The elucidation of the mechanism of Kdm5a, the histone-modifying enzyme, aimed at epigenetic drug discovery for testicular dysfunction
| Project/Area Number |
18K09202
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Nishio Hidenori 名古屋市立大学, 医薬学総合研究院(医学), 助教 (10621063)
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| Co-Investigator(Kenkyū-buntansha) |
安井 孝周 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153)
林 祐太郎 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40238134)
水野 健太郎 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70448710)
神沢 英幸 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00551277)
守時 良演 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50595395)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 造精機能障害 / ヒストン修飾 / エピジェネティクス / エピゲノム / 精子形成障害 / 停留精巣 / 精子幹細胞 |
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| Outline of Final Research Achievements |
Mouse spermatogonial GC-1 cells were transfected with Kdm5a expression vectors. We performed a microarray analysis to clarify the underlying regulatory mechanisms of Kdm5a overexpression. Moreover, we identified the pathways that were altered by Kdm5a expressions using the IPA (Ingenuity Pathways Analysis) software. The IPA showed a Kdm5a-activated pathway of the “Actin Cytoskeleton Signaling,” which included Ret. Because RET receptors colocalize with Gfra1 in the spermatogonial stem cells and Gdnf- signaling via the RET-tyrosine-kinase/Gfra1 receptor complex is required for spermatogonial stem cell self-renewal, it is suggested that Kdm5a regulates the differentiation from gonocytes to spermatogonia via activation of the “Actin Cytoskeleton Signaling” pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で、造精機能障害モデルである停留精巣ラットで発現亢進するKdm5a遺伝子が高発現することによって、精子形成に関連する遺伝子群の発現異常が生じることが明らかとなった。男性不妊症における造精機能障害の原因は明らかでないため、造精機能障害を回復する根本的な治療法は存在しないが、この精子形成に関連する遺伝子群に対する治療薬の開発により、今後の男性不妊症に対する新規治療薬の開発が期待される。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Mullerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism2021
Author(s)
Kato T, Mizuno K, Matsumoto D, Nishio H, Nakane A, Kurokawa S, Kamisawa H, Maruyama T, Iwatsuki S, Umemoto Y, Yasui T, Hayashi Y
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Journal Title
J Urology
Volume: 207
Issue: 3
Pages: 701-709
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Robot-Assisted Radical Cystectomy for Pediatric Bladder Rhabdomyosarcoma.2020
Author(s)
Nishio H, Mizuno K, Kawase K, Kato T, Kamisawa H, Kurokawa S, Nakane A, Ando R, Maruyama T, Yasui T, Hayashi Y.
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Journal Title
J Endourol Case Rep.
Volume: 6
Issue: 4
Pages: 461-464
DOI
Related Report
Peer Reviewed
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