International Journal of Molecular Sciences

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Dear Colleagues,

Neonates can face various perinatal injurious events including infections, placental dysfunction, disrupted oxygen supply, and alterations in blood flow and mechanical ventilation, and these injurious events around birth have been identified as important risk factors for the development of adverse outcomes in later life. Although our understanding of the pathophysiological processes in the compromised neonate has increased enormously in recent years, therapeutic options in the clinic to improve neonatal outcome in the perinatal period are still limited. Therefore, there is a great need to improve our understanding of the underlying mechanisms leading to these adverse outcomes upon a bad start in life. This renewed knowledge can then be used to identify new therapeutic targets to improve short- and long-term outcomes of the vulnerable neonate. Therefore, this Special Issue aims to gather high-quality research manuscripts or reviews that focus on the molecular and cellular mechanisms in the course of injurious perinatal events that predispose to postnatal diseases throughout life.

Dr. Tim G. A. M. Wolfs
Guest Editor

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Keywords

compromised neonate
infections
placental dysfunction
disrupted oxygen supply
molecular and cellular mechanisms

Published Papers (1 paper)

Research

25 pages, 15791 KiB

Open AccessArticle

Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies

by Charlotte van Gorp, Ilse H. de Lange, Matthias C. Hütten, Carmen López-Iglesias, Kimberly R. I. Massy, Lilian Kessels, Kèvin Knoops, Iris Cuijpers, Mireille M. J. P. E. Sthijns, Freddy J. Troost, Wim G. van Gemert, Owen B. Spiller, George M. H. Birchenough, Luc J. I. Zimmermann and Tim G. A. M. Wolfs

Int. J. Mol. Sci. 2024, 25(7), 4000; https://doi.org/10.3390/ijms25074000 - 03 Apr 2024

Viewed by 628

Abstract

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology in the Compromised Neonate)

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