Evidence map›Paper›PMID 33070161›Full record

ArticlePediatric research2021

Chorioamnionitis induces changes in ovine pulmonary endogenous epithelial stem/progenitor cells in utero.

Helene Widowski, Daan R M G Ophelders, Anaïs J C N van Leeuwen, Peter G J Nikkels, Carmen A H Severens-Rijvers, Vanessa L S LaPointe, Jack P M Cleutjens, Matthias C Hütten, Matthew W Kemp, Matthew S Payne and 8 more

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In one paragraph

Article in Pediatric research, 2021. 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
0.3field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. 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

18 authors at 5 institutions in 4 countries.

Helene WidowskiDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Daan R M G OpheldersDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Anaïs J C N van LeeuwenDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Peter G J NikkelsDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Carmen A H Severens-RijversDepartment of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.
Vanessa L S LaPointeDepartment of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Jack P M CleutjensDepartment of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.
Matthias C HüttenNeonatology, Pediatrics Department, Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, The Netherlands.
Matthew W KempDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
Matthew S PayneDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
Masatoshi SaitoDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
Haruo UsudaDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
John P NewnhamDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
Alan H JobeDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, Australia.
Boris W KramerDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Tammo DelhaasDepartment of BioMedical Engineering, Maastricht University Medical Center, Maastricht, The Netherlands.
Tim G A M WolfsDepartment of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Niki L ReynaertDepartment of Respiratory Medicine, Maastricht University, Maastricht, The Netherlands. n.reynaert@maastrichtuniversity.nl.
Maastricht University · NLUniversity of Western Australia · AUTohoku University Hospital · JPUniversity Medical Center Utrecht · NLUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChorioamnionitis, an intrauterine infection of the placenta and fetal membranes, is a common risk factor for adverse pulmonary outcomes in premature infants including BPD, which is characterized by an arrest in alveolar development. As endogenous epithelial stem/progenitor cells are crucial for organogenesis and tissue repair, we examined whether intrauterine inflammation negatively affects these essential progenitor pools.

methodsIn an ovine chorioamnionitis model, fetuses were intra-amniotically exposed to LPS, 2d or 7d (acute inflammation) before preterm delivery at 125d of gestation, or to intra-amniotic Ureaplasma parvum for 42d (chronic inflammation). Lung function, pulmonary endogenous epithelial stem/progenitor pools, and downstream functional markers were studied.

resultsLung function was improved in the 7d LPS and 42d Ureaplasma groups. However, intrauterine inflammation caused a loss of P63+ basal cells in proximal airways and reduced SOX-9 expression and TTF-1+ Club cells in distal airways. Attenuated type-2 cell numbers were associated with lower proliferation and reduced type-1 cell marker Aqp5 expression, indicative for impaired progenitor function. Chronic Ureaplasma infection only affected distal airways, whereas acute inflammation affected stem/progenitor populations throughout the lungs.

conclusionsAcute and chronic prenatal inflammation improve lung function at the expense of stem/progenitor alterations that potentially disrupt normal lung development, thereby predisposing to adverse postnatal outcomes. IMPACT: In this study, prenatal inflammation improved lung function at the expense of stem/progenitor alterations that potentially disrupt normal lung development, thereby predisposing to adverse postnatal outcomes. Importantly, we demonstrate that these essential alterations can already be initiated before birth. So far, stem/progenitor dysfunction has only been shown postnatally. This study indicates that clinical protocols to target the consequences of perinatal inflammatory stress for the immature lungs should be initiated as early as possible and ideally in utero. Within this context, our data suggest that interventions, which promote function or repair of endogenous stem cells in the lungs, hold great promise.

Indexed as

AnimalsChorioamnionitisEpithelial CellsFemaleLungPregnancyPremature BirthSheepStem Cells

Identifiers

PMID33070161
OpenAlexW3092742330

What OpenQuestion holds

Textmetadata
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.