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Updated: May 31, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

VDR-Spermidine Axis Protects Against Age-Related Granulosa Cell Dysfunction and Follicular Decline via DNMTs-Mediated

Haiyun Chen1,2, Qinghe Geng3,4, Qiuyi Wang5

  • 1Department of Clinical Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu, PR China.

International Journal of Biological Sciences
|May 29, 2026
PubMed

Insights

The vitamin D receptor (Vdr) protects against ovarian aging by maintaining spermidine levels. Supplementing with spermidine or SAM delays aging and improves fertility in aged mice.

Area of Science:

  • Reproductive Biology
  • Aging Research
  • Molecular Endocrinology

Background:

  • Ovarian aging involves decreased follicle quantity and quality, with underlying mechanisms poorly understood.
  • The vitamin D receptor (Vdr) is implicated in cellular aging processes.
  • Granulosa cells (GCs) play a critical role in ovarian function and are affected by aging.

Purpose of the Study:

  • To investigate the role of the vitamin D receptor (Vdr) in ovarian aging.
  • To identify molecular pathways linking Vdr to GC aging and ovarian dysfunction.
  • To explore potential therapeutic interventions for age-related female infertility.

Main Methods:

  • Generated GCs-specific Vdr knockout (cVKO) mice and a Vdr-knockout (VKO) human granulosa-like cell line.
  • Performed integrated transcriptomic and metabolomic analyses.
  • Supplemented Vdr-deficient models and aged mice with spermidine (SPD) or S-adenosylmethionine (SAM).

Main Results:

  • Loss of Vdr accelerated GC aging and impaired ovarian function.
  • Vdr deficiency suppressed de novo spermidine biosynthesis by downregulating ODC1.
  • SPD depletion inhibited DNA methyltransferase (DNMTs) activity, leading to p53 pathway activation.
  • SPD or SAM supplementation rescued cellular aging, improved hormonal profiles, and promoted follicular development in cVKO mice.
  • Both supplements delayed ovarian aging and improved fertility in naturally aged mice.

Conclusions:

  • The Vdr-spermidine-DNMTs axis is crucial for preventing ovarian aging.
  • Vdr acts as an anti-aging transcription factor in GCs, regulating SPD synthesis.
  • SPD and SAM are promising therapeutic agents for age-related female infertility.
Keywords:
DNMTsmethylationovarian agingspermidine

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