Evidence map›Paper›PMID 34416903›Full record

ArticleJournal of translational medicine2021

Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus.

Soumyalekshmi Nair, Dominic Guanzon, Nanthini Jayabalan, Andrew Lai, Katherin Scholz-Romero, Priyakshi Kalita de Croft, Valeska Ormazabal, Carlos Palma, Emilio Diaz, Elizabeth A McCarthy and 9 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Crosstalk of extracellular vesicles in maternal-fetal interaction.Frontiers in cell and developmental biology · 2026
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  16. The role of microRNAs in pregnancies complicated by maternal diabetes.Clinical science (London, England : 1979) · 2024
    Review
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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

19 authors at 5 institutions in 3 countries.

Soumyalekshmi NairExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Dominic GuanzonExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Nanthini JayabalanExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Andrew LaiExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Katherin Scholz-RomeroExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Priyakshi Kalita de CroftExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Valeska OrmazabalFaculty of Biological Sciences, Pharmacology Department, University of Concepcion, Concepción, Chile.
Carlos PalmaExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Emilio DiazFaculty of Medicine, Department of Obstetrics and Gynaecology, University of Concepcion, Concepción, Chile.
Elizabeth A McCarthyDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
Alexis ShubDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
Jezid MirandaFetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia Obstetricia i Neonatologia, Universitat de Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Eduard GratacósFetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia Obstetricia i Neonatologia, Universitat de Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Fátima CrispiFetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Institut Clínic de Ginecologia Obstetricia i Neonatologia, Universitat de Barcelona, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Gregory DuncombeExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Martha LappasDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
H David McIntyreMater Research, Faculty of Medicine, University of Queensland, Mater Health, South Brisbane, Australia.
Gregory RiceExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.
Carlos SalomonExosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia. c.salomongallo@uq.edu.au.ORCID 0000-0003-4474-0046
The University of Queensland · AUCentre for Biomedical Network Research on Rare Diseases · ESThe University of Melbourne · AUUniversity of Concepción · CLMater Health Services · AU

Funding

Fondo Nacional de Desarrollo Científico y Tecnológico 1170809National Health and Medical Research Council 1195451
6 · The paper itself

Abstract

backgroundGestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile.

methodsDiscovery: A retrospective, case-control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM.

resultsA total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake.

conclusionsDuring early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.

Indexed as

Diabetes, GestationalExtracellular VesiclesMicroRNAsCase-Control StudiesFemaleHumansJanus KinasesLongitudinal StudiesPlacentaPregnancyRetrospective StudiesSignal TransductionSTAT Transcription FactorsJanus KinasesMicroRNAsMIRN92 microRNA, humanSTAT Transcription FactorsExosomesInsulin resistancemiRNAsPregnancySkeletal muscle

Identifiers

PMID34416903
PMCPMC8377872
OpenAlexW3134757070

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.