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Study on the mechanism of feto-maternal communication via micro-RNA

Research Project

Project/Area Number 19K09821
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Miyasaka Naoyuki  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70313252)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNik-related kinase / 分娩遅延 / ノックアウトマウス / 絨毛合胞体細胞層 / 胎児胎盤系 / Nrk / マイクロRNA / 陣痛発来 / エクソソーム
Outline of Research at the Start

低出生体重児の原因は早産と胎児発育不全に大別されるが、分娩発来のメカニズム、胎児発育を規定する要因については不明な点が多い。近年母体血中を循環するマイクロRNA(miRNA)が、陣痛発来や胎児発育に関与している可能性が示唆されている。本研究では分娩時期異常や胎児発育異常を来す実験動物モデルおよびヒト臨床検体の解析により、早産および胎児発育不全と関連するmiRNAを抽出し、その由来、標的臓器、機能を解明するとともに、早期診断のためのバイオマーカーとしての有用性を明らかにする。

Outline of Final Research Achievements

We investigated the mechanism responsible for the delayed delivery in Nik-related kinase (Nrk)-knockout mice. By comparing the expressed genes in the term placenta between Nrk-knockout and control mice, we found that progestin and adipo Q receptor family member 9, and prolactin family members were upregulated and prostaglandin synthase cyclooxygenase 2 was down regulated in Nrk-knock out mice. Electron microscopic study showed that placental Golgi bodies in Nrk-knockout were significantly enlarged, which indicated secretion dysfunction of the placental products might be the cause of delayed delivery. Moreover, we found that insufficient progesterone reduction at term was the main reason for the delayed delivery in Nrk-knockout mice. In addition, we investigated Nrk expression in the human placenta in order to evaluate whether Nrk was associated with the post term pregnancy. It was revealed the Nrk was also expressed in syncytial trophoblasts in human placenta.

Academic Significance and Societal Importance of the Research Achievements

妊娠42週以降の過期妊娠は母児の周産期予後が極めて不良であるが、ヒトにおける陣痛発来のメカニズムは未だに解明されていない。Nrk-knockout胎仔を正常母体に移植したマウスにおいて高率に分娩遅延が発生し母児の死亡率が高いことから、胎仔もしくは胎盤から何らかのシグナルが母体に作用して陣痛が開始されていることが示唆される。本研究ではNrkが陣痛発来を抑制するプロゲステロン関連の遺伝子を増強し、陣痛発来を促進するプロスタグランジン関連遺伝子を抑制することで分娩遅延を来すことを初めて証明した。また、Nrkがヒト胎盤においても母体血と接触する合胞体絨毛細胞に発現していることを世界に先駆けて証明した。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] A possible function of <i>Nik-related kinase</i> in the labyrinth layer of delayed delivery mouse placentas2023

    • Author(s)
      Hiroshi Yomogita, Hikaru Ito, Kento Hashimoto, Akihiko Kudo, Toshiaki Fukushima, Tsutomu Endo, Yoshikazu Hirate, Yoshihiro Akimoto, Masayuki Komada, Yoshiakira Kanai, Naoyuki Miyasaka, Masami Kanai-Azuma
    • Journal Title

      Journal of Reproduction and Development

      Volume: 69 Issue: 1 Pages: 32-40

    • DOI

      10.1262/jrd.2022-120

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Review of Delayed Delivery Models and the Analysis Method in Mice.2022

    • Author(s)
      Hiroshi Yomogita, Naoyuki Miyasaka, Masami Kanai-Azuma
    • Journal Title

      J Dev Biol

      Volume: 10(巻) Issue: 2 Pages: 20-20

    • DOI

      10.3390/jdb10020020

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス、ヒト胎盤におけるNrk下流遺伝子群と分娩遅延の関連について2021

    • Author(s)
      蓬田裕、伊藤日加瑠、平手良和、宮坂尚幸、金井正美
    • Organizer
      日本分子生物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] マウス・ヒトにおけるNrk遺伝子発現の比較検討2020

    • Author(s)
      蓬田裕、伊藤日加瑠、平手良和、宮坂尚幸、金井正美
    • Organizer
      日本獣医学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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