2022 Fiscal Year Final Research Report
Interference of retinoic acid signaling on endocrine disruption
Project/Area Number |
17K20049
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Environmental analyses and evaluation and related fields
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Research Institution | Ritsumeikan University |
Principal Investigator |
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Project Period (FY) |
2017-06-30 – 2023-03-31
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Keywords | 内分泌かく乱 / レチノイン酸シグナル / BPA / NP / iPS / ゼブラフィッシュ |
Outline of Final Research Achievements |
The mechanisms of endocrine disruption are still not comprehensively explained despite many experimental studies over the decades. Based on the hypothesis that retinoic acid (RA) signaling plays an important role in endocrine disruption, I performed experiments using mouse ES cells, human iPS cells, and zebrafish embryos as model systems. Simultaneous addition of RA and Bisphenol A (BPA) enhanced RA signaling in all experimental models. Especially in zebrafish, the simultaneous addition of RA and BPA increased the number of abnormal embryos, neurons, and craniofacial cartilage compared to that of RA alone. This study quantitatively demonstrated that chemicals affect RA signaling and that RA signaling is involved in the mechanism of endocrine disruption.
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Free Research Field |
環境科学
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Academic Significance and Societal Importance of the Research Achievements |
内分泌かく乱現象が生じる原因とそのメカニズムは長年の研究にも関わらず統合的に説明されていなかった。一方で、プラスチック製品や化学物質の増加が近年急増する多様な疾病の原因とされてきた。しかし再現性の高い統一された実験系や実験的根拠はこれまでになかった。本研究ではヒトiPS細胞とゼブラフィッシュ胚を用いて化学物質が生物の基本的な機能に重要な働きを持つレチノイン酸シグナルに影響することを明らかにした。すなわち内分泌かく乱現象にレチノイン酸シグナルが関与することを実験的に示した。さらにヒトiPS細胞が化学物質が生体に与える影響を推定する良いモデルとなりうることを示した。
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