Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics
Received date: 04 Oct 2023
Accepted date: 29 Oct 2023
Published date: 15 May 2024
Copyright
The ovary is indispensable for female reproduction, and its age-dependent functional decline is the primary cause of infertility. However, the molecular basis of ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries. From a global view, somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region, likely constituting a hostile microenvironment that facilitates ovarian aging. Further, we uncovered that inflammation, the senescent-associated secretory phenotype, senescence, and fibrosis are the likely primary contributors to ovarian aging (PCOA). Of note, we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2 (Metallothionein 2) highly expressing spot (MT2high) characterized by high levels of inflammation, potentially serving as an aging hotspot in the primate ovary. Moreover, with advanced age, a subpopulation of MT2high accumulates, likely disseminating and amplifying the senescent signal outward. Our study establishes the first primate spatiotemporal transcriptomic atlas, advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.
Key words： spatial transcriptome; primate; ovary; aging; senescence; inflammation
Huifen Lu , Ying Jing , Chen Zhang , Shuai Ma , Weiqi Zhang , Daoyuan Huang , Bin Zhang , Yuesheng Zuo , Yingying Qin , Guang-Hui Liu , Yang Yu , Jing Qu , Si Wang . Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics[J]. Protein & Cell, 2024 , 15(5) : 364 -384 . DOI: 10.1093/procel/pwad063
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