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Intrauterine environment during implantation in bovine pregnancy.

Research Project

Project/Area Number 19H03111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42010:Animal production science-related
Research InstitutionOhu University

Principal Investigator

Sakurai Toshihiro  奥羽大学, 薬学部, 准教授 (70568253)

Co-Investigator(Kenkyū-buntansha) 草間 和哉  東京薬科大学, 薬学部, 助教 (30579149)
唄 花子  北海道大学, 農学研究院, 助教 (60775443)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywordsウシ / 子宮 / 着床 / 生体外モデル / 子宮灌流液 / 末梢血単核球 / IL-6 / IL-10 / 子宮内環境 / 子宮オルガノイド / 妊娠補助剤開発 / 生体外モデル樹立 / 着床成立 / PBMC / オルガノイド
Outline of Research at the Start

受精胚と母体子宮間のコミュニケーション不足のために生じる胚死滅を低減し、受胎を確実に成立させ、畜産・酪農の生産力を強化する技術開発を目的とする。胚死滅予防法および受胎率向上法の確立を目指し、受胎が成立する子宮内環境を明らかにする。その際、申請者が開発した、ウシの着床過程を再現する生体外モデルを利用する。生体外モデルを用いて着床期の子宮灌流液中の着床に寄与する因子の同定を行う。その際、生体外モデルの改良として子宮オルガノイドの作製を行う。また、申請者が見出した末梢血単核球の子宮内投与による胚死滅低減機序を解明し、生産現場で利用できる技術として確立するための知見を得る。

Outline of Final Research Achievements

In order to clarify what is different in the intrauterine environment of inseminated cows from that of fertile cows, it is necessary to spatiotemporal analyze the intrauterine environment. Using the in vitro implantation model, we, therefore, identified the factors contributing to implantation to clarify the intrauterine environment. We found Versican, which is an extracellular matrix involved in implantation. We also found IL-6 present in the uterine flushing, that is a cytokine contributes to conceptus elongation. We also found that high expression of SNX5 in serum of ewes on day 22 of gestation could be a marker of embryo loss. It was predicted that the concentration gradient of some cytokine is formed by Versican during the bovine implantation process, thereby contributing to the selective accumulation of immune cells in utero and embryo elongation.

Academic Significance and Societal Importance of the Research Achievements

分娩間隔の長期化や繁殖成績の低下により、本邦における子牛の生産が減少している。また、また、現在ウシの繁殖は、凍結精液を子宮内に投与する人工授精によって成り立っているがその受胎率は年々減少している。家畜の生産性の向上は喫緊の課題でありながらも、着床が成立するための子宮内環境・条件を明らかにする研究は世界的に不足している。生体外着床モデルを用いた検討は、着床成立に寄与する因子を時間・空間的に解析し、同定できることが示され、この分野の発展に欠かせないツールであることを証明した。今後、このツールを利用し、着床に寄与する因子群の同定を行っていく。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (7 results)

All 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Characterization of Serum Metabolome and Proteome Profiles Identifies SNX5 Specific for Pregnancy Failure in Holstein Heifers2022

    • Author(s)
      Kusama Kazuya、Bai Rulan、Matsuno Yuta、Ideta Atsushi、Sakurai Toshihiro、Nagaoka Kentaro、Hori Masatoshi、Imakawa Kazuhiko
    • Journal Title

      Life

      Volume: 12 Issue: 2 Pages: 309-309

    • DOI

      10.3390/life12020309

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat stress induces oxidative stress and activates the KEAP1-NFE2L2-ARE pathway in bovine endometrial epithelial cells2021

    • Author(s)
      Murata Hirona, Kunii Hiroki ,Kusama Kazuya, Sakurai Toshihiro, Bai Hanako、Kawahara Manabu、Takahashi Masashi
    • Journal Title

      Biology of Reproduction

      Volume: 105 Issue: 5 Pages: 1114-1125

    • DOI

      10.1093/biolre/ioab143

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice2021

    • Author(s)
      Ekuban Frederick Adams、Zong Cai、Takikawa Madoka、Morikawa Kota、Sakurai Toshihiro、Ichihara Sahoko、Itoh Ken、Yamamoto Masayuki、Ohsako Seiichiroh、Ichihara Gaku
    • Journal Title

      Toxicology

      Volume: 456 Pages: 152785-152785

    • DOI

      10.1016/j.tox.2021.152785

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 1,2-Dichloropropane induces γ-H2AX expression in human cholangiocytes only in the presence of macrophages2021

    • Author(s)
      Takizawa Ryoya、Ichihara Sahoko、Zong Cai、Kinoshita Kazuo、Sakurai Toshihiro、Ikegami Akihiko、Mise Nathan、Ichihara Gaku
    • Journal Title

      Toxicology Letters

      Volume: 349 Pages: 134-144

    • DOI

      10.1016/j.toxlet.2021.06.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exposure to acrylamide decreases noradrenergic axons in rat brain2020

    • Author(s)
      Zhang Lingyi、Hara Satoshi、Ichinose Hiroshi、Nagashima Daichi、Morita Kyo、Sakurai Toshihiro、Ichihara Sahoko、Ichihara Gaku
    • Journal Title

      NeuroToxicology

      Volume: 78 Pages: 127-133

    • DOI

      10.1016/j.neuro.2020.03.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Proteomic analysis of liver proteins of mice exposed to 1,2-dichloropropane.2020

    • Author(s)
      Zhang X, Morikawa K, Mori Y, Zong C, Zhang L, Garner E, Huang C, Wu W, Chang J, Nagashima D, Sakurai T, Ichihara S, Oikawa S, Ichihara G.
    • Journal Title

      Arch Toxicol.

      Volume: 94 Issue: 8 Pages: 2691-2705

    • DOI

      10.1007/s00204-020-02785-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 桂皮熱水抽出物曝露による 不死化ヒト初期絨毛株HTR8細胞の浸潤抑制2021

    • Author(s)
      櫻井敏博、阿部惇平、吉江幹浩、田村和宏、 吉田さくら、大嶋直浩、羽田紀康
    • Organizer
      日本胎盤学会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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