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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

    as
    1. Ryan Lister & Mattia Pelizzola & Robert H. Dowen & R. David Hawkins & Gary Hon & Julian Tonti-Filippini & Joseph R. Nery & Leonard Lee & Zhen Ye & Que-Minh Ngo & Lee Edsall & Jessica Antosiewicz-Bourg, 2009. "Human DNA methylomes at base resolution show widespread epigenomic differences," Nature, Nature, vol. 462(7271), pages 315-322, November.
    2. Yingfeng Li & Zhuqiang Zhang & Jiayu Chen & Wenqiang Liu & Weiyi Lai & Baodong Liu & Xiang Li & Liping Liu & Shaohua Xu & Qiang Dong & Mingzhu Wang & Xiaoya Duan & Jiajun Tan & Yong Zheng & Pumin Zhan, 2018. "Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1," Nature, Nature, vol. 564(7734), pages 136-140, December.
    3. Tie-Gang Meng & Qian Zhou & Xue-Shan Ma & Xiao-Yu Liu & Qing-Ren Meng & Xian-Ju Huang & Hong-Lin Liu & Wen-Long Lei & Zheng-Hui Zhao & Ying-Chun Ouyang & Yi Hou & Heide Schatten & Xiang-Hong Ou & Zhen, 2020. "PRC2 and EHMT1 regulate H3K27me2 and H3K27me3 establishment across the zygote genome," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    4. Emmanuelle Viré & Carmen Brenner & Rachel Deplus & Loïc Blanchon & Mario Fraga & Céline Didelot & Lluis Morey & Aleyde Van Eynde & David Bernard & Jean-Marie Vanderwinden & Mathieu Bollen & Manel Este, 2006. "The Polycomb group protein EZH2 directly controls DNA methylation," Nature, Nature, vol. 439(7078), pages 871-874, February.
    5. Azusa Inoue & Lan Jiang & Falong Lu & Tsukasa Suzuki & Yi Zhang, 2017. "Maternal H3K27me3 controls DNA methylation-independent imprinting," Nature, Nature, vol. 547(7664), pages 419-424, July.
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