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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H01914
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental and ecological symbiosis
• Research Institution: Prefectural 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
• 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

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.

Free Research Field

環境毒性

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。