Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

Cell. 2020 Feb 6;180(3):585-600.e19. doi: 10.1016/j.cell.2020.01.009. Epub 2020 Jan 30.


Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.

Keywords: aging; antioxidant gene; granulosa cell; oocyte; ovary; primate; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics*
  • Animals
  • Antioxidants / metabolism
  • Apoptosis / physiology
  • Atlases as Topic
  • Biomarkers
  • Cell Line, Tumor
  • Female
  • Granulosa Cells / metabolism
  • Humans
  • Macaca fascicularis
  • Oocytes / metabolism
  • Ovary / physiology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Single-Cell Analysis / methods*
  • Transcriptome*


  • Antioxidants
  • Biomarkers
  • Reactive Oxygen Species