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Immune system of oviduct for very early pregnancy in dairy cattle: A crostalk between sperm/embryo and immune cells

Research Project

Project/Area Number 16H05013
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Animal production science
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

Miyamoto Akio  帯広畜産大学, 畜産学部, 教授 (10192767)

Co-Investigator(Kenkyū-buntansha) 高木 光博  山口大学, 共同獣医学部, 教授 (40271746)
今川 和彦  東京大学, 大学院農学生命科学研究科(農学部), 教授 (00291956)
島田 昌之  広島大学, 生物圏科学研究科, 教授 (20314742)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsウシ / 卵管 / 子宮 / 配偶子 / 免疫応答 / 受胎性 / 免疫細胞 / 精子 / 初期胚 / 免疫システム / 乳牛 / 妊娠 / 免疫
Outline of Final Research Achievements

This study started as a basic research for 4 years on the risks for early embryo death in the oviduct, from the aspect of local immunity of daily cows. From the 2nd year, the study extended to examine both the oviduct and the uterus in parallel. The results indicate that a local immunity in the genital tract starts immediately after artificial insemination by sensing sperm via TLR2, resulting in a weak inflammatory response (Th1). A few numbers of sperm survive and reach the oviduct where sperm are now protected with the anti-inflammatory response (Th2) that completely opposite to that of uterus. After fertilization, very early stage of embryo starts to secrete a small amount of IFNT in the oviduct and later in the uterus that basically regulates a local immunity toward Th2 environment, which prepares a strong immune tolerance for implantation. This series of local immune response to sperm and early embryo is easily disrupted by feed-derived risk factors such as urea and mycotoxin.

Academic Significance and Societal Importance of the Research Achievements

本研究は乳牛をモデルとして、人工授精で精子が入る子宮、受精・初期発生の場である卵管、そして受精卵が戻って着床する子宮に備わる未知の特殊な局所免疫システムについて、新しい基礎概念を構築し、その阻害要因を明らかにした。一連の研究で、母体にとって「非自己」である精子は子宮では攻撃・排除され、卵管では真逆に寛容される免疫システムが存在する、一方で「半非自己」である受精卵は早々に母体に認識され、寛容によって生存性と機能性を支える免疫システムが存在することを初めて実験的に示した。これは、受胎に向けたウシ母体の局所と全身系の免疫システム動態を表すもので、今後の免疫活性化を活用した技術開発の土台となる。

Report

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

    (33 results)

All 2020 2019 2018 2017 2016

All Journal Article (19 results) (of which Int'l Joint Research: 19 results,  Peer Reviewed: 19 results,  Open Access: 17 results,  Acknowledgement Compliant: 3 results) Presentation (13 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Funded Workshop (1 results)

  • [Journal Article] Bovine oviduct epithelial cells suppress the phagocytic activity of neutrophils towards sperm but not for bacteria in vitro: Immunofluorescence and electron microscopic observations.2020

    • Author(s)
      Marey MA, Matsukawa H, Sasaki M, Ezz MA, Yousef MA, Takahashi KI, Miyamoto A.
    • Journal Title

      Histology and Histopathology

      Volume: 35

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation2020

    • Author(s)
      Akthar I, Suarez SS, Morillo VA, Sasaki M, Ezz MA, Takahashi KI, Shimada M, Marey MA, Miyamoto A.
    • Journal Title

      Reproduction

      Volume: 159 Issue: 2 Pages: 181-192

    • DOI

      10.1530/rep-19-0414

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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] Ovulatory follicular fluid induces sperm phagocytosis by neutrophils, but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro.2019

    • Author(s)
      Yousef MS, Abd-Elhafeez HH, Talukder AK, Miyamoto A.
    • Journal Title

      Mol Reprod Dev

      Volume: 86 Issue: 7 Pages: 835-846

    • DOI

      10.1002/mrd.23164

    • 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] Up-regulated mRNA expression of some anti-inflammatory mediators in bovine oviduct epithelial cells by urea in vitro: Cellular pathways by Reactome analysis2019

    • Author(s)
      Kowsar Rasoul、Kowsar Zohre、Miyamoto Akio
    • Journal Title

      Reproductive Biology

      Volume: 19 Issue: 1 Pages: 75-82

    • DOI

      10.1016/j.repbio.2019.01.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Understanding the hidden relations between pro- and anti-inflammatory cytokine genes in bovine oviduct epithelium using a multilayer response surface method.2019

    • Author(s)
      Kowsar R, Keshtegar B, Miyamoto A.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3189-3189

    • DOI

      10.1038/s41598-019-39081-w

    • NAID

      120006603075

    • 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] Urea influences amino acid turnover in bovine cumulus-oocyte complexes, cumulus cells and denuded oocytes, and affects in vitro fertilization outcome.2018

    • Author(s)
      Kowsar R, Iranshahi VN, Sadeghi N, Riasi A, Miyamoto A.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12191-12191

    • DOI

      10.1038/s41598-018-30774-2

    • NAID

      120006533720

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urea changes oocyte competence and gene expression in resultant bovine embryo in vitro.2018

    • Author(s)
      Kowsar R, Izadi F, Sadeghi N, Riasi A, Zadegan FG, Hajian M, Nasr-Esfahani MH, Farrokhpour H, Miyamoto A.
    • Journal Title

      Zygote

      Volume: 26 Issue: 3 Pages: 207-219

    • DOI

      10.1017/s0967199418000102

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] 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
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bovine embryo induces an anti-inflammatory response in uterine epithelial cells and immune cells <i>in vitro</i>: possible involvement of interferon tau as an intermediator2017

    • Author(s)
      Fadhillah, Yoshioka S, Nishimura R, Kiyoshi Okuda
    • Journal Title

      Journal of Reproduction and Development

      Volume: 63 Issue: 4 Pages: 425-434

    • DOI

      10.1262/jrd.2017-056

    • NAID

      130005982816

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An autoregressive logistic model to predict the reciprocal effects of oviductal fluid components on in vitro spermophagy by neutrophils in cattle.2017

    • Author(s)
      Kowsar R, Keshtegar B, Marey MA, Miyamoto A
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4482-4482

    • DOI

      10.1038/s41598-017-04841-z

    • NAID

      120006391001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zearalenone (ZEN) disrupts the anti-inflammatory response of bovine oviductal epithelial cells to sperm in vitro.2017

    • Author(s)
      18) Yousef MS, Takagi M, Talukder A, Marey M, Rasoul K, Abdel-Razek ARK, Shimizu T, Fink-Gremmels J, Miyamoto A
    • Journal Title

      Reproductive Toxicology

      Volume: 74 Pages: 158-163

    • DOI

      10.1016/j.reprotox.2017.09.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urea induces T helper 2 (Th2) type environment at transcriptional level and prostaglandin E2 secretion in bovine oviduct epithelial cells in culture.2016

    • Author(s)
      Kowsar R, Marey MA, Shimizu T, Miyamoto A.
    • Journal Title

      Journal of Dairy Science

      Volume: 99 Issue: 7 Pages: 5844-5850

    • DOI

      10.3168/jds.2016-10874

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Angiotensin II increases sperm phagocytosis by neutrophils in vitro: A possible physiological role in the bovine oviduct.2016

    • Author(s)
      Marey MA, Yousef MS, Liu JH, Morita K, Sasaki M, Hayakawa H, Shimizu T, Miyamoto A.
    • Journal Title

      Molecular Reproduction and Development

      Volume: 83 Issue: 7 Pages: 630-639

    • DOI

      10.1002/mrd.22672

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sperm binding to oviduct epithelial cells enhances TGFB1 and IL10 expressions in epithelial cells as well as neutrophils in vitro: Prostaglandin E2 as a main regulator of anti-inflammatory response in the bovine oviduct.2016

    • Author(s)
      Yousef MS, Marey MA, Hambruch N, Hayakawa H, Shimizu T, Hussien HA, Abdel-Razek ARK, Pfarrer C, Miyamoto A.
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 9 Pages: e0162309-e0162309

    • DOI

      10.1371/journal.pone.0162309

    • NAID

      120006390958

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Sensing sperm by maternal immune crosstalk: A potential mechanism for interfering with fertility in the cow.2019

    • Author(s)
      Akio Miyamoto
    • Organizer
      17th International Conference on Production Disease (ICPD), Bern, Switzerland
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 子宮と卵管の精子認識:免疫システムによる攻撃と寛容2019

    • Author(s)
      宮本明夫
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Involvement of TLR2 in sperm-oviduct epithelium interaction in bovine oviduct ex vivo: Hyaluronan fragmant as a ligand?2019

    • Author(s)
      Vernadyn Almeda Morillo
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sperm penetration into the bovine pre-ovulatory uterine glands induces TNFA in glands and triggers the inflammatory cascade.2019

    • Author(s)
      Ihshan Akthar
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Real-time investigation in vivo of sperm and neutrophils distribution in the bovine uterus after artificial insemination.2019

    • Author(s)
      Mohamed Ali Marey
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pathogens-derived TLR2/4 ligands disrupt the uterine immune response to bovine sperm in vitro.2019

    • Author(s)
      Ibrahim Fouad Elesh
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sensing sperm by bovine uterine epithelial cells via TLR2 and TLR4 signaling pathway in vitro.2018

    • Author(s)
      Akio Miyamoto
    • Organizer
      51st Annual Meeting of Society for the Study of Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interferon-rau is induced in bovine Day-4 embryos by oviduct epithelium, which generates an anti-inflammatory reponse in immune cells.2018

    • Author(s)
      Akio Miyamoto
    • Organizer
      10th International Ruminant Reproduction Symposium 2018 Brazil
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sperm enter bovine uterine glands ex-vivo and initiate a pro-inflammatory response.2018

    • Author(s)
      Ihshan Akthar
    • Organizer
      第111回 日本繁殖生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Bovine day-7 embryo secretes IFNT that generates uterine immunity towards Th 2.2018

    • Author(s)
      Mazlar MD Rashid
    • Organizer
      第124回日本畜産学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Embryo induces immune tolerance in bovine oviduct and uterus in vitro.2017

    • Author(s)
      Talukder AK, Yousef MS, Rashid MB, 粟井健介, 清水隆, 島田昌之, 今川和彦, 宮本明夫
    • Organizer
      日本畜産学会第122回大会
    • Place of Presentation
      神戸大学(兵庫県・神戸市)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Early embryo and epithelial cells interact to induce the anti-inflammatory response on immune cells in bovine oviduct and uterus in vitro.2017

    • Author(s)
      Akio Miyamoto
    • Organizer
      50th Annual Meeting of Society for the Study of Reproduction
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sperm-oviduct interaction ensures the anti-inflammatory environment in the bovine oviduct: A possible role of prostaglandin E2 as a main mediator.2016

    • Author(s)
      Miyamoto A, Yousef MS, Marey MA, Hambruch N, Hayakawa H, Shimizu T, Pfarrer C.
    • Organizer
      49th Society for the Study of Reproduction (SSR)
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Funded Workshop] 51st Annual Meeting of Society for the Study of Reproduction2018

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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