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Establishment and re-establishment of uterine environment for pregnancy success

Research Project

Project/Area Number 16H02584
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Animal production science
Research InstitutionTokai University (2018-2019, 2021)
The University of Tokyo (2016-2017)

Principal Investigator

Imakawa Kazuhiko  東海大学, 総合農学研究所, 教授 (00291956)

Co-Investigator(Kenkyū-buntansha) 草間 和哉  東京薬科大学, 東京薬科大学薬学部, 助教 (30579149)
櫻井 敏博  東京理科大学, 薬学部薬学科, 助教 (70568253)
中尾 洋一  早稲田大学, 理工学術院, 教授 (60282696)
李 俊佑  東京大学, 大学院農学生命科学研究科(農学部), 助教 (10313082)
永岡 謙太郎  東京農工大学, (連合)農学研究科(研究院), 准教授 (60376564)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥40,820,000 (Direct Cost: ¥31,400,000、Indirect Cost: ¥9,420,000)
Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Keywords着床・胎盤形成 / 上皮間葉系転換 / 細胞融合 / トロホブラスト細胞 / 子宮内環境 / 受胎率向上 / 反芻動物 / 子宮内膜 / 遺伝子発現 / タンパク質発現 / 着床 / 妊娠成立 / 構築 / 再構築
Outline of Final Research Achievements

In ruminants, trophoblast cells go through epithelial-mesenchymal transition (EMT) when implanting to the maternal endometrium. As EMT begins, trophoblast cells fuse each other to generate bi-nucleate or multi-nucleated cells, from which pregnancy associated glycoprotein is released. In addition, exosomes, miRNA and lncRNA were found from uterine flushing media and their functions were examined using in vitro uterine epithelial mono-culture or uterine epithelial-trophoblast co-culture systems. miRNA and lncRNA are effective in controling maternal immune system for semi-allogenic trophoblast cells.

Academic Significance and Societal Importance of the Research Achievements

この4年間、反芻動物の着床研究では世界をリードし続けることが出来た。特に、遺伝子・タンパク質発現及びエクソソーム・miRNAやlncRNA分野では先端の研究を続けるだけではなく論文を出し続けた。そのうちの1つ(業績論文9番目)のContinuous model of conceptus implantation to the maternal endometrium.はJ.Endocrinologyで世界で5番目にダウンロードされ、2017年、生殖分野で最も引用回数の多い論文となった。

Report

(5 results)
  • 2021 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (32 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (27 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 27 results,  Open Access: 18 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems2020

    • Author(s)
      Fujiwara Hiroshi、Ono Masanori、Sato Yukiyasu、Imakawa Kazuhiko、Iizuka Takashi、Kagami Kyosuke、Fujiwara Tomoko、Horie Akihito、Tani Hirohiko、Hattori Akira、Daikoku Takiko、Araki Yoshihiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 5 Pages: 1885-1885

    • DOI

      10.3390/ijms21051885

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IFNT-independent effects of intrauterine extracellular vesicles (EVs) in cattle2020

    • Author(s)
      Nakamura Keigo、Kusama Kazuya、Ideta Atsushi、Imakawa Kazuhiko、Hori Masatoshi
    • Journal Title

      Reproduction

      Volume: 159 Issue: 5 Pages: 503-511

    • DOI

      10.1530/rep-19-0314

    • NAID

      130007925663

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roadmap to pregnancy in the first 7 days post-insemination in the cow: Immune crosstalk in the corpus luteum, oviduct, and uterus2020

    • Author(s)
      Talukder AK, Marey MA, Shirasuna K, Kusama K, Shimada M, Imakawa K, Miyamoto A.
    • Journal Title

      Theriogenology

      Volume: 148 Pages: 313-320

    • DOI

      10.1016/j.theriogenology.2020.01.071

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLR2/4 signaling pathway mediates sperminduced inflammation in bovine endometrial epithelial cells in vitro.2019

    • Author(s)
      Ezz MA, Marey MA, Elweza AE, Kawai T, Heppelmann M, Pfarrer C, Balboula AZ, Montaser A, Imakawa K, Zaabel SM, Shimada M, Miyamoto A.
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 4 Pages: e0214516-e0214516

    • DOI

      10.1371/journal.pone.0214516

    • NAID

      120006644937

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of miR-98 in intrauterine extracellular vesicles on maternal immune regulation during the peri-implantation period in cattle2019

    • Author(s)
      Nakamura Keigo、Kusama Kazuya、Ideta Atsushi、Kimura Koji、Hori Masatoshi、Imakawa Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20330-20330

    • DOI

      10.1038/s41598-019-56879-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential roles of metalloproteinases of endometrium-derived exosomes in embryo-maternal crosstalk during implantation.2018

    • Author(s)
      Latifi Z, Fattahi A, Ranjbaran A, Nejabati HR, Imakawa K.
    • Journal Title

      J Cell Physiol

      Volume: 233 Issue: 6 Pages: 4530-4545

    • DOI

      10.1002/jcp.26259

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Induction of immune-related gene expression by seminal exosomes in the porcine endometrium2018

    • Author(s)
      Bai Rulan、Latifi Zeinab、Kusama Kazuya、Nakamura Keigo、Shimada Masayuki、Imakawa Kazuhiko
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Issue: 1 Pages: 1094-1101

    • DOI

      10.1016/j.bbrc.2017.11.100

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intrauterine exosomes are required for bovine conceptus implantation.2018

    • Author(s)
      Kusama その他
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Issue: 1 Pages: 1370-1375

    • DOI

      10.1016/j.bbrc.2017.11.176

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro.2018

    • Author(s)
      Elweza AE, Ezz MA, Acosta TJ, Talukder AK, Shimizu T, Hayakawa H, Shimada M, Imakawa K, Zaghloul AH, Miyamoto A.
    • Journal Title

      Mol Reprod Dev

      Volume: 85 Issue: 3 Pages: 215-226

    • DOI

      10.1002/mrd.22955

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3.2018

    • Author(s)
      Kusama その他
    • Journal Title

      J Cell Biochem

      Volume: - Issue: 6 Pages: 4918-4927

    • DOI

      10.1002/jcb.26721

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of conceptus interferon-tau gene subtypes expressed in the uterus during the peri-implantation period of cattle.2018

    • Author(s)
      Kim MS, Min KS, Seong HH, Kim CL, Jeon IS, Kim SW, Imakawa K.
    • Journal Title

      Anim Reprod Sci

      Volume: 190 Pages: 39-46

    • DOI

      10.1016/j.anireprosci.2018.01.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Integration of molecules to construct the processes of conceptus implantation to the maternal endometrium2018

    • Author(s)
      Imakawa K、Bai R、Kusama K
    • Journal Title

      J Anim Sci

      Volume: 未定 Issue: 7 Pages: 3009-3021

    • DOI

      10.1093/jas/sky103

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evidence that interferon-tau secreted from Day-7 embryo in vivo generates anti-inflammatory immune response in the bovine uterus2018

    • Author(s)
      Rashid MB, Talukder AK, Kusama K, Haneda S, Takedomi T, Yoshino H, Moriyasu S, Matsui M, Shimada M, Imakawa K, Miyamoto A.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 500 Issue: 4 Pages: 879-884

    • DOI

      10.1016/j.bbrc.2018.04.178

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oviduct epithelium induces interferon-tau in bovine Day-4 embryos, which generates an anti-inflammatory response in immune cells.2018

    • Author(s)
      Talukder AK, Rashid MB, Yousef MS, Kusama K, Shimizu T, Shimada M, Suarez SS, Imakawa K, Miyamoto A.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 7580-7580

    • DOI

      10.1038/s41598-018-26224-8

    • NAID

      120006694201

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Day-7 embryos generate an anti-inflammatory immune response in peripheral blood immune cells in superovulated cows.2018

    • Author(s)
      Talukder AK, Rashid MB, Takedomi T, Moriyasu S, Imakawa K, Miyamoto A.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 81 Issue: 2

    • DOI

      10.1111/aji.13069

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Down-regulation of transcription factor OVOL2 contributes to epithelial-mesenchymal transition in a noninvasive type of trophoblast implantation to the maternal endometrium.2018

    • Author(s)
      Bai その他
    • Journal Title

      FASEB J

      Volume: - Issue: 6 Pages: 3371-3384

    • DOI

      10.1096/fj.201701131rr

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel endogenous retrovirus-derived transcript expressed in the bovine placenta is regulated by WNT signaling.2017

    • Author(s)
      Sakurai T, Nakagawa S, Bai H, Bai R, Kusama K, Ideta A, Aoyagi Y, Kaneko K, Iga K, Yasuda J, Miyazawa T, Imakawa K.
    • Journal Title

      Biochemical Journal

      Volume: 474 Issue: 20 Pages: 3499-3512

    • DOI

      10.1042/bcj20170531

    • NAID

      120006649525

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional control of IFNT expression.2017

    • Author(s)
      Ezashi & Imakawa
    • Journal Title

      Reproduction

      Volume: 154 Issue: 5 Pages: F21-F31

    • DOI

      10.1530/rep-17-0330

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Increase in complement iC3b is associated with anti-inflammatory cytokine expression during late pregnancy in mice.2017

    • Author(s)
      Nakamura その他
    • Journal Title

      PLoS One

      Volume: 12 Issue: 5 Pages: e0178442-e0178442

    • DOI

      10.1371/journal.pone.0178442

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thirty years of interferon-tau research; Past, present and future perspective.2017

    • Author(s)
      Imakawa その他
    • Journal Title

      Anim Sci J

      Volume: 88 Issue: 7 Pages: 927-936

    • DOI

      10.1111/asj.12807

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Continuous model of conceptus implantation to the maternal endometrium.2017

    • Author(s)
      Imakawa K, Bai R, Fujiwara H, Ideta A, Aoyagi Y, Kusama K.
    • Journal Title

      Journal of Endocrinology

      Volume: 233 Issue: 1 Pages: R53-R65

    • DOI

      10.1530/joe-16-0490

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.2016

    • Author(s)
      Kusama K, Bai R, Nakamura K, Okada S, Yasuda J, Imakawa K
    • Journal Title

      PLoS One

      Volume: 12 Issue: 2 Pages: e0171858-e0171858

    • DOI

      10.1371/journal.pone.0171858

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Induction of IFNT-stimulated genes by conceptus-derived exosomes during the attachment period.2016

    • Author(s)
      Nakamura K, Kusama K, Bai R, Sakurai T, Isuzugawa K, Suda Y, Imakawa K.
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 6 Pages: e0158278-e0158278

    • DOI

      10.1371/journal.pone.0158278

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of epithelial to mesenchymal transition in bovine conceptuses through the interaction between follistatin and activin A2016

    • Author(s)
      Kazuya Kusama, Rulan Bai, Atsushi Ideta, Yoshito Aoyagi, Kiyoshi Okuda, Kazuhiko Imakawa
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 434 Pages: 81-92

    • DOI

      10.1016/j.mce.2016.06.017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A transcriptional cofactor YAP regulates IFNT expression via transcription factor TEAD in bovine conceptuses.2016

    • Author(s)
      Kusama K., Bai R., Sakurai T., Bai H., Ideta A., Aoyagi Y., Imakawa K.
    • Journal Title

      Domestic Animal Endocrinology

      Volume: 57 Pages: 21-30

    • DOI

      10.1016/j.domaniend.2016.05.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CITED2 modulation of trophoblast cell differentiation: insights from global transcriptome analysis.2016

    • Author(s)
      Imakawa その他
    • Journal Title

      Reproduction

      Volume: 151 Issue: 5 Pages: 509-5016

    • DOI

      10.1530/rep-15-0555

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Placental Development and Endogenous Retroviruses2016

    • Author(s)
      今川和彦、中川草、草間和哉
    • Journal Title

      Uirusu

      Volume: 66 Issue: 1 Pages: 1-10

    • DOI

      10.2222/jsv.66.1

    • NAID

      130006882854

    • ISSN
      0042-6857, 1884-3433
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Bovine endogenous retroviral genes necessary for the trophoblast fusion are up-regulated by PPARG and cAMP after conceptus implantation2018

    • Author(s)
      Kazuya Kusama
    • Organizer
      Society for the Study of Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trophoblast EMT, necessary for conceptus attachment to endometrium in the bovine species, is regulated by transcription factor OVOL2 down-regulation2018

    • Author(s)
      Rulan Bai
    • Organizer
      Society for the Study of Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Continuous model of conceptus implantation to the maternal endometrium.2017

    • Author(s)
      今川和彦
    • Organizer
      Society for the Study of Reproduction
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CITED2 modulates trophoblast stem cell lineage differentiation2016

    • Author(s)
      Imakawa
    • Organizer
      Society of the Study of Reproduction
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 東海大学総合農学研究所 今川和彦

    • URL

      http://www2.kuma.u-tokai.ac.jp/TURIALMR/

    • Related Report
      2019 Annual Research Report

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Published: 2016-04-21   Modified: 2023-01-30  

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