report
  • [Book] 女性内分泌クリニカルクエスチョン90 Q37 卵巣機能不全に影響する抗がん剤はどのようなものがある?2016

    • Author(s)
      河村和弘、河村七美
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report
  • [Book] 女性内分泌クリニカルクエスチョン90 Q38 POIに対する排卵誘発法を成功させるには?2016

    • Author(s)
      河村和弘、河村七美
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2019-12-27  

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