title: Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner.
abstract: Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.
authors.affiliation: Department of Neonatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA.
authors.forename: T G A M
authors.initials: TG
authors.lastname: Wolfs
authors.forename: S G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: C L
authors.initials: CL
authors.lastname: Knox
authors.forename: G
authors.initials: G
authors.lastname: Thuijls
authors.forename: I
authors.initials: I
authors.lastname: Nitsos
authors.forename: G R
authors.initials: GR
authors.lastname: Polglase
authors.forename: J J P
authors.initials: JJ
authors.lastname: Collins
authors.forename: E
authors.initials: E
authors.lastname: Kroon
authors.forename: J
authors.initials: J
authors.lastname: Spierings
authors.forename: N F
authors.initials: NF
authors.lastname: Shroyer
authors.forename: J P
authors.initials: JP
authors.lastname: Newnham
authors.forename: A H
authors.initials: AH
authors.lastname: Jobe
authors.forename: B W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000818:Animals; D002821:Chorioamnionitis / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage; D007375:Interleukin-1 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000196:embryology / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000196:embryology* / Q000276:immunology / Q000382:microbiology*; D054892:Metagenome / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000382:microbiology; D034561:Sheep, Domestic; D014509:Ureaplasma; D016869:Ureaplasma Infections / Q000150:complications*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1