||Si Wang, Yuxuan Zheng, Jingyi Li，Yang Yu, Weiqi Zhang，Moshi Song, Zunpeng Liu, Zheying Min, Huifang Hu, Ying Jing, Xiaojuan He, Liang Sun, Lifang Ma, Concepcion Rodriguez Esteban, Piu Chan, Jie Qiao, Qi Zhou, Jing Qu, Fuchou Tang,,Guang-Hui Liu
||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.