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2023 Fiscal Year Final Research Report

Progesterone fluctuated signals in females induced by reproductive aging

Research Project

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Project/Area Number 21K15010
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionNagoya City University

Principal Investigator

Shawki Hossam  名古屋市立大学, 医薬学総合研究院(医学), 助教 (70829738)

Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsAging / Uterus / Myometrium / TCF23
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.

Free Research Field

reproduction and development

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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Published: 2025-01-30  

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