Evidence map›Paper›PMID 41566072›Full record

ArticleCellular and molecular life sciences : CMLS2026

Hypoxic mesenchymal stem cell-Derived Exosomal circPTP4A2 improves granulosa cell mitochondrial function via YBX1.

Xiaolan Zhu, Xuyan Shi, Jingjing Lu, Wenxin Li, Yueqin Liu, Lin Jiang, Yanting Lv

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

7 authors.

Xiaolan Zhu *Department of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China. zxl2517@163.com.ORCID http://orcid.org/0000-0002-0499-8045
Xuyan Shi *Department of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.
Jingjing LuDepartment of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.
Wenxin LiDepartment of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.
Yueqin LiuDepartment of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.
Lin JiangDepartment of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.
Yanting LvDepartment of Reproductive Medical Center, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Maternity and Child Health Care Hospital), Zhenjiang, Jiangsu Province, 212001, China.

Funding

"333 Project" of Jiangsu Province "333 Project" of Jiangsu ProvinceNational Natural Science Foundation of China No. 82172838Natural Science Foundation of Jiangsu Province No. BK20241860
6 · The paper itself

Abstract

backgroundPremature ovarian insufficiency (POI) profoundly compromises female reproductive health through accelerated follicle depletion and endocrine disruption. Emerging evidence highlights the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-Exs), particularly when their function is enhanced by hypoxic preconditioning. In this study, the ability of hypoxia-preconditioned MSC-Exs (H-Exs) to ameliorate oxidative damage to granulosa cells (GCs) and restore ovarian function, was systematically evaluated, and a POI rat model was used to investigate the underlying mechanism.

methodsCircRNAs specifically expressed in H-Exs were identified and validated. The ability of H-Exs and their corresponding circPTP4A2 to repair oxidative damage and restore mitochondrial function were evaluated by antioxidant enzyme assays, reactive oxygen species (ROS) assays, JC-1 staining, ATP level assays, oxygen consumption rate (OCR) measurements and TEM. The interaction between circPTP4A2 and YBX1 was analysed by molecular dynamics simulations, RIP, CHX assays, and MG132 assays, and the restorative effect of the circPTP4A2/YBX1 axis on ovarian function was verified.

resultsOur findings revealed that compared with normoxic MSC-Exs (N-Exs), H-Exs exerted superior protective effects, significantly attenuating oxidative stress and restoring mitochondrial bioenergetics in KGN cells. Mechanistically, circPTP4A2 was identified as a hypoxia-responsive cargo selectively enriched in H-Exs. This circular RNA stabilized Y-box binding protein 1 (YBX1) through direct interaction, increasing its antioxidative capacity and mitochondrial regulatory functions. Hypoxia-inducible factor 1-alpha (HIF-1α) was further shown to transcriptionally upregulate circPTP4A2 via direct binding to the promoter region of its host gene PTP4A2.

conclusionThese results establish the circPTP4A2/YBX1 axis as a critical mediator of the therapeutic efficacy of H-Exs for POI, providing both mechanistic insights and a translational framework for exosome-based regenerative strategies.

Indexed as

ExosomesGranulosa CellsMesenchymal Stem CellsMitochondriaRNA, CircularY-Box-Binding Protein 1AnimalsCell HypoxiaFemaleHumansOxidative StressPrimary Ovarian InsufficiencyRatsRats, Sprague-DawleyReactive Oxygen SpeciesReactive Oxygen SpeciesRNA, CircularY-Box-Binding Protein 1CircPTP4A2ExosomesPOIYBX1; hypoxic

Identifiers

PMID41566072
PMCPMC12858719

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Registered trials

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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.