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Adverse outcome pathway concept elucidating the developmental effects of equine estrogens on fish species

Research Project

Project/Area Number 17H01914
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental and ecological symbiosis
Research InstitutionPrefectural University of Kumamoto

Principal Investigator

Arizono KOji  熊本県立大学, 環境共生学部, 教授 (70128148)

Co-Investigator(Kenkyū-buntansha) 冨永 伸明  有明工業高等専門学校, 創造工学科, 教授 (30227631)
石橋 弘志  愛媛大学, 農学研究科, 准教授 (90403857)
吉田 佳督  修文大学, 看護学部, 教授 (90506635)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsエクインエストロゲン / 生態毒性 / 次世代シーケンス / 発生毒性 / パスウェイ解析 / ゼブラフィッシュ / エストロゲン / エクイン / AOP / メダカ / 高電界パルス印加法 / エクイリン / エクイレニン / エストロゲン作用 / 環境汚染 / 動態解析
Outline of Final Research Achievements

The objective of this study was to investigate the adverse outcome pathway (AOP) of equine estrogens (EQs) on developing medaka (Oryzias latipes) and zebrafish (Danio rerio) using in silico and in vivo assays. In silico docking simulation analysis revealed that six EQs interact with the ligand-binding domains of medaka and zebrafish estrogen receptor (ER) subtypes. Our quantitative real-time RT-PCR analyses documented that the mRNA expression levels of CYP19A1b and ChgL in developing zebrafish and medaka responded to various types and concentrations of EQs in a dose response manner. Furthermore, the transcriptome and bioinformatics analyses were performed to investigate the molecular mechanism of developmental toxicity caused by Eq and Eqn. Results revealed that the disruption of several KEGG pathways are involved in the developmental toxicity of EQs in fish embryos. These findings provide insights into the AOP concept elucidating the developmental effects of EQs on fish species.

Academic Significance and Societal Importance of the Research Achievements

本研究では、水環境中のEQs存在実態の解明だけでなく、魚類胚に対するAOPの一端を解明した点に学術的意義がある。また、魚類胚を用いた本研究は、動物福祉・愛護に大きく貢献する。本研究成果は、EQsの生態リスク評価における科学的根拠を提示しただけでなく、AOP研究基盤の高度化にも繋がることが期待される。

Report

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

    (14 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] Choriogenin transcription in medaka embryos and larvae as an alternative model for screening estrogenic endocrine-disrupting chemicals2020

    • Author(s)
      Hiroshi Ishibashi, Masaya Uchida, Yuki Temma, Masashi Hirano, Nobuaki Tominaga, Koji Arizon
    • Journal Title

      Ecotoxicology and Environmental Safety

      Volume: 193 Pages: 110324-110324

    • DOI

      10.1016/j.ecoenv.2020.110324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potential mechanisms underlying embryonic developmental toxicity caused by benzo[a]pyrene in Japanese medaka (Oryzias latipes)2020

    • Author(s)
      Yamaguchi A, Uchida M, Ishibashi H, Hirano M,Ichikawa N Arizono K, Koyama J, Tomonaga N
    • Journal Title

      Chemosphere

      Volume: 242 Pages: 125243-125243

    • DOI

      10.1016/j.chemosphere.2019.125243

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of lithium on developmental toxicity, teratogenicity and transcriptome in medaka embryos2019

    • Author(s)
      Nobuaki Tominaga, Seiya Shino, Masaya Uchida, Hiroshi Ishibashi, Midori Iida, Tadashi Okobira, Kayla Arizono, Noriaki Yoshida, Koji Arizono
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 6 Issue: 2 Pages: 31-36

    • DOI

      10.2131/fts.6.31

    • NAID

      130007593104

    • ISSN
      2189-115X
    • Year and Date
      2019-02-15
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Occurrence and seasonal variation of equine estrogens, equilin and equilenin, in the river water of Japan: Implication with endocrine-disrupting potentials to Japanese medaka (Oryzias latipes)2018

    • Author(s)
      Ishibashi Hiroshi、Uchida Masaya、Yoshimoto Keisuke、Imamura Yuta、Yamamoto Ryoko、Ikenaka Yoshinori、Kawai Masahito、Ichikawa Nobuhiro、Takao Yuji、Tominaga Nobuaki、Ishibashi Yasuhiro、Arizono Koji
    • Journal Title

      Environmental Pollution

      Volume: 239 Pages: 281-288

    • DOI

      10.1016/j.envpol.2018.04.029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Occurrence and seasonal variation of equine estrogens, equilin and equilenin, in the river water of Japan: implication with endocrine-disrupting potentials to Japanese medaka (Oryzias latipes)2018

    • Author(s)
      Hiroshi Ishibashi, Masaya Uchida , Keisuke Yoshimoto, Yuta Imamura, Ryoko Yamamoto, Yoshinori Ikenaka , Masahito Kawai , Nobuhiro Ichikawa , Yuji Takao , Nobuaki Tominaga, Yasuhiro Ishibashi, Koji Arizono
    • Journal Title

      Environmental Pollution

      Volume: 239 Pages: 281-288

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In vivo and in silico analyses of estrogenic potential of equine estrogens in zebrafish (Danio rerio)2019

    • Author(s)
      Koji Arizono, Masashi Hirano, Hiroshi Ishibashi, Masaya Uchida, Nobuaki Tominaga and Akira Kubota
    • Organizer
      SETAC-North America 40th Annual Meeting(国際学会)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In silico及びin vivo解析を用いたエクインエストロゲン類のエストロゲン様作用の評価 -ヒメダカ及びゼブラフィッシュに対する作用の比較2019

    • Author(s)
      内田雅也, 久保田彰,平野将司,石橋弘志,石橋康弘,冨永伸明,有薗幸司
    • Organizer
      環境ホルモン学会第22回研究発表会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analyses of embryonic CYP19A1b gene expression and estrogen receptor binding ability by equine estrogens in zebrafish (Danio rerio)2019

    • Author(s)
      Koji Arizono, Masashi Hirano, Hiroshi Ishibashi, Masaya Uchida, Nobuaki Tominaga and Akira Kubota
    • Organizer
      環境ホルモン学会第22回研究発表会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Equine Estrogens Concentrations in Aquatic Environment and Their Endocrine Disrupting Potentials for Fish2018

    • Author(s)
      Koji Arizono
    • Organizer
      11th International Conference on Environmental Health Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 17βestradiolによるメダカ胚エストロゲン応答遺伝子の発現解析2018

    • Author(s)
      石橋弘志、内田雅也、天満柚来 平野将司、冨永伸明、有薗幸司
    • Organizer
      環境ホルモン学会第21回研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] メダカ初期胚を用いたエクインエストロゲン類のトランスクリプトーム解析2018

    • Author(s)
      内田雅也、石橋弘志、平野将司、福島聡、石橋康弘、冨永伸明、有薗幸司
    • Organizer
      環境ホルモン学会第21回研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of equine estrogens on medaka embryos2018

    • Author(s)
      K Arizono, M Uchida, S. Fukushima, H. Ishibashi, N. Tominaga
    • Organizer
      SETAC-North America 39th Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EPRODUCTIVE AND TRANSGENERATIONAL EFFECTS OF EQUILIN IN JAPANESE MEDAKA (ORYZIAS LATIPES) AND HEPATIC ESTROGEN-RESPONSIVE GENE EXPRESSION2017

    • Author(s)
      Hiroshi Ishibashi, Masaya Uchida, Keisuke Yoshimoto, Ryoko Yamamoto, Nobuaki Tominaga, Yasuhiro Ishibashi, Koji Arizono
    • Organizer
      PRIMO19
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reproductive and transgenerational effects of equilin in Japanese medaka and hepatic estrogen-responsive gene expression2017

    • Author(s)
      Hiroshi Ishibashi, Masaya Uchida, Keisuke Yoshimoto, Ryoko Yamamoto, Nobuaki Tominaga, Yasuhiro Ishibashi, Koji Arizono
    • Organizer
      2017 SETAC North Amerika
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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