Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth |
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| Institution: | 1. Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, Maastricht, The Netherlands;2. Institute of Biomedicine, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador;3. Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador;4. Department of Neuropsychology – Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands;5. Child Neurology, Maastricht University Medical Center, Maastricht, The Netherlands;1. The Hospital for Sick Children and University of Toronto, Department of Pediatrics (Division of Neurology), Toronto, ON M5G 1X8, Canada;2. Neurosciences and Mental Health, SickKids Research Institute, Toronto, ON M5G 0A4, Canada;3. The Hospital for Sick Children and University of Toronto, Department of Diagnostic Imaging, Toronto, ON M5G 1X8, Canada;4. The Hospital for Sick Children and University of Toronto, Department of Pediatrics (Division of Neonatology), Toronto, ON M5G 1X8, Canada;1. Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;2. Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;1. Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK;2. Department of Obstetrics and Gynaecology, University Medical Centre of Groningen, University of Groningen, The Netherlands;3. Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK;4. Department of Engineering, University of Cambridge, Cambridge, UK;1. Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, Hatfield, Hertfordshire, AL9 7TA, United Kingdom;2. Rossdales Equine Practice, Beaufort Cottage Stables, High Street, Newmarket, Suffolk CB8 8JS, United Kingdom;3. Equine Reproductive Services (UK) Ltd., 33 Westgate, Old Malton, Malton, North Yorkshire, YO17 7HE, United Kingdom;4. Newmarket Equine Hospital, Cambridge Road, Newmarket, Suffolk, CB8 0FG, United Kingdom;5. Department of Production and Population Health, The Royal Veterinary College, Hawkshead Lane, Hatfield, Hertfordshire, AL9 7TA, United Kingdom;1. Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, 1142, New Zealand;2. Maternal Fetal Medicine, Auckland City Hospital, New Zealand |
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| Abstract: | IntroductionPerinatal 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.MethodsFA 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.ResultsIL-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.DiscussionDepleted 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. |
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| Keywords: | Asphyxia Fetal Inflammation Placenta Preconditioning |
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