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Ovarian stiffness increases with age and tracks with declining egg yield

Researchers combined imaging, matrix profiling, and single-cell sequencing to show how ovarian fibrosis develops in women over time.

bioRxiv : the preprint server for biology · Hughes L et al. · Paper published 8 Sep 2026

Paper

In a preprint study of human female participants, researchers used multimodal profiling to characterize ovarian fibrosis in situ. The authors combined shear wave elastography, extracellular matrix neoepitope fingerprinting, and single-cell RNA sequencing of follicular fluid aspirates. In an initial cohort of 32 women aged 33 and younger or 37 and older, age predicted ovarian stiffness. Greater mean stiffness was independently associated with reduced oocyte yield and follicular efficiency. Extracellular matrix profiling showed an imbalance favoring tissue formation over degradation. Single-cell transcriptomics revealed an age-associated fibroinflammatory stromal program marked by pro-fibrotic signaling and stromal-immune crosstalk. A validation cohort of 100 women aged 25 to 45 years confirmed that ovarian stiffness increases with age.

Why it matters

Ovarian fibrosis represents a measurable feature of human reproductive aging that could serve as a non-invasive biomarker. Identifying these stromal changes also highlights prospective pathways for therapeutic interventions targeting female reproductive longevity.

Caveats

The findings are based on observational data across two cohorts totaling 132 women. In addition, the paper is a preprint that has not yet undergone peer review.

Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.

The paper

Multimodal profiling establishes ovarian fibrosis as a measurable and targetable hallmark of human reproductive aging

Hughes L, Zaniker-Gomez E, Devrukhkar PR et al.

bioRxiv : the preprint server for biology · 8 Sep 2026 · Preprint, not yet peer-reviewed

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Core geroscience
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Humans
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Preprint