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Status |
Public on Nov 27, 2023 |
Title |
A single-cell atlas of the aging murine ovary |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Ovarian aging leads to diminished fertility, dysregulated endocrine signaling, and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Around 35 years old, women experience a sharp decline in fertility, corresponding to declines in oocyte quality. However, the field lacks a cellular map of the transcriptomic changes in the aging ovary to identify drivers of ovarian decline. To fill this gap, we performed single-cell RNA sequencing on ovarian tissue from young (3-month-old) and reproductively aged (9-month-old) mice. Our analysis revealed a doubling of immune cells in the aged ovary, with T and B lymphocyte proportions increasing most. We also discovered an age-related upregulation of alternative macrophage and downregulation of collagenase pathways in stromal fibroblasts. Overall, follicular cells (especially granulosa and theca) display stress response, immunogenic, and fibrotic signaling pathway inductions with aging. These changes are more exaggerated in the atretic granulosa cells but are also observed in healthy antral and preantral granulosa cells. Moreover, we did not observe age-related changes in markers of cellular senescence in any cellular population with advancing age, despite specific immune cells expressing senescence-related genes across both timepoints. This report raises several new hypotheses that could be pursued to elucidate mechanisms responsible for ovarian aging phenotypes.
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Overall design |
scRNA-Seq from dissociated ovaries from young (3 months old; n=4) and reproductively aged (9 months old; n=4) wild-type C57BL/6j mice
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Contributor(s) |
Isola JV, Ocañas SR, Hubbart CR, Ko S, AliMondal S, Hense JD, Schneider A, Kovats S, Freeman WM, Stout MB |
Citation(s) |
38200272 |
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Submission date |
May 11, 2023 |
Last update date |
May 09, 2024 |
Contact name |
Michael Stout |
E-mail(s) |
michael-stout@omrf.org
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Organization name |
Oklahoma Medical Research Foundation
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Department |
Aging and Metabolism
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Street address |
825 N.E. 13th Street
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City |
Oklahoma City |
State/province |
OK |
ZIP/Postal code |
73104 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (8)
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GSM7325159 |
Ovary, 3 months, 4 |
GSM7325160 |
Ovary, 9 months, 5 |
GSM7325161 |
Ovary, 9 months, 6 |
GSM7325162 |
Ovary, 9 months, 7 |
GSM7325163 |
Ovary, 9 months, 8 |
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Relations |
BioProject |
PRJNA971592 |
Supplementary file |
Size |
Download |
File type/resource |
GSE232309_Endothelial_Epithelial_Cells.rds.gz |
73.1 Mb |
(ftp)(http) |
RDS |
GSE232309_Granulosa_Cells.rds.gz |
278.7 Mb |
(ftp)(http) |
RDS |
GSE232309_Immune_Cells.rds.gz |
77.5 Mb |
(ftp)(http) |
RDS |
GSE232309_RAW.tar |
690.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
GSE232309_Stroma_Cells.rds.gz |
367.4 Mb |
(ftp)(http) |
RDS |
GSE232309_age.combined.RDS.gz |
973.5 Mb |
(ftp)(http) |
RDS |
gse232309_GEO_update_2024-05-08.xlsx |
10.1 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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