Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

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 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. We collected ~3,500 single cells from the ovary of 4 young (YF1, YF2, YF3 and YF4) and 4 aged monkeys (OF1, OF2, OF3 and OF4) and performed single-cell RNA-seq sequencing. We have also collected IDH1- and NDUFB10-knockdown KGN cells (a human granulosa cell line) (samples labelled with 'IDH1' or 'NDUFB10'), and KGN cells transfected with negative control duplex (samples labelled with 'NC'). These three types were cultured with or without H2O2 treatment: H2O2-treated group (samples labelled with 'H2O2') and untreated group (samples labelled with 'B').