Identification of functional abnormalities and differentiation mechanisms of spermatogonial stem cells in testicular dysgenesis syndrome.
| Project/Area Number |
18K09142
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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 |
Kamisawa Hideyuki 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00551277)
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| Co-Investigator(Kenkyū-buntansha) |
林 祐太郎 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40238134)
安井 孝周 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153)
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)
黒川 覚史 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50468253)
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)
西尾 英紀 名古屋市立大学, 医薬学総合研究院(医学), 助教 (10621063)
岩月 正一郎 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70595397)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 精子幹細胞 / 少子化問題 / 停留精巣 / 精巣形成不全症候群 / 精巣癌 / 尿道下裂 / 男性不妊症 |
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| Outline of Final Research Achievements |
The treatment and elucidation of the pathogenesis of Testicular Dysgenesis Syndrome (TDS), represented by undescended testes and hypospadias, is an important issue in Japan, where the birthrate is declining and the number of children is urgently needed to be addressed.
In this study, we clarified the decrease in sperm stem cell function in TDS testes and succeeded in identifying UFF1 and KDM5A as causative genes. We also showed that high temperature in the testes causes abnormal gene expression in spermatogonial stem cells, leading to impaired spermatogenesis. Furthermore, we identified CLDN11 as a gene responsible for the dysfunction of Sertoli cells, which are the supporting cells of spermatogonial stem cells, and their component blood-testis barrier in the TDS testis.
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| Academic Significance and Societal Importance of the Research Achievements |
精巣形成不全症候群（Testicular Dysgenesis Syndrome；TDS）は胎生期の性成熟過程において遺伝的要因・環境的要因により男性生殖機能障害が引き起こされる疾患群のことであり、停留精巣、精子減少症、精巣癌などが代表的疾患である。TDS患者では造精機能障害による男性不妊症が引き起こされるため、少子化問題が喫緊の課題である我が国においてその対策は急務である。本研究は生後早期からの精子幹細胞（SSC）機能低下を示すとともに、その原因遺伝子群を同定し、停留精巣の早期手術や精索静脈瘤手術が造精機能障害を改善させることを科学的に明らかにし、その有用性の社会的啓蒙に有意義と考えられる。
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Report
(6 results)
Research Products
(47 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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[Presentation] Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model2020
Author(s)
Kato Taiki, Mizuno Kentaro, Nishio Hidenori, Moritoki Yoshinobu, Kamisawa Hideyuki, Kurokawa Satoshi, Nakane Akihiro, Maruyama Tetsuji, Ando Ryosuke, Hayashi Yutaro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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