Project/Area Number |
21H02387
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Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 42040:Laboratory animal science-related
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Kanai Masami 東京医科歯科大学, 統合研究機構, 教授 (70321883)
|
Co-Investigator(Kenkyū-buntansha) |
伊藤 日加瑠 香川大学, 医学部, 准教授 (50587392)
|
Project Period (FY) |
2021-04-01 – 2024-03-31
|
Project Status |
Completed (Fiscal Year 2023)
|
Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
|
Keywords | 胎盤 / NRK / 分娩遅延 / 早産 / Nrk / 分娩 |
Outline of Research at the Start |
本申請では、Nrk KOマウス表現系を手掛かりに、正常な妊娠維持から分娩発来への切り替え調整機構を解明する。即ち、マウスとヒト胎盤の NRK 機能を比較することで、妊娠から分娩へのスイッチング因子を探索し母体環境に焦点を当てた研究を展開する。具体的には、Nrk下位分娩発来関連因子の同定、実際のヒト胎盤における定量化 (早産、正常出産、出産遅延の比較)、上記で同定した候補因子の抑制剤などを用いることでNrk 欠損個体の分娩遅延に対して、治療介入実験を実施しpathwayを確定する。
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Outline of Final Research Achievements |
The morphology of the placenta varies significantly among animal species. Primates, including humans, and rodents such as mice possess a hemomonochorial placenta, which has evolved similarly. In these placentas, the syncytiotrophoblast cells, which are in contact with maternal blood, are specialized for barrier functions and selective material exchange. The KO mice for the Nrk (NIK-related kinase) gene, which we originally isolated, exhibit placental hypertrophy and delayed parturition. From the phenotypes and RNA-seq analysis of these Nrk KO mice, we revealed that parturition is delayed because the rapid decline in maternal P4 (progesterone) levels typically observed at the onset of labor does not occur in Nrk KO individuals. Additionally, by investigating the candidate downstream genes of Nrk, we explored the switch mechanisms for signaling the transition from normal pregnancy to the onset of labor.
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Academic Significance and Societal Importance of the Research Achievements |
NRK KOによって分娩遅延が引き起こされる。本研究から、マウス胎盤がヒト胎盤の疾患モデルとしてカウンターパートであること、NRKが分娩誘導因子である可能性を示す結果が得られた。今後、マウスNRKとその下位因子と、ヒト早産の共通因子を、in silicoと病理切片を用いて更に検索することで、将来、早産の原因探索が可能となり、治療につながる可能性が示唆された。
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