Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging.

IF 2 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Gynecological Endocrinology Pub Date : 2025-12-01 Epub Date: 2025-02-26 DOI:10.1080/09513590.2025.2471549

Hui Guo, Shu-Hong Pan, Jian Zhao, De-Xian Kong, Cai-Ping Geng, Sui-Bing Miao

{"title":"Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging.","authors":"Hui Guo, Shu-Hong Pan, Jian Zhao, De-Xian Kong, Cai-Ping Geng, Sui-Bing Miao","doi":"10.1080/09513590.2025.2471549","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2471549"},"PeriodicalIF":2.0000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecological Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09513590.2025.2471549","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/26 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

背景：方法：收集年轻/对照组和高龄/高龄产妇组（AMA）的人和小鼠GC，测定GC的衰老程度。在KGN细胞衰老模型中检验并验证了DNMT1-p53轴在卵巢衰老过程中GC衰老中的作用：结果：AMA组中SA-beta-gal阳性的GC明显增加，同时伴有p53-p21通路的激活，这在衰老小鼠的GC和H2O2诱导衰老的KGN细胞中也有发现。热序列甲基化分析显示，在衰老的 GCs 和 KGN 细胞中，p53 表达的增加与 P53 启动子 CpG 岛内 CpG 位点（-1031、-1019、-1012 和 -1008）平均甲基化水平的降低有关。我们进一步发现，DNA-甲基转移酶1（DNMT1）表达的减少是CpG位点甲基化水平降低的原因：结论：GCs 中 DNMT1 的减少以及 P53 启动子 CpG 岛内 CpG 位点的低甲基化与卵巢衰老有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gynecological Endocrinology 医学-妇产科学

CiteScore

4.40

自引率

5.00%

发文量

137

审稿时长

3-6 weeks

期刊介绍： Gynecological Endocrinology , the official journal of the International Society of Gynecological Endocrinology, covers all the experimental, clinical and therapeutic aspects of this ever more important discipline. It includes, amongst others, papers relating to the control and function of the different endocrine glands in females, the effects of reproductive events on the endocrine system, and the consequences of endocrine disorders on reproduction