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Genetic alteration from in-vitro culture environment in mammalian offspring born through in vitro fertilization

Research Project

Project/Area Number 19K09787
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 University

Principal Investigator

NAOKI KJI  東京医科大学, 医学部, 教授 (80169987)

Co-Investigator(Kenkyū-buntansha) 笹岡 俊邦  新潟大学, 脳研究所, 教授 (50222005)
阿久津 英憲  国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225)
山中 紋奈  東京医科大学, 医学部, 助教 (60838689)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsマウス / 体外受精 / オクタン酸 / インプリンティング / 体外培養 / 胎仔 / 体重
Outline of Research at the Start

ヒト体外受精(凍結胚移植)で児の出生体重が増加することが知られている。一方ほぼ全てのヒト体外受精培養液中に高濃度で含まれるオクタン酸は、マウス体外培養で産仔出生体重変化を来すことが報告されている。本研究ではマウス胚への培養時オクタン酸暴露モデルを用いて、胚盤胞までの初期胚培養環境(高濃度オクタン酸)が産仔(F1)・および産仔の子ども(F2)世代に与える遺伝学的影響を、1)産仔の発育・発達、2)遺伝子発現解析、3)遺伝子メチル化解析から解析する。

Outline of Final Research Achievements

The effect of octanoic acid (OA) in the embryo culture medium was investigated. Mouse embryos were cultured in KSOM culture medium containing0.5% w/v of recombinant human albumin, 400 mmM of N-acetyl tryptophan, and 0, 400, and 600 mmM of OA, respectively. The blastocyst development rates were 32/34 (94%), 28/36 (78%), and 28/40 (70%), respectively, significantly decreased with increasing OA concentration. After embryo transfer to pseudo-pregnant female mice, average birth weight of female pup were 1.08 ± 0.06 g, 1.15 ± 0.09 g, and 1.45 ± 0.05 g, tended to increase with increasing OA concentration (p = 0.05 in the 0μM group and 60μM group). However, in males, there was no difference in birth weight due to OA concentration, and there was no significant difference in weight up to 4 weeks after birth both in males and females. It was suggested that exposure to high concentrations of octanoic acid during embryo culture could increase birth weight in females.

Academic Significance and Societal Importance of the Research Achievements

ヒト体外受精由来出生(凍結胚移植由来)児は自然妊娠児に比較して出生体重が重いことが知られており、体外胚培養によって胚がうける影響についての関心は高いが、影響を来す因子やその遺伝子変化については詳しく解明されてない。ヒト体外受精培養液のほぼすべてに、生理的濃度の1000倍以上のオクタン酸(以下Octanoic Acid、以下OA)が添加されている。我々はOAがマウス胚にとりこまれ、エネルギー代謝に利用されていることを報告している。
本研究の成果は、OAがヒト体外培養中に胚に影響する可能性を示唆するとともに、その病因解明のモデル系を提供する可能性がある。

Report

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

    (3 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Mitochondrial replacement by genome transfer in human oocytes: Efficacy, concerns, and legality.2020

    • Author(s)
      Yamada M, Sato S, Ooka R, Akashi K, Nakamura A, Miyado K, Akutsu H, Tanaka M.
    • Journal Title

      Reprod Med Biol.

      Volume: 3:20(1) Issue: 1 Pages: 53-61

    • DOI

      10.1002/rmb2.12356

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes.2020

    • Author(s)
      Yamada M, Akashi K, Ooka R, Miyado K, Akutsu H.
    • Journal Title

      Int J Mol Sci.

      Volume: 16:21(16) Issue: 16 Pages: 5880-5880

    • DOI

      10.3390/ijms21165880

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳研究に必須な遺伝子改変マウスの系統保存に重要な培養条件の検討2021

    • Author(s)
      久慈直昭
    • Organizer
      2021年度脳研共同利用共同研究 笹岡合同セミナー
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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