精子の tsRNA は,代々の代謝障害の遺伝に寄与する

Qi Chen¹, Menghong Yan², Zhonghong Cao³

¹State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89512 USA.

Science (New York, N.Y.)

|January 2, 2016

まとめ

父の高脂肪食は精子 tsRNA を変化させ,子孫に代謝障害を引き起こします. これらの精子から派生した小さなRNAは代謝疾患の世代間伝播を媒介する表遺伝因子として作用する.

科学分野:

エピジェネティクス
生殖生物学
代謝障害

背景:

父親の食事は子孫の代謝健康に影響しますが,その背後にあるメカニズムは不明です.
ダイエットによる代謝障害は世代を超えて伝染する可能性があります

研究の目的:

子孫の代謝に対する父親の食事効果を媒介する精子の小RNAの役割を調査する.
代間代謝疾患の伝播に関与する特定の精子小RNAを特定する.

主な方法:

高脂肪食 (HFD) を摂取した父親のマウスモデルを使用した.
精子転送RNA由来小RNA (tsRNAs) の発現と改変プロファイルを分析した.
HFDのオスから正常な卵胞に精子 tsRNA 分子を注入した.
F1の子孫と初期胚における代謝パラメータと遺伝子発現の評価

主要な成果:

精子 tsRNA のサブセット (5' tRNA ハーフ,30- 34 nt) は,HFD の男性において変化したプロファイルを示した.
これらの tsRNAsの注射はF1の子孫に代謝障害を誘発した.
代謝経路における遺伝子発現の変化は,初期の胚とF1の子島で観察されました.
効果はCpG部位でのDNAメチル化変化とは無関係でした.

結論:

精子 tsRNA は,父親の食事による代謝障害の主要な媒介者である.
精子 tsRNA は,世代間の代謝遺伝子の父性表遺伝因子として機能する.
父のtsRNAを標的とした食事の介入は,代謝性疾患の伝染を防ぐことができます.

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