Evidence map›Paper›PMID 42593156›Full record

ArticleAging cell2026

Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging.

Xingyu Shen, Haiyang Wang, Gefei Cao, Yaelim Lee, Jin Zhu, Loo Chien Wang, Tianyun Zhao, Siok Ghee Ler, Radoslaw M Sobota, Rong Li and 1 more

Abstract read
In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Xingyu ShenMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.
Haiyang WangMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.ORCID https://orcid.org/0000-0002-6362-6022
Gefei CaoMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.
Yaelim LeeMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.
Jin ZhuMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.
Loo Chien WangBioprocessing Technology Institute, Singapore, Singapore.
Tianyun ZhaoInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Siok Ghee LerInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Radoslaw M SobotaInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Rong LiMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.
Jennifer L YoungMechanobiology Institute (MBI), National University of Singapore, Singapore, Singapore.ORCID https://orcid.org/0000-0002-5229-5168

Funding

Bia-Echo Asian Centre for Reproductive Longevity and EqualityMinistry of Education - SingaporeNational Research Foundation Singapore NRF-MSG-2023-0001
6 · The paper itself

Abstract

Female reproductive aging is associated with ovarian functional decline, leading to infertility. During aging, biochemical and biophysical changes in the ovarian extracellular matrix (ECM) occur, yet how these properties affect follicle growth and oocyte quality remains poorly understood. Here we describe spatiotemporal changes in the ovarian ECM with age using mass spectrometry, immunohistochemistry, and nanoindentation. While follicle stiffness remains unchanged, stromal matrix remodeling is associated with a ~2.5-fold increase in stiffness. To understand how this increase in stromal stiffness affects age-related follicular dysfunction, isolated young follicles were cultured in soft and stiff hydrogels mimicking young and aged ovarian stromal stiffness, respectively. Higher stiffness lead to a decrease in granulosa cell (GC) proliferation, oocyte quality, and GC-oocyte interactions mediated via transzonal projections (TZPs). RNA-seq revealed TGF-β signaling as a major pathway affected by stiffness, and activation of TGF-β signaling through Smad7 silencing rescued TZP formation and oocyte quality in stiff matrix. These findings provide mechanistic insight into how changes in ECM mechanics contribute to ovarian aging functional decline and reveal potential therapeutic targets to counter fertility loss associated with tissue aging and fibrosis.

Indexed as

AgingExtracellular MatrixOocytesOvarian FollicleAnimalsFemaleMiceSignal TransductionTransforming Growth Factor betaTransforming Growth Factor betainfertilityovarian stromastiffnessTGF‐βtranszonal projections

Identifiers

PMID42593156
PMCPMC13471645

What OpenQuestion holds

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Registered trials

None linked

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.