| Project/Area Number |
21K15010
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
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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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | reproductive aging / progesterone / Tcf23 |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Two thirds of the project has been completed.
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| Strategy for Future Research Activity |
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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