Spatially resolved transcriptomic profiling of ovarian aging in mice

Area of Science:

• Reproductive biology
• Genomics
• Aging research

Background:

• Ovarian aging is the primary cause of female age-related infertility.
• The biological mechanisms driving ovarian aging are not fully understood.
• Previous bulk RNA-sequencing studies masked the ovary's cellular heterogeneity.

Purpose of the Study:

• To spatially resolve the transcriptomic landscape of ovaries from young and aged mice.
• To identify cell-population-specific changes associated with ovarian aging.
• To gain a deeper understanding of age-related fertility decline.

Main Methods:

• Spatial transcriptomics was employed on ovaries from young and aged outbred mice.
• Eight distinct ovarian cell populations were defined.
• Sub-cluster analysis was performed to identify cell-specific transcriptomic alterations.

Main Results:

• Significant transcriptomic changes were observed in all eight ovarian cell populations between young and aged samples.
• Distinct transcriptomes were identified for granulosa cell populations in young versus aged mice.
• An oocyte sub-cluster population present in young ovaries was absent in aged ovaries.

Conclusions:

• Spatial transcriptomics provides a novel perspective on mammalian ovarian aging.
• Cellular heterogeneity and localization are critical for understanding age-related fertility decline.
• This study highlights specific cellular mechanisms contributing to age-related infertility.