| Project/Area Number |
18591812
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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 |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
UCHIDA Hiroshi Keio University, School of Medicine, Instructor (90286534)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Tetsuo Keio University, School of Medicine, Assistant Professor (10209702)
YOSHIMURA Yasunori Keio University, School of Medicine, Professor (10129736)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,650,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | histone deacetylase inhibitor(HDACI) / glycodelin / implantation / endometrial epithelial cells / ヒストン脱アセチル化酸素阻害剤 / 子宮内膜線上皮 / 生殖医学 / 細胞運動 |
|---|
| Research Abstract |
Major part of molecular mechanism(s) of human implantation still remains unclear. Human uterine endometrium repeats breakdown, proliferation and differentiation for preparation of pregnancy in reproductive menstrual cycle. We have reported that histone deacetylase inhibitors (HDACI)can differentiate human endometrial epithelial and stromal cells without assistance by ovarian steroid hormones. To develop new strategy of treatment for fertile women, we analyzed whether HDACI can affect not only differentiation but also proliferation, motility and adhesion of endometrial epithelial cells during implantation.
In this study, we demonstrated the following phenomenon using in vitro model by model of human endometrial epithelial cells (Ishikawa cells) and embryonal cells (JAR cells).
By treatment of ovarian steroid hormones (17beta-estradol + progesterone) or HDACI
1. Ishikawa cell proliferation was down-regulated by cell-cycle arrest at G1/S check point or induced cell apoptosis.
2. Ishikawa cell motility was up-regulated in both single and collective cell migration assay.
3. Adhesion between Ishikawa cells and JAR spheroids were significantly enhanced.
Moreover, these results were
4. showed in a HDACI-dose dependent manner.
5. required for glycodelin induction.
Taken together, glycodelin induced by ovarian steroid hormones or HDACI can help for implantation rate through positive effect to differentiation, proliferation, motility, and adhesion. It is suggested that HDACI have a potential as a implantation-assisted reagent instead of hormonal reagents for fertile women.
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