Cited by 373Reproductive Biology and FertilityOvarian function and disordersOvarian cancer diagnosis and treatment

Reproductive age-associated fibrosis in the stroma of the mammalian ovary

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Briley, Shawn M, Jasti, Susmita, McCracken, Jennifer M, Hornick, Jessica E, Fegley, Barbara, Pritchard, Michele T, Duncan, Francesca E·2016·Reproduction

Abstract

Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis – or the excess accumulation of ECM – can disrupt tissue architecture and function. Several organs, including the heart, lung and kidney, exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies aging in the ovary – an organ that ages chronologically before other organs. We used Picrosirius Red (PSR), a connective tissue stain specific for collagen I and III fibers, to evaluate ovarian fibrosis. Using bright-field, epifluorescence, confocal and polarized light microscopy, we validated the specific staining of highly ordered PSR-stained fibers in the ovary. We next examined ovarian PSR staining in two mouse strains (CD1 and CB6F1) across an aging continuum and found that PSR staining was minimal in ovaries from reproductively young adult animals, increased in distinct foci in animals of mid-to-advanced reproductive age, and was prominent throughout the stroma of the oldest animals. Consistent with fibrosis, there was a reproductive age-associated increase in ovarian hydroxyproline content. We also observed a unique population of multinucleated macrophage giant cells, which are associated with chronic inflammation, within the ovarian stroma exclusively in reproductively old mice. In fact, several genes central to inflammation had significantly higher levels of expression in ovaries from reproductively old mice relative to young mice. These results establish fibrosis as an early hallmark of the aging ovarian stroma, and this altered microenvironment may contribute to the age-associated decline in gamete quality.

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  • The ovary exhibits age-dependent inflammation and fibrosis, but whether these are associated with senescence has not been conclusively established.

    “Additionally, the ovary exhibits age-dependent inflammation and fibrosis234–237; however, whether these are associated with senescence has not been conclusively established.”

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Authors
Briley, S. M., Jasti, S., McCracken, J. M., Hornick, J. E., Fegley, B., Pritchard, M. T., & Duncan, F. E.
Affiliations
  • University of Kansas Medical Center (US)
  • Northwestern University (US)
Corresponding author
Duncan, Francesca E
Venue
Reproduction
Published
2016-09-01
Volume
152
Issue
3
Pages
245-260
ISSN
  • 1470-1626 (ISSN-L)
  • 1741-7899
OpenAlex
W2497766038
Cited by
373
References
76
Citations by year
2026: 53 · 2025: 64 · 2024: 77 · 2023: 50 · 2022: 39 · 2021: 25 · 2020: 26 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 1
FWCI
12.89
Type
journal article
Language
en
Open access
Locations
  • Reproduction (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (P20GM103549, P20GM104936, P20GM103418)
  • National Institute of Environmental Health Sciences (T32ES007079)
  • National Center for Research Resources (P20RR021940, S10RR027564)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD002528, P50HD076188)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
Keywords
ovarian aging, ovarian fibrosis, ovarian stroma, extracellular matrix, collagen I and III, picrosirius red staining, hydroxyproline, chronic inflammation, mouse model
MeSH terms
Aging, Animals, Azo Compounds, Cells, Cultured, Coloring Agents, Extracellular Matrix, Female, Fibrosis, Ovary, Reproduction, Stromal Cells, Inflammation Mediators, Mice

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