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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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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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 / レチノイン酸 / 化学物質 / 頭部形成 / 神経形成 / 頭蓋軟骨 / iPSC / トランスクリプトーム / ヒトiPS細胞 / 頭蓋軟骨形成 / トランスクリプトーム解析 / 発現解析 / iPS細胞 / ゼブラフィッシュ 胚 / 細胞分化 / 形態形成 / in situ hybridizaion / 幹細胞分化 / 琵琶湖固有種 / ホンモロコ / in vitro精子分化 / 魚類 |
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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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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Report
(7 results)
Research Products
(29 results)
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[Journal Article] Identification of TEKTIN1-expressing multiciliated cells during spontaneous differentiation of non-human primate embryonic stem cells2023
Author(s)
Nishie T., Ohta Y., Shirai E., Higaki S., Shimozawa N., Narita K., Kawaguchi K., Tanaka H., Mori C., Tanaka T., Hirabayashi M., Suemori H., Kurisaki A., Tooyama I., Asano S., Takeda S., Takada T.
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Journal Title
Genes to Cells
Volume: -
Issue: 7
Pages: 516-525
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nonyophenol reduced the number of haploids in in vitro spermatogenesis of the endangered cyprinid Gnathopogon caerulescens2023
Author(s)
Nishie T., Komaru. A., Shiroguchi S., Yamaizumi T., Ono Y., Motomochi A., Tooyama I., Fujioka Y., Sakai N., Higaki S., Takada T.
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Journal Title
Toxicology in Vitro
Volume: 89
Pages: 105565-105565
DOI
Related Report
Peer Reviewed
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[Journal Article] Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory2022
Author(s)
Takei,Y., Amagase,Y., Iida,K.,Sagawa,T., Goto,A.,Kambayashi,R., Izumi-N,H., Matsumoto,A., Kawai,S., Sugiyama,A., Takada T., Hirasawa A.
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Journal Title
GeroScience
Volume: 44
Issue: 4
Pages: 2305-2318
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Global DNA Methylation in Cord Blood as a Biomarker for Prenatal Lead and Antimony Exposures2022
Author(s)
Okamoto, Y., Iwai-Shimada, M., Nakai K., Tatsuma, N., Mori, Y, Aoki, A, Kojima, N., Takada, T., Satoh, H., and Jinno, H.,
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Journal Title
Toxics
Volume: 10
Issue: 4
Pages: 157-157
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Germ cell-specific expression of Venus by Tol2-mediated transgenesis in endangered endemic cyprinid Honmoroko (Gnathopogon caerulescens)2021
Author(s)
Higaki S.*, Nishie T.*, Todo T., Teshima R., Kusumi K., Mitsumori R., Tooyama I., Fujioka Y., Kawasaki T., Sakai N., Takada T.
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Journal Title
J. Fish Biol
Volume: 99
Issue: 4
Pages: 1341-1347
DOI
Related Report
Peer Reviewed
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[Journal Article] Transcriptome analysis revealed bisphenol A and nonylphenol affect reproduction2019
Author(s)
Tanaka T., Ono Y.,Hikihara N., Yoshida A.,Yamada H.,Higaki S., Nishie T., Tooyama I., Iida K., Hirasawa A., Takada T.
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Journal Title
Reprod. Toxicol.
Volume: 88
Pages: 39-47
DOI
Related Report
Peer Reviewed
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