title: Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth.
abstract: BACKGROUND
  Perinatal asphyxia (PA) is a major cause of neonatal mortality and morbidity. Research has shown that in rats fetal asphyxia (FA) can provoke neuroprotection against a subsequent more severe perinatal asphyctic insult. This is called fetal asphyctic preconditioning (PC). Our objective was to investigate alterations in the placental inflammatory phenotype associated with PC.
  
  
  METHODS
  FA was induced in the rat at embryonic day 17 by reversibly clamping the uterine circulation and PA was induced at birth by submersion of the uterine horns in a saline bath for 19 min. The effect of PC was studied by inducing FA at E17, followed by PA at E21. Placental TNF-α, IL-1β, IL-6 and IL-10 mRNA and protein levels were measured by qPCR and ELISA.
  
  
  RESULTS
  IL-1β mRNA increased in the labouring FA group, but IL-1β protein decreased after both FA and PA. In the PC group, IL-1β mRNA and protein levels were similar to controls. IL-6 protein increased 6 h after FA, however decreased 24 h after FA. IL-6 mRNA was higher in the labouring PA group. IL-10 protein decreased 24 h after FA. At birth, IL-10 mRNA increased in the PA group; however, IL-10 protein decreased in both the PA and the FA group. In the PC group, IL-10 mRNA and protein were similar to control levels.
  
  
  CONCLUSIONS
  Depleted protein concentrations of IL-10 and IL-1β after one single asphyctic insult were reversed after fetal asphyctic PC. In addition, PC placentas showed less up-regulation of IL-6 mRNA compared to the PA ones. This modulated placental inflammatory phenotype might contribute to the improved neonatal outcome showed after fetal asphyctic PC.
authors.affiliation: Department of Pediatrics - Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands; Child Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Sparnaaij
authors.affiliation: Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador; Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador.
authors.forename: Peter
authors.initials: P
authors.lastname: Chedraui
authors.affiliation: Department of Pediatrics - Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands; Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador.
authors.forename: Kim H
authors.initials: KH
authors.lastname: Liem
authors.affiliation: Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador.
authors.forename: Gustavo S
authors.initials: GS
authors.lastname: Escobar
authors.affiliation: Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador.
authors.forename: Jasson
authors.initials: J
authors.lastname: Espinoza-Caicedo
authors.affiliation: Department of Pediatrics - Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.affiliation: Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands; Child Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Johan S H
authors.initials: JS
authors.lastname: Vles
authors.affiliation: Department of Pediatrics - Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands; Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador; Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands. Electronic address: danilo.gavilanes@mumc.nl.
authors.forename: Antonio W D
authors.initials: AW
authors.lastname: Gavilanes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019194:Ischemic Preconditioning; D036801:Parturition / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines
keywords: Asphyxia; Fetal; Inflammation; Placenta; Preconditioning