Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

Area of Science:

• Reproductive biology
• Gerontology
• Genomics

Background:

• Female fertility declines with age due to poorly understood ovarian aging mechanisms.
• Ovarian aging impacts oocyte quality and somatic cell function.

Purpose of the Study:

• To elucidate the molecular mechanisms of ovarian aging and age-related fertility decline.
• To identify cell-type-specific changes in the aging ovary using single-cell transcriptomics.

Main Methods:

• Single-cell RNA sequencing of ovaries from young and aged non-human primates (NHPs).
• Identification and characterization of seven distinct ovarian cell types.
• Analysis of gene-expression dynamics and aging-associated transcriptional changes.

Main Results:

• Seven ovarian cell types, including oocytes and somatic cells, were identified with unique gene-expression profiles.
• Oocyte development stages were delineated into four subtypes based on gene expression.
• Disturbed antioxidant signaling and oxidative damage were observed in early-stage oocytes and granulosa cells from aged NHPs.
• Inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were confirmed in granulosa cells from aged women.

Conclusions:

• Oxidative damage is a key factor in primate ovarian aging and fertility decline.
• Cell-type-specific molecular mechanisms underlying ovarian aging have been identified.
• New diagnostic biomarkers and therapeutic targets for age-related human ovarian disorders may emerge from these findings.