| 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 |
Shawki Hossam 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 |
Completed (Fiscal Year 2023)
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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 | Aging / Uterus / Myometrium / TCF23 / 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 Final Research Achievements |
Women become less fertile and experience more pregnancy problems as they get older. This includes fewer births, birth defects, and a higher need for surgery during childbirth. Here, we studied older pregnant mice to understand how hormones and genes affect pregnancy. We found that older mice have normal estrogen but higher levels of progesterone. The altered levels of progesterone disrupt the necessary progesterone signaling for various pregnancy stages, such as the withdrawal of progesterone at late pregnancy, essential for triggering myometrial contraction genes. Moreover, aged uterine cells exhibit epigenetic alterations that do not respond to hormone-balancing strategies, necessitating alternative epigenetic resetting methods. We also identified a novel target protein related to labor initiation, TCF23, which is involved in obstructed labor in mice. TCF23 knockout mice revealed poor responsiveness of the myometrium to remodeling and contraction.
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| Academic Significance and Societal Importance of the Research Achievements |
研究は、マウスの生殖加齢に関する重要な洞察を提供し、特に妊娠と分娩時の合併症に焦点を当てます。目的は、脱落膜化や長期妊娠などの原因を最小限に抑えることです。若いおよび高齢マウスの妊娠中のホルモンおよび分子メカニズムを調査し、加齢雌性の主要な生理学的変化を明らかにします。さらに、若いが高齢の子宮筋層における遺伝子発現パターンと分娩の始まりを特定しました。新しい標的遺伝子が脱落膜化と分娩の開始に重要であることも明らかになりました。これらの発見は、加齢マウスで観察される子宮筋層の反応性の低下に対する治療介入の潜在的な標的を提供します。
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