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Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2

Author

Listed:
  • Hong-Yan Guo

    (Qingdao Agricultural University)

  • Shou-Bin Tang

    (Qingdao Agricultural University
    Nanjing Medical University)

  • Li-Jun Li

    (Qingdao Agricultural University)

  • Jing Lin

    (Qingdao Agricultural University
    Qingdao Agricultural University)

  • Ting-Ting Zhang

    (Henan Provincial People’s Hospital)

  • Shuo Chao

    (Qingdao Agricultural University)

  • Xiao-Wen Jin

    (Qingdao Agricultural University)

  • Kui-Peng Xu

    (Qingdao Agricultural University)

  • Xiao-Feng Su

    (Qingdao Agricultural University)

  • Shen Yin

    (Qingdao Agricultural University)

  • Ming-Hui Zhao

    (Qingdao Agricultural University)

  • Gui-An Huang

    (Qingdao Agricultural University)

  • Li-Jia Yang

    (Qingdao Agricultural University)

  • Wei Shen

    (Qingdao Agricultural University)

  • Lei Zhang

    (Tsinghua University)

  • Cui-Lian Zhang

    (Henan Provincial People’s Hospital)

  • Qing-Yuan Sun

    (Guangdong Second Provincial General Hospital
    Jinan University)

  • Zhao-Jia Ge

    (Qingdao Agricultural University)

Abstract

Gestational diabetes mellitus (GDM), a common pregnancy disease, has long-term negative effects on offspring health. Epigenetic changes may have important contributions to that, but the underlying mechanisms are not well understood. Here, we report the influence of GDM on DNA methylation of offspring (GDF1) oocytes and the possible mechanisms. Our results show that GDM induces genomic hyper-methylation of offspring oocytes, and at least a part of the altered methylation is inherited by F2 oocytes, which may be a reason for the inheritance of metabolic disorders. We further find that GDM exposure increases the expression of Ezh2 in oocytes. Ezh2 regulates DNA methylation via DNMT1, and Ezh2 knockdown reduces the genomic methylation level of GDF1 oocytes. These results suggest that GDM may induce oocyte genomic hyper-methylation of offspring via enhancing the Ezh2 expression recruiting more DNMT1 into nucleus.

Suggested Citation

  • Hong-Yan Guo & Shou-Bin Tang & Li-Jun Li & Jing Lin & Ting-Ting Zhang & Shuo Chao & Xiao-Wen Jin & Kui-Peng Xu & Xiao-Feng Su & Shen Yin & Ming-Hui Zhao & Gui-An Huang & Li-Jia Yang & Wei Shen & Lei Z, 2025. "Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55499-x
    DOI: 10.1038/s41467-024-55499-x
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    References listed on IDEAS

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