研究課題/領域番号 |
21K15010
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研究種目 |
若手研究
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配分区分 | 基金 |
審査区分 |
小区分42040:実験動物学関連
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研究機関 | 名古屋市立大学 |
研究代表者 |
シャウキ ホッサム 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70829738)
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研究期間 (年度) |
2021-04-01 – 2024-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2022年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
2021年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
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キーワード | reproductive aging / progesterone / Tcf23 |
研究開始時の研究の概要 |
Reproductive aging implies a sharp decline in female fertility and an increase in pregnancy complications with maternal age. The major characteristics of the reproductive aging are low birth rate/embryonic malformation caused by defective decidualization at early pregnancy, and the greater risk of operative delivery due to prolong gestational period at late pregnancy. In this study, we compare the difference of hormone levels and the gene expression profiles between young and aged pregnant female mice to develop a novel strategy to get healthy babies in aged women similar to the young.
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研究実績の概要 |
In 2022, we cleared reproductive phenotypes of Tcf23 knockout (KO) mice. The female KO mice showed no defects of decidualization of endometrium and the maintenance of pregnancy; however the myometrium of aged KO mice poorly responded to the oxytocin and other contraction stimuli. To understand the mechanism more deeply, RNA-seq analysis of KO myometrium was performed, and the results showed several contraction-related genes were downregulated in KO mice. In addition, based on the previous publication, there was an new possible protein to directly bind to Tcf23 and control the myometrium function. Tcf23 might negatively regulate the myometrium contraction by foming the heterodimer with the unkonwn protein and block it's function.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Two thirds of the project has been completed.
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今後の研究の推進方策 |
I am planing to find molecules to bind Tcf23 and control the myometrium function as well as the downstream targets of Tcf23, which causes the abnormal status during pregnancy. In 2023, the roles of Tcf23 and related signal transduction will be examined as a negative regulator of progesterone. The output of the current project will support maintaining suitable strategies of caring an aged woman during pregnancy, which is a burgeoning clinical problem.
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