Related Experiment Video

Updated: May 25, 2025

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
12:25

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome

Published on: February 24, 2023

776

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

Hui Guo1, Shu-Hong Pan2, Jian Zhao3

  • 1Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
|February 26, 2025
PubMed
Abstract

Insights

Granulosa cell (GC) senescence, marked by decreased DNA-methyltransferase 1 (DNMT1) and reduced P53 promoter methylation, is linked to ovarian aging. This finding clarifies the role of GC senescence in the aging process.

Area of Science:

  • Reproductive biology
  • Cellular senescence
  • Epigenetics

Background:

  • Granulosa cell (GC) senescence is implicated in premature ovarian insufficiency.
  • The specific role of GC senescence in general ovarian aging requires further clarification.

Purpose of the Study:

  • To investigate the association between granulosa cell senescence and ovarian aging.
  • To explore the involvement of the DNMT1-p53 axis in GC senescence during ovarian aging.

Main Methods:

  • Collected human and mouse granulosa cells (GCs) from young and advanced maternal age (AMA) groups.
  • Assessed GC senescence and validated the DNMT1-p53 axis in a KGN cell senescence model.
  • Utilized pyrosequencing for methylation analysis of the P53 promoter.

Main Results:

  • Advanced maternal age (AMA) showed increased SA-beta-gal-positive GCs and activated p53-p21 pathway.
  • Increased p53 expression correlated with decreased P53 promoter methylation in senescent GCs.
  • Reduced DNA-methyltransferase 1 (DNMT1) expression was identified as the cause of decreased methylation.

Conclusions:

  • Decreased DNMT1 and hypomethylation of the P53 promoter CpG island in GCs contribute to ovarian aging.
  • The DNMT1-p53 axis plays a crucial role in GC senescence and ovarian aging.
Keywords:
DNA-methyltransferase 1Senescencegranulosa cellmethylationovarian aging

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