Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging
Background The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature ovarian failure have been extensively examined, the association between GC senescence and ovarian aging remains to be clarified.Methods Human and mouse GCs from young/control and old/advanced matern...
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Taylor & Francis Group
2025-12-01
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| Series: | Gynecological Endocrinology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09513590.2025.2471549 |
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| author | Hui Guo Shu-Hong Pan Jian Zhao De-Xian Kong Cai-Ping Geng Sui-Bing Miao |
| author_facet | Hui Guo Shu-Hong Pan Jian Zhao De-Xian Kong Cai-Ping Geng Sui-Bing Miao |
| author_sort | Hui Guo |
| collection | DOAJ |
| description | Background The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature ovarian failure have been extensively examined, the association between GC senescence and ovarian aging remains to be clarified.Methods Human and mouse GCs from young/control and old/advanced maternal age (AMA) groups were collected, and GC senescence was determined. The role of the DNMT1–p53 axis in GC senescence during ovarian aging was examined and validated in a KGN cell senescence model.Results SA-beta-gal-positive GCs were significantly increased in the AMA group, accompanied by activation of the p53–p21 pathway, which was also found in GCs from aged mice and H2O2-induced senescent KGN cells. Pyrosequencing methylation analysis revealed that increased expression of p53 was associated with decreased average methylation levels of CpG sites (−1031, −1019, −1012 and −1008) within the P53 promoter CpG island in senescenct GCs and KGN cells. We further found that decreased DNA-methyltransferase 1 (DNMT1) expression was responsible for the reduced methylation levels of the CpG sites.Conclusion Decreased DNMT1 with hypomethylation of the CpG sites within the P53 promoter CpG island in GCs is involved in ovarian aging. |
| format | Article |
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| issn | 0951-3590 1473-0766 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Gynecological Endocrinology |
| spelling | doaj-art-a859e13a511a41049a48bef93991be8a2025-08-20T01:56:57ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662025-12-0141110.1080/09513590.2025.2471549Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian agingHui Guo0Shu-Hong Pan1Jian Zhao2De-Xian Kong3Cai-Ping Geng4Sui-Bing Miao5Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Maternal and Fetal Medicine, Institute of Reproductive Medicine of Shijiazhuang, the Fourth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Gynecology, the People’s Hospital of Shijiazhuang, Shijiazhuang, Hebei, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Maternal and Fetal Medicine, Institute of Reproductive Medicine of Shijiazhuang, the Fourth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Maternal and Fetal Medicine, Institute of Reproductive Medicine of Shijiazhuang, the Fourth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, ChinaBackground The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature ovarian failure have been extensively examined, the association between GC senescence and ovarian aging remains to be clarified.Methods Human and mouse GCs from young/control and old/advanced maternal age (AMA) groups were collected, and GC senescence was determined. The role of the DNMT1–p53 axis in GC senescence during ovarian aging was examined and validated in a KGN cell senescence model.Results SA-beta-gal-positive GCs were significantly increased in the AMA group, accompanied by activation of the p53–p21 pathway, which was also found in GCs from aged mice and H2O2-induced senescent KGN cells. Pyrosequencing methylation analysis revealed that increased expression of p53 was associated with decreased average methylation levels of CpG sites (−1031, −1019, −1012 and −1008) within the P53 promoter CpG island in senescenct GCs and KGN cells. We further found that decreased DNA-methyltransferase 1 (DNMT1) expression was responsible for the reduced methylation levels of the CpG sites.Conclusion Decreased DNMT1 with hypomethylation of the CpG sites within the P53 promoter CpG island in GCs is involved in ovarian aging.https://www.tandfonline.com/doi/10.1080/09513590.2025.2471549Senescencegranulosa cellovarian agingmethylationDNA-methyltransferase 1 |
| spellingShingle | Hui Guo Shu-Hong Pan Jian Zhao De-Xian Kong Cai-Ping Geng Sui-Bing Miao Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging Gynecological Endocrinology Senescence granulosa cell ovarian aging methylation DNA-methyltransferase 1 |
| title | Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| title_full | Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| title_fullStr | Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| title_full_unstemmed | Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| title_short | Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| title_sort | reduced dnmt1 expression associated with tp53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging |
| topic | Senescence granulosa cell ovarian aging methylation DNA-methyltransferase 1 |
| url | https://www.tandfonline.com/doi/10.1080/09513590.2025.2471549 |
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