Scholarlink

<p>Natural aging affects the ovary, leading to declining function and age-related female infertility. This study investigated the role of theca-interstitial cells (TICs) in ovarian aging, a previously understudied area. Transcriptomic analysis of young and aged mouse ovaries revealed ribonucleotide reductase M2 (<i>Rrm2</i>)—a gene involved in DNA replication and repair—to be significantly downregulated in aged ovaries. Functional experiments revealed that <i>Rrm2</i> knockdown in TICs reduced DNA synthesis, induced G1-phase arrest, inhibited proliferation, and promoted early apoptosis. Additionally, it triggered DNA damage and cellular senescence by inactivating the PI3K/AKT/mTOR pathway and upregulating p21. In vivo, RRM2 inhibition reduced primordial follicle counts, induced ovarian DNA damage, and suppressed DNA repair gene expression. Overall, these findings highlight that <i>Rrm2</i> downregulation drives TIC senescence, suggesting that targeting somatic cell senescence may offer a therapeutic strategy to decelerate ovarian aging.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月9日

查看全文
  • Rula Sa,
  • Xiang Zhang,
  • Kesong Shi,
  • Baoluri Wang,
  • Haiquan Yu

摘要

Natural aging affects the ovary, leading to declining function and age-related female infertility. This study investigated the role of theca-interstitial cells (TICs) in ovarian aging, a previously understudied area. Transcriptomic analysis of young and aged mouse ovaries revealed ribonucleotide reductase M2 (Rrm2)—a gene involved in DNA replication and repair—to be significantly downregulated in aged ovaries. Functional experiments revealed that Rrm2 knockdown in TICs reduced DNA synthesis, induced G1-phase arrest, inhibited proliferation, and promoted early apoptosis. Additionally, it triggered DNA damage and cellular senescence by inactivating the PI3K/AKT/mTOR pathway and upregulating p21. In vivo, RRM2 inhibition reduced primordial follicle counts, induced ovarian DNA damage, and suppressed DNA repair gene expression. Overall, these findings highlight that Rrm2 downregulation drives TIC senescence, suggesting that targeting somatic cell senescence may offer a therapeutic strategy to decelerate ovarian aging.