Evidence map›Paper›PMID 36070698›Full record

ArticleCell reports2022

Functional rewiring of G protein-coupled receptor signaling in human labor.

Abigail R Walker, Camilla B Larsen, Samit Kundu, Christina Stavrinidis, Sung Hye Kim, Asuka Inoue, David F Woodward, Yun S Lee, Roberta Migale, David A MacIntyre and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Stabilized DNature communications · 2025
    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

15 authors at 5 institutions in 3 countries.

Abigail R WalkerInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Camilla B LarsenInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Samit KunduInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK.
Christina StavrinidisInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Sung Hye KimInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK.
Asuka InoueGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
David F WoodwardDepartment of Bioengineering, Imperial College London, London, UK.
Yun S LeeInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK.
Roberta MigaleInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Stem Cell Biology and Developmental Genetics Laboratory, The Francis Crick Institute, London, UK.
David A MacIntyreInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK.
Vasso TerzidouInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK.
Francesca FanelliDepartment Life Sciences, University of Modena and Reggio Emilia, via Campi 103, 41125 Modena, Italy; Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, via Campi 287, 41125 Modena, Italy.
Shirin KhanjaniInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Reproductive Medicine Unit, University College London Hospital, London, UK.
Phillip R BennettInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes European Preterm Birth Research Centre, Imperial College London, London, UK. Electronic address: p.bennett@imperial.ac.uk.
Aylin C HanyalogluInstitute of Reproductive and Developmental Biology, Department Metabolism, Digestion and Reproduction, Imperial College London, London, UK. Electronic address: a.hanyaloglu@imperial.ac.uk.
Imperial College London · GBThe Francis Crick Institute · GBTohoku University · JPUniversity College Hospital · GBUniversity of Modena and Reggio Emilia · IT

Funding

Department of Health
6 · The paper itself

Abstract

Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk. Super-resolution imaging with computational modeling reveals OT-dependent reorganization of EP2-OTR complexes to favor conformations for Gαi over Gαs activation. A selective EP2 ligand, PGN9856i, activates the relaxatory/Gαs-cAMP pathway but not the pro-labor/inflammatory responses in term-pregnant myometrium, even following OT. Our study reveals a mechanism, and provides a potential therapeutic solution, whereby EP2-OTR functional associations could be exploited to delay preterm labor.

Indexed as

Labor, ObstetricObstetric Labor, PrematureFemaleHumansInfant, NewbornMyometriumPregnancyReceptors, OxytocinUterine ContractionReceptors, OxytocinCP: Cell biologycrosstalkEP2G protein-coupled receptorheteromermyometriumoxytocinpregnancypreterm labor

Identifiers

PMID36070698
PMCPMC9638024
OpenAlexW4294770870

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.