Work

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

Year: 2025

Type: article

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.

Source: Gynecological Endocrinology

DOI: 10.1080/09513590.2025.2471549

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

Institutions: Hebei Medical University, Fourth Hospital of Hebei Medical University, First Hospital of Shijiazhuang

Language: English

Topic: Reproductive Biology and Fertility

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Natural Science Foundation of Hebei Province