ArticleAging cell2020
Ovarian stiffness increases with age in the mammalian ovary and depends on collagen and hyaluronan matrices.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 3 of them syntheses that pooled it.
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Who cites it
183 citing papers in PubMed, 3 syntheses or guidelines pooled it, 261 citations in OpenAlex.
- Beyond apoptosis: evidence of other regulated cell death pathways in the ovary throughout development and life.Human reproduction update · 2023Pooled it
- Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review.Human reproduction update · 2023Pooled it
- Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality.Biology of reproduction · 2022Pooled it
- Novel multi-omic biomarkers to combat oocyte and ovarian aging.GeroScience · 2026Article
- Standardizing Cell Ontology terms for cross-study integration in the female reproductive tract.Science advances · 2026Review
- The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause.Aging cell · 2026Article
- Multimodal profiling establishes ovarian fibrosis as a measurable and targetable hallmark of human reproductive aging.Research square · 2026Article
- The Fibro-Inflammatory Ovary: Stromal Fibrosis, Extracellular Matrix Remodeling, and Mechanotransduction in Female Infertility.Current issues in molecular biology · 2026Review
- New Hyaluronic Acid-Based Bioengineered 3D Scaffold: Fabrication and Potential for Oocyte In Vitro Maturation.Biotechnology and bioengineering · 2026Article
- Elevated contractility drives implantation failure in mouse embryos from aged females.Nature cell biology · 2026Article
- Hardened ground: ECM stiffness as a unifying biomechanical driver of reproductive stem cell aging.Biogerontology · 2026Review
- Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging.Aging cell · 2026Article
- Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- From Cytoskeletal Remodeling to Oocyte Quality: The Emerging Role of Mechanics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Modulating IL-11-dependent matrix stiffness to delay ovarian aging.Nature aging · 2026Article
- Cumulus Expansion and Oocyte Quality Across the Pubertal Transition in Mice: Implications for Modeling Fertility Preservation in Adolescents.Research square · 2026Article
- Aging disrupts spatiotemporal coordination in the cycling murine ovary.Nature aging · 2026Article
- Multi-contrast optical coherence tomography forBiomedical optics express · 2026Article
- HucMSC-mediated stromal metabolic reprogramming in reactivating aged ovaries: a single-cell transcriptomic perspective.Cellular & molecular biology letters · 2026Article
- Single-nucleus profiling reveals age-associated remodeling opposed by parity in the postmenopausal human ovary.bioRxiv : the preprint server for biology · 2026Article
123 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibrosis is a hallmark of aging tissues which often leads to altered architecture and function. The ovary is the first organ to show overt signs of aging, including increased fibrosis in the ovarian stroma. How this fibrosis affects ovarian biomechanics and the underlying mechanisms are unknown. Using instrumental indentation, we demonstrated a quantitative increase in ovarian stiffness, as evidenced by an increase in Young's modulus, when comparing ovaries from reproductively young (6-12 weeks) and old (14-17 months) mice. This ovarian stiffness was dependent on collagen because ex vivo enzyme-mediated collagen depletion in ovaries from reproductively old mice restored their collagen content and biomechanical properties to those of young controls. In addition to collagen, we also investigated the role of hyaluronan (HA) in regulating ovarian stiffness. HA is an extracellular matrix glycosaminoglycan that maintains tissue homeostasis, and its loss can change the biomechanical properties of tissues. The total HA content in the ovarian stroma decreased with age, and this was associated with increased hyaluronidase (Hyal1) and decreased hyaluronan synthase (Has3) expression. These gene expression differences were not accompanied by changes in ovarian HA molecular mass distribution. Furthermore, ovaries from mice deficient in HAS3 were stiffer compared to age-matched WT mice. Our results demonstrate that the ovary becomes stiffer with age and that both collagen and HA matrices are contributing mechanisms regulating ovarian biomechanics. Importantly, the age-associated increase in collagen and decrease in HA are conserved in the human ovary and may impact follicle development and oocyte quality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.