2021 Fiscal Year Final Research Report
Approaches to understanding the pathogenesis of pregnancy-induced hypertension using an endometrial organoid model
| Project/Area Number |
19K09765
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 脱落膜化 / 妊娠高血圧症候群 |
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| Outline of Final Research Achievements |
We have generated an organoid-like culture model of human endometrium to clarify the importance of local progesterone metabolic mechanisms and the role of progesterone receptor membrane component factor 1 in decidualization. Down-regulation of progesterone receptor membrane component 1 expression during differentiation into syncytiotrophoblast cells, which constitute placental villi, promotes differentiation and cell fusion which contribute to the maintenance of pregnancy, Furthermore, dysregulation of the progesterone-associated factors may associate with the onset of HDP.
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| Free Research Field |
生殖内分泌学、薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
生体環境を模倣する子宮内膜オルガノイド培養系を利用し、子宮内膜における局所的なプロゲステロン代謝機構とプロゲステロン受容体膜構成因子1の役割を明らかとした。脱落膜化過程におけるこれらプロゲステロンシグナル関連因子の発現制御が、着床に向けた子宮内膜の機能的分化を促進し、さらに胎盤形成に関わる合胞体栄養膜細胞への分化・細胞融合を促進したことから、妊娠の成立・維持におけるプロゲステロンシグナル関連因子の発現制御機構の重要性が示唆された。子宮内膜・栄養膜の分化機構の異常と密接に関連するHDPの発症において本シグナル関連因子が治療ターゲットとなりうる可能性が推察された。
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