Investigating methods to prevent obstetrics and gynecology diseases by regulating the contraction of the uterus through the circadian rhythm

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tokyo Medical University (2021-2022); Kanazawa University (2019-2020)
• Principal Investigator: Ono Masanori 東京医科大学, 医学部, 准教授 (70348712)
• Co-Investigator(Kenkyū-buntansha): 毎田 佳子 金沢大学, 保健学系, 教授 (20397219) ; 藤原 浩 金沢大学, 医学系, 教授 (30252456) ; 大黒 多希子 金沢大学, 学際科学実験センター, 教授 (30767249) ; 安藤 仁 金沢大学, 医学系, 教授 (50382875) ; 藤原 智子 京都ノートルダム女子大学, 現代人間学部, 教授 (60310744)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 概日リズム / 時計遺伝子 / 末梢時計 / 子宮 / 概日時計

Outline of Final Research Achievements

We verified that the mouse uterus exhibits circadian rhythmic expression of clock genes. Additionally, to examine the relation between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock. We found that time-restricted feeding regulates a circadian rhythm of the uterine clock that is synchronized throughout the uterine body. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation. A significant prevalence of gestational hypertension, which is assumed to be brought on by placental dysplasia in early pregnancy, was found in a cohort study of pregnant women who had menstruation pain at a young age.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、概日リズムの乱れと月経困難症、子宮筋腫、子宮内膜症、妊娠高血圧症候群などの産婦人科疾患との関係を明らかにするための研究を行った。また概日リズムの乱れによる新たな病態生理を提言するために、子宮特異的な時計遺伝子改変マウスを作出し解析した。加えてモデル動物のみならず、ヒト検体を用いた実験系、そしてコホート研究を基にした臨床研究を行い、多角的に概日リズムの乱れと産婦人科疾患の関連について解析した。本研究により、子宮における末梢時計機能が生殖機能に関わっていることが明らかとなった。少子化が極めて深刻な本邦において、生殖・周産期予後改善の観点から医学的意義は重要な成果と考える。