ArticleInternational journal of molecular sciences2021
Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality.Biology of reproduction · 2022Pooled it
- Full-length transcriptomic profiling reveals age-associated isoform remodeling and altered coding potential in the mouse ovary.Journal of ovarian research · 2026Article
- From germline immortality to somatic rejuvenation: Unlocking the ovarian blueprint for longevity.PLoS biology · 2026Article
- Extracellular matrix: new insights into its role in female reproductive aging and potential therapeutic strategies.npj aging · 2026Review
- Multicellular origins of murine ovarian inflammaging.Communications biology · 2026Article
- Senescence-Linked Fibrosis in the Aging Human Ovary Revealed by p16-Based Histological Profiling and Spatial Transcriptomics.Research square · 2026Article
- Research Hotspots and Emerging Frontiers in Ovarian Aging: A Bibliometric Analysis (2006-2025).Endocrine, metabolic & immune disorders drug targets · 2026Review
- Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.Reproductive biology and endocrinology : RB&E · 2025Review
- Microscale pressure measurements and optical coherence tomography reveal time-dependent biomechanical stages of ovulation in mice.iScience · 2025Article
- Review
- Modeling the extension of ovarian function after therapeutic targeting of the primordial follicle reserve.Human reproduction update · 2025Review
- Single-cell analysis of ovarian myeloid cells identifies age-associated changes in macrophages and signaling dynamics†.Biology of reproduction · 2025Article
- A Comprehensive Multiomics Signature of Doxorubicin-Induced Cellular Senescence in the Postmenopausal Human Ovary.Aging cell · 2025Article
- Biological Aging and Uterine Fibrosis in Cattle: Reproductive Trade-Offs from Enhanced Productivity.Cells · 2025Review
- Mast cell tryptase-PAR2 axis promotes ovarian fibrosis through RNF152-mediated stabilization of Bcl-xL.Journal of ovarian research · 2025Article
- Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.PLoS biology · 2025Article
- Article
- Ovarian Mechanobiology: Understanding the Interplay Between Mechanics and Follicular Development.Cells · 2025Review
- Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses.Nature aging · 2025Article
- Hallmarks of female reproductive aging in physiologic aging mice.Nature aging · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The female reproductive system ages before any other organ system in the body. This phenomenon can have tangible clinical implications leading to infertility, miscarriages, birth defects and systemic deterioration due to estrogen loss. "Fibroinflammation" is a hallmark of aging tissues; there is an increase in inflammatory cytokines and fibrotic tissue in the aging ovarian stroma. We systematically evaluated immunomodulatory factors in human follicular fluid, which, like the stroma, is a critical ovarian microenvironment directly influencing the oocyte. Using a cytokine antibody array, we identified a unique fibroinflammatory cytokine signature in follicular fluid across an aging series of women (27.7-44.8 years). This signature (IL-3, IL-7, IL-15, TGFβ1, TGFβ3 and MIP-1) increased with chronologic age, was inversely correlated to anti-Müllerian hormone (AMH) levels, and was independent of body mass index (BMI). We focused on one specific protein, TGFβ3, for further validation. By investigating this cytokine in human cumulus cells and ovarian tissue, we found that the age-dependent increase in TGFβ3 expression was unique to the ovarian stroma but not other ovarian sub-compartments. This study broadens our understanding of inflammaging in the female reproductive system and provides a defined fibroinflammatory aging signature in follicular fluid and molecular targets in the ovary with potential clinical utility.
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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.