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Elucidation of the molecular mechanism of epigenomic changes caused by intermittent hypoxia during pregnancy and construction of a foundation for medical applications

Research Project

Project/Area Number 20H03895
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Ono Takashi  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30221857)

Co-Investigator(Kenkyū-buntansha) 細道 純  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00420258)
宮崎 泰成  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30396999)
宮坂 尚幸  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70313252)
財津 崇  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (80611508)
下澤 達雄  国際医療福祉大学, 医学部, 主任教授 (90231365)
森丘 千夏子  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座助教 (50796191)
滝 敦子  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (20614481)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords閉塞性睡眠時無呼吸症 / 妊娠女性 / 胎児 / 出生児 / DOHAD仮説 / 間欠的低酸素 / 間欠的低酸素状態 / 妊娠 / 動物モデル / 睡眠時無呼吸症候群 / 小児 / エピゲノム
Outline of Research at the Start

妊娠期における閉塞性睡眠時無呼吸症(OSA)は、胎児を間欠的低酸素(IH)に曝露し、出生後に成長遅延・神経発達障害・内分泌代謝異常などの全身病態をもたらす。この一因として、中枢や末梢の細胞・組織におけるDNA変化(エピゲノム変化)が推測されている。しかし、妊娠母体の睡眠呼吸障害と、出生後における胎児の中枢および成長発育障害を結ぶエピゲノム変化の関与について、未だほとんど解明されていない。そこで本研究は、OSA母子を対象とした疫学調査ならびに疾患動物モデルを用いた基礎研究の両面から、胎児期のIH曝露がエピゲノム変化を介して中枢および末梢の生後発達障害を惹起する分子機構を解明する。

Outline of Final Research Achievements

Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. We aimed to clarify the effects of IH in both pregnant patients and rats on the growth and develeopment of infants and adolescent offspring rats.
Clinical study suggested that higher BMI as a major risk factor for OSA among Japanese pregnant women. In addition, maternal OSA during pregnancy negatively influences birth weight and postnatal growth of the offspring.
Animal model study suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

Academic Significance and Societal Importance of the Research Achievements

これまで認識されていなかった妊娠期の睡眠呼吸障害が、次世代に成長発育障害をもたらす分子基盤の解明を国内外にて初めて行うことにより、妊娠期OSAのスクリーニングの重要性を啓発し、先制医療基盤構築の契機となり、巨視的には医療費の削減と「すべての人に健康と福祉を」という持続可能な開発目標(SDGs)に沿った健康長寿社会を実現する波及効果が期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (5 results)

All 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] チュラロンコン大学(タイ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia2023

    • Author(s)
      Wongkitikamjorn Wirongrong、Wada Eiji、Hosomichi Jun、Maeda Hideyuki、Satrawaha Sirichom、Hong Haixin、Yoshida Ken-ichi、Ono Takashi、Hayashi Yukiko K.
    • Journal Title

      Frontiers in Physiology

      Volume: 14 Pages: 1-14

    • DOI

      10.3389/fphys.2023.1067683

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Characteristics of obstructive sleep apnea among pregnant Japanese women and birth outcomes of offspring2023

    • Author(s)
      Takumi Suzuki, Jun Hosomichi, Naoyuki Miyasaka, Yasunari Miyazaki, Atsuko Taki, Takashi Zaitsu, Manaka Moro, Chikako Morioka, Noriko Sato, Takashi Ono
    • Organizer
      SLEEP 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日本人妊婦の閉塞性睡眠時無呼吸症の病態と出生児への影響について2023

    • Author(s)
      鈴木拓望1)、細道純1)、宮坂尚幸2)、宮崎泰成3)、滝敦子4)、財津崇5)、毛呂愛香1)、森丘千夏子4)、佐藤憲子6)、小野卓史
    • Organizer
      第47回日本女性栄養・代謝学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠期の間欠的低酸素曝露が仔ラットの下顎骨の出生後成長に与える影響について2022

    • Author(s)
      鈴木拓望、細道純、前田秀将、石田雄之、臼見莉沙、毛呂愛香、小野卓史
    • Organizer
      第81回日本矯正歯科学会学術大会
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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