Elucidation of novel molecular mechanisms for maintenance of spermatogonial stem cells and gametogenesis in the testis
| Project/Area Number |
18H02643
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
櫻井 靖高 北里大学, 医学部, 助教 (50733101)
一戸 昌明 北里大学, 医学部, 講師 (80365163)
市原 正智 中部大学, 生命健康科学部, 教授 (00314013)
吉田 松生 基礎生物学研究所, 生殖細胞研究部門, 教授 (60294138)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 配偶子形成 / 精原幹細胞 / REV7 / コンディショナルノックアウトマウス / 精巣 / 生殖細胞 / マイクロアレイ解析 / 精子形成不全 / 遺伝子発現 / プロモーター解析 / 結合蛋白 / REV7コンディショナルノックアウトマウス / 精子形成 |
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| Outline of Final Research Achievements |
In the present study, we investigated the significance of REV7 in spermatogenesis. In consequence, we demonstrated a possibility that REV7 plays an important role in self-renewal of the spermatogonial stem cells. Induced deletion of REV7 in adult mice caused alterations of expression of genes involved in spermatogenesis in the testis. We identified various proteins interacting with REV7 using germ cell tumor cell lines, and we also found several candidates of transcription factors that control REV7 expression. In addition, using biopsy specimens of the testes in patients with male infertility, we immunohistochemically revealed that REV7 expression in the germ cells in seminiferous tubes was associated with severity of impairment in sperm maturation. These results indicate that REV7 is essential in adult spermatogenesis, and it is necessary to elucidate the functional mechanism of REV7 in spermatogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、生殖細胞維持・精子形成においてREV7が必須の蛋白であることが初めて明らかになったことから、精子形成過程をコントロールする新たな分子メカニズムを提唱することができる。それにより、生殖細胞研究に今までと異なった新しい視点を提案することができ、今後の生殖細胞研究の進展が期待できる。また、REV7の欠損が引き起こす病態を詳しく解析することにより、遺伝子発現異常による男性不妊症の発症機序の一端を解明できる可能性があり、将来的に精子形成不全、無精子症などの男性不妊症の原因解明、治療の開発に貢献することができる可能性がある。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] TRAP1 is a predictive biomarker of platinum-based adjuvant chemotherapy benefits in patients with resected lung adenocarcinoma2020
Author(s)
Kuchitsu Y, Nagashio R, Igawa S, Kusuhara S, Tsuchiya B, Ichinoe M, Satoh Y, Naoki K, Murakumo Y, Saegusa M, Sato Y.
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Journal Title
Biomedical Research
Volume: 41
Issue: 1
Pages: 53-65
DOI
NAID
ISSN
0388-6107, 1880-313X
Year and Date
2020-02-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inactivation of REV7 enhances chemosensitivity and overcomes acquired chemoresistance in testicular germ cell tumors.2020
Author(s)
Sakurai Y, Ichinoe M, Yoshida K, Nakazato Y, Saito S, Satoh M, Nakada N, Sanoyama I, Umezawa A, Numata Y, Shi-Xu J, Ichihara M, Takahashi M, Murakumo Y
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Journal Title
Cancer Lett.
Volume: 489
Pages: 100-110
DOI
Related Report
Peer Reviewed
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[Journal Article] Cytoskeleton-associated protein 4 is a novel serodiagnostic marker for lung cancer.2018
Author(s)
Yanagita Kengo, Nagashio Ryo, Jiang Shi-Xu, Kuchitsu Yuki, Hachimura Kazuo, Ichinoe Masaaki, Igawa Satoshi, Fukuda Eriko, Goshima Naoki, Satoh Yukitoshi, Murakumo Yoshiki, Saegusa Makoto, Sato Yuichi.
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Journal Title
American Journal of Pathology
Volume: 188
Issue: 6
Pages: 1328-1333
DOI
Related Report
Peer Reviewed / Open Access
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