Cellular level analysis of an embryo implantation process by means of uterine epithelium replacement
Project/Area Number |
17K07133
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Laboratory animal science
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | マウス / 子宮内膜 / TRECK法 / ジフテリア毒素 / 細胞移植 / in vivo エレクトロポレーション / 遺伝子導入 / 細胞置換 / 子宮内膜上皮細胞 / 幹細胞 / 脱細胞化組織 / CRISPR/Cas9 / 着床 / 実験動物学 / 遺伝学 / 疾患モデル |
Outline of Final Research Achievements |
Embryo implantation is an essential event in mammalian development. It occurs only when the uterus is in a receptive window. Molecular mechanisms that regulate the transition of the receptive window remains largely unknown. In this study, we aimed to develop new tools that facilitate analyses of implantation-related molecules. The first tool is a uterine epithelial (UE) cell replacement. The UE cells of a host mouse are eliminated by the toxin receptor-mediated conditional cell knockout system, and transplanted UE cells from a donor mouse with different genetic modification regenerate the UE, resulting in UE cell replacement with different genetic property from the host. The second tool is an in vivo gene delivery system by electroporation that allows for the UE cell specific genetic modifications. These newly developed tools are expected to facilitate study of implantation related genes and may improve the reliability of assisted reproductive technology.
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果である子宮上皮再生システムとin vivoエレクトロポレーションを活用することで、これまで解析手段がなかったために機能解明が進んでいなかった遺伝子の解析を進めることができ、着床の分子基盤の包括的理解を大きく前進させることができる。不妊治療として実施される体外受精(IVF)において、着床の失敗は治療が不成功に終わる原因の3分の1を占めており、この原因としてIVF後の胚移植のタイミングと子宮の受容期に入るタイミングとのズレが考えられている。子宮の胚受容についての理解が進み、子宮の受け入れ態勢をコントロールできるようになれば、不妊治療の成績の向上につながることが期待される。
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Report
(4 results)
Research Products
(11 results)