Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth

Placenta. 2016 Feb:38:84-92. doi: 10.1016/j.placenta.2015.12.016. Epub 2015 Dec 24.

Abstract

Introduction: 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.

Discussion: 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.

Keywords: Asphyxia; Fetal; Inflammation; Placenta; Preconditioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Asphyxia Neonatorum / etiology
  • Asphyxia Neonatorum / immunology
  • Asphyxia Neonatorum / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Fetal Hypoxia / immunology*
  • Fetal Hypoxia / metabolism
  • Fetal Hypoxia / pathology*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Ischemic Preconditioning*
  • Parturition / metabolism
  • Phenotype
  • Placenta / blood supply*
  • Placenta / immunology
  • Placenta / pathology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cytokines