Evidence map›Paper›PMID 30235305›Full record

ArticlePloS one2018

In silico analysis of the Mus musculus uterine gene expression landscape during pregnancy identifies putative upstream regulators for labour.

Febilla Fernando, Souad Boussata, Aldo Jongejan, Joris A van der Post, Gijs Afink, Carrie Ris-Stalpers

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. 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
0.2field-weighted citation impact, top 44% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. TBX2, a Novel Regulator of Labour.Medicina (Kaunas, Lithuania) · 2021
    Article
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

6 authors at 1 institution in 1 country.

Febilla FernandoReproductive Biology Laboratory Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Souad BoussataReproductive Biology Laboratory Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Aldo JongejanDepartment of Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Joris A van der PostWomen's and Children's Clinic, Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Gijs AfinkReproductive Biology Laboratory Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Carrie Ris-StalpersReproductive Biology Laboratory Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-8555-101X
Amsterdam University Medical Centers · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe molecular pathways involved in the transition from uterine quiescence to overt labour are mapped and form the currently established pharmacological targets for both the induction and inhibition of human labour. However, both spontaneous premature labour and functional dystocia occur and are difficult to treat adequately. The identification of upstream regulators involved in the onset and orchestration of labour pathways is essential to develop additional therapies that will contribute to the regulation of the timing of birth.

objectivesTo define uterine biological processes and their upstream activators involved in the transition from uterine quiescence to overt labour. STUDY

designThe uterus of non-pregnant and pregnant FVB M. musculus is collected at embryonic days (E) 6.5, 8.5, 10.5, 12.5, 15.5 and 17.5 and the uterine transcriptome is determined using the Illumina mouse Ref8v2 micro-array platform. K-means clustering and Ingenuity Pathway Analysis are applied to further dissect the transcriptome data.

resultsFrom E6.5 to E17.5, 5405 genes are significantly differentially expressed and they segregate into 7 unique clusters. Five of the 7 clusters are enriched for genes involved in specific biological processes that include regulation of gene-expression, T-cell receptor activation, Toll-like receptor signalling and steroid metabolism. The identification of upstream activators for differentially expressed genes between consecutive time points highlights the E10.5 to E12.5 window during which the role from progesterone switches from an activated state to the inhibited state reflecting the process of functional progesterone withdrawal essential for the transgression from myometrial quiescence to synchronized contractions. For this time window in which 189 genes are differentially expressed we define 22 putative upstream activators of which NUPR1 and TBX2 are the most significant with respectively an activated and an inhibited status.

conclusionsGene expression profiling of mice uterus from E6.5 to E17.5 results in 7 unique gene expression clusters from early to late pregnancy that define the landscape of molecular events in ongoing pregnancy. In the current dataset progesterone is predicted as an activated upstream regulator and maintainer of myometrial quiescence and is active till E10.5. Progesterone is predicted as an inhibited upstream regulator at E12.5. We identify 22 upstream regulators in the E10.5 to E12.5 time window where the switch to progesterone withdrawal occurs. They are putative relevant upstream activators of labour.

Indexed as

Gene Regulatory NetworksAnimalsComputer SimulationDystociaFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGestational AgeLabor, ObstetricMiceObstetric Labor, PrematureOligonucleotide Array Sequence AnalysisPregnancyUterus

Identifiers

PMID30235305
PMCPMC6147639
OpenAlexW2890309473

What OpenQuestion holds

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LicenceCC BY
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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.