TET3欠乏症による母性グルコース不耐性の遺伝

Bin Chen^1,2,3, Ya-Rui Du³, Hong Zhu^4,5

¹Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Nature

|May 18, 2022

まとめ

母親の妊娠中の高血糖症は,子孫を増やすことができます.

科学分野:

生殖生物学
内分泌学
エピジェネティクス

背景:

糖尿病は生殖年齢の多くの女性に影響します.
妊娠中の糖尿病は子孫の健康に長期的な影響を及ぼします
妊娠中の糖尿病が子孫の成人期疾患リスクに与える影響は十分に研究されていない.

研究の目的:

妊娠中の糖尿病と子孫のグルコース不耐症の関連を調べる
この母体効果を媒介する TET3 酸化酵素の役割を調べる.
潜在的妊娠前の介入を特定する

主な方法:

ハイパーグリセミアのマウスモデル (HGマウス) とヒトサンプルを使用した.
卵細胞におけるTET3ダイオキシゲナーゼ表現の評価
インスリン分泌遺伝子のDNAメチル化パターンを分析した.
子孫におけるグルコース・ホメオスタシスとエピジェネティックマーカーの検査

主要な成果:

HGマウスと糖尿病患者の卵細胞におけるTET3発現の減少
卵細胞TET3欠乏症は,父性のインスリン遺伝子 (例えば,Gck) の高メチル化につながる.
このエピジェネティックの変化は持続し,血糖の恒常性障害と子孫におけるインスリン分泌の欠陥を引き起こします.
ネズミにおける母性 Tet3 削除はこれらの効果を再現し,外因性 Tet3 mRNAはそれらを改善します.

結論:

妊娠中の高血糖症は,卵細胞発達の過程でTET3不全によって,子孫にグルコース不耐性を引き起こす.
このエピジェネティックメカニズムは,直接的な卵細胞の乱れではなく,母子の効果の根底にある.
母親の健康を狙った妊娠前の介入は子孫の代謝健康を守ることができます

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