Establishment of recovery spermatogenesis after chemotherapy due to the microenvironment modulation in seminiferous tubule
| Project/Area Number |
17591670
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOH Eitetsu Kanazawa University, Graduate School of Medicine, Associate Professor (90283134)
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| Co-Investigator(Kenkyū-buntansha) |
NAMIKI Mikio Kanazawa University, Graduate School of Medicine, Professor (70155985)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | spermatogenesis / meiosis / alternative splicing / DNA / homologuous chromosome / DMC1 / プロテオーム / 無精子症 / 2次元電気泳動 / ブスルファン |
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| Research Abstract |
As a result of having retrieving genetic information from NCBI, a gene which was damaged selectively due to the various anti-cancer agents has been selected. Moreover recovery-related proteins after treating using anti-cancer agents were also associated with the genes during expressing in the meiotic stage. These candidate genes contributed to spermatogenesis and were naive to various anti-cancer agents depended on their dose. Generally speaking, the most important process of meiotic stage is accurate distribution of homologous chromosomes. It is assumed that the homologous recombination between chromosomes occurred initially in a transient DNA double-strand break (DSB) in the beginning to meiotic stage. In the cross reaction between homologous strands, the proteins such as Rad51 or Rad52, Rad54, Rad55, Rad57, DMC1, Rpa1 play a central role in a eukaryote. Specially, it is reported that RAD51 has not replaced the function of DMC1 (GenBank, NM_007068) in meiotic stage according to the knockout mouse. The transcripts of DMC1 are particularly specific in meiotic stage and enable to recognize only homogenous strands.
Our study revealed that the transcripts of DMC1 were existed three products derived from alternative splicing. Clinically these transcripts had a various number in the idiopathic male infertility. According to analyzing the clinical samples, it was suggested that the number of the isoforms leaded to modify a motif and domain of the DMC1, and was thought to be induced apoptosis of spermatid. These genetic splicing variants contributed to meiotic control and clarified to affect the possibility of the spermatogenesis. Our study showed that one mechanism of spermatogenesis arrests was associated with the dysfunction of early stage during meiosis due to isofoms derived from domain specific proteins.
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Report
(3 results)
Research Products
(7 results)
