title: Intraamniotic lipopolysaccharide exposure changes cell populations and structure of the ovine fetal thymus.
abstract: BACKGROUND
  Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure.
  
  
  METHODS
  Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days).
  
  
  RESULTS
  The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor κB positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure.
  
  
  CONCLUSIONS
  Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.
authors: Department of Pediatrics, School for Oncology and Developmental Biology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Elke
authors: E
authors: Kuypers
authors: Tim G A M
authors: TG
authors: Wolfs
authors: Jennifer J P
authors: JJ
authors: Collins
authors: Reint K
authors: RK
authors: Jellema
authors: John P
authors: JP
authors: Newnham
authors: Matthew W
authors: MW
authors: Kemp
authors: Suhas G
authors: SG
authors: Kallapur
authors: Alan H
authors: AH
authors: Jobe
authors: Boris W
authors: BW
authors: Kramer
mesh_terms: D000653:Amniotic Fluid; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002821:Chorioamnionitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018836:Inflammation Mediators / Q000378:metabolism; D007267:Injections; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4
keywords: fetal inflammatory response syndrome; immune modulation; prematurity; thymic involution