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Updated: Jul 6, 2025
Accurate Follicle Enumeration in Adult Mouse Ovaries
Published on: October 16, 2020
A single-cell atlas of the aging mouse ovary
José V V Isola1, Sarah R Ocañas2,3,4,5, Chase R Hubbart1
1Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Abstract:
Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds to declines in oocyte quality. Despite a growing body of work, the field lacks a comprehensive cellular map of the transcriptomic changes in the aging mouse ovary to identify early 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 lymphocyte proportions increasing the most, which was confirmed by flow cytometry. We also found an age-related downregulation of collagenase pathways in stromal fibroblasts, which corresponds to rises in ovarian fibrosis. Follicular cells displayed stress-response, immunogenic and fibrotic signaling pathway inductions with aging. This report provides critical insights into mechanisms responsible for ovarian aging phenotypes. The data can be explored interactively via a Shiny-based web application.
Insights
Ovarian aging accelerates fertility decline due to increased immune cells and fibrosis. This study maps transcriptomic changes in aging mouse ovaries, revealing early cellular drivers of reproductive aging.
Area of Science:
- Reproductive biology and aging research.
- Genomics and transcriptomics.
- Immunology and fibrosis.
Background:
- Ovarian aging significantly impacts female fertility and health, preceding complete follicular loss.
- Existing research lacks a detailed cellular-level understanding of transcriptomic shifts in aging ovaries.
- Early identification of aging mechanisms is crucial for reproductive health interventions.
Purpose of the Study:
- To create a comprehensive transcriptomic cell map of the aging mouse ovary.
- To identify early molecular and cellular drivers of ovarian aging.
- To understand the mechanisms behind age-related fertility decline.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of ovarian tissue from young (3-month) and aged (9-month) mice.
- Comparative transcriptomic analysis to identify age-related gene expression changes.
- Flow cytometry validation of immune cell population shifts.
Main Results:
- A significant increase in immune cell populations, particularly lymphocytes, was observed in aged ovaries.
- Stromal fibroblasts showed age-related downregulation of collagenase pathways, correlating with increased ovarian fibrosis.
- Follicular cells exhibited induced stress-response, immunogenic, and fibrotic signaling pathways with aging.
Conclusions:
- Aging mouse ovaries exhibit distinct transcriptomic and cellular alterations, including immune cell infiltration and fibrosis.
- These changes in follicular and stromal cells provide critical insights into the mechanisms driving ovarian aging phenotypes.
- The findings offer a foundation for understanding and potentially mitigating age-related fertility decline.
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