Abstract
Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging pro-cess,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in goats.Therefore,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.Results For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression signa-tures.Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological pro-cesses,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the anti-oxidant system,oxidative phosphorylation,and apoptosis.Subsequently,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of GCs.Additionally,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.
基金项目
National Key Research and Development Program of China(2022YFD1300202)
Technology Innovation and Application Development Special Project of Chongqing(cstc2021jscxgksbX0008)
National Natural Science Foundation of China(32102623)
National Natural Science Foundation of Chongqing(cstc2021jcyjmsxmX0875)
PhD Train Scientific Research Project of Chongqing(CSTB2022BSXM-JCX0002)
维普
万方数据