Corrigendum: Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses.

[This corrects the article DOI: 10.3389/fimmu.2020.00189.].

Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses.

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 was 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 layers 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 S100ß 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 S100ß 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.

Chronic moderate hypoxia and protein malnutrition both induce growth retardation, but have distinct effects on arterial endothelium-dependent reactivity in the chicken embryo.

Deviations in the rate of intrauterine growth may change organ system development, resulting in cardiovascular disease in adult life. Arterial endothelial dysfunction often plays an important role in these diseases. The effects of two interventions that reduce fetal growth, chronic hypoxia and protein malnutrition, on arterial endothelial function were investigated. Eggs of White Leghorn chickens were incubated either in room air or in 15% O2 from d 6 until d 19 of the 21-d incubation. Protein malnutrition was induced by removal of 10% of the total albumen content at d 0. In vitro reactivity of the femoral artery in response to vasodilators was measured at d 19. Both chronic hypoxia and protein malnutrition reduced embryonic body weight at d 19 by 14% without affecting relative brain weight. Chronic hypoxia or protein malnutrition did not change sensitivity to the exogenous nitric oxide donor, sodium nitroprusside (5.74 +/- 0.15 versus 5.85 +/- 0.23 and 6.05 +/- 0.18 versus 6.01 +/- 0.34, respectively). Whereas protein malnutrition did not modify arterial sensitivity to acetylcholine (7.00 +/- 0.10 versus 7.12 +/- 0.05), chronic hypoxia reduced sensitivity to this endothelium-dependent vasodilator (6.57 +/- 0.07 versus 7.02 +/- 0.06). In the presence of Nomega-nitro-l-arginine methyl ester, this difference in sensitivity to acetylcholine was no longer apparent (6.31 +/- 0.13 versus 6.27 +/- 0.06), indicating that chronic exposure to hypoxia reduced sensitivity to acetylcholine by lowering nitric oxide release. In additional experiments, a decrease in basal nitric oxide release in arteries of 3- to 4-wk-old chickens that had been exposed to in ovo chronic hypoxia was observed (increase in K+ contraction: -0.16 +/- 0.33 N/m versus 0.68 +/- 020 N/m). Protein malnutrition and chronic hypoxia both induce disproportionate growth retardation, but only the latter impairs arterial endothelial function. Intrauterine exposure to chronic hypoxia induces changes in arterial endothelial properties that may play a role in the development of cardiovascular disease in adult life.