Chronic intra-uterine Ureaplasma parvum infection induces injury of the enteric nervous system in ovine fetuses

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Author
Heymans, C.
de Lange, I.H.
Hütten, M.C.
Lenaerts, K.
de Ruijter, N.J.E.
Kessels, L.
Rademakers, G.
Melotte, V.
Boesmans, W.
Saito, Masatoshi
Usuda, Haruo
Stock, S.J.
Spiller, O.B
Beeton, Michael L.
Date
2020-03-17Acceptance date
2020-01-24
Type
Article
Publisher
Frontiers Media
ISSN
1664-3224
Metadata
Show full item recordAbstract
Background: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often
caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be
either acute or chronic, and is associated with adverse postnatal outcomes of the intestine, including
necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the
intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells.
Yet, the impact of acute, chronic or repetitive antenatal inflammatory stimuli on the development of
the intestinal mucosa and ENS has not been studied. The aim of this study is therefore to investigate
the effect of acute, chronic and repetitive microbial exposure on the intestinal mucosa, submucosa
and ENS in premature lambs.
Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa
and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute),
Ureaplasma parvum (UP) for 42 days (chronic) or repetitive microbial exposure (42 days UP with 2
or 7 days LPS).
Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and
inflammation in the mucosal and submucosal layer of the gut. Repetitive microbial exposure did not
further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural
ENS alterations characterized by loss of PGP9.5 and S100β immunoreactivity whereas these changes
were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days.
Conclusion: The in utero loss of PGP9.5 and S100β immunoreactivity following chronic UP
exposure corresponds with intestinal changes in neonates with NEC, and may therefore form a novel
mechanistic explanation for the association of chorioamnionitis and NEC.
Journal/conference proceeding
Frontiers in Immunology;
Citation
Heymans, C. et al. (2020) 'Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses', Frontiers in Immunology. DOI: 10.3389/fimmu.2020.00189.
Description
Article published in Frontiers in Immunology on 17 March 2020, available open access at: https://doi.org/10.3389/fimmu.2020.00189.
Sponsorship
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
This work was supported by the National Institutes of Health (Bethesda, MD, USA) grant (HD 57869) and the Kinderonderzoekfonds Limburg (TW).
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