Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55499-x |
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| author | 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 Zhang Cui-Lian Zhang Qing-Yuan Sun Zhao-Jia Ge |
| author_facet | 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 Zhang Cui-Lian Zhang Qing-Yuan Sun Zhao-Jia Ge |
| author_sort | Hong-Yan Guo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eb0ac2913ded4d51a8bf94fe3ed449e5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-eb0ac2913ded4d51a8bf94fe3ed449e52025-01-05T12:40:49ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55499-xGestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2Hong-Yan Guo0Shou-Bin Tang1Li-Jun Li2Jing Lin3Ting-Ting Zhang4Shuo Chao5Xiao-Wen Jin6Kui-Peng Xu7Xiao-Feng Su8Shen Yin9Ming-Hui Zhao10Gui-An Huang11Li-Jia Yang12Wei Shen13Lei Zhang14Cui-Lian Zhang15Qing-Yuan Sun16Zhao-Jia Ge17College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityReproductive Medicine Center, People’s Hospital of Zhengzhou University, Henan Provincial People’s HospitalCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Horticulture, Qingdao Agricultural UniversityCollege of Horticulture, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityDepartment of Obstetrics and Gynecology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua UniversityReproductive Medicine Center, People’s Hospital of Zhengzhou University, Henan Provincial People’s HospitalGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health and Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General HospitalCollege of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55499-x |
| spellingShingle | 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 Zhang Cui-Lian Zhang Qing-Yuan Sun Zhao-Jia Ge Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 Nature Communications |
| title | Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 |
| title_full | Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 |
| title_fullStr | Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 |
| title_full_unstemmed | Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 |
| title_short | Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2 |
| title_sort | gestational diabetes mellitus causes genome hyper methylation of oocyte via increased ezh2 |
| url | https://doi.org/10.1038/s41467-024-55499-x |
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