Dose-dependent structural and immunological changes in the placenta and fetal brain in response to systemic inflammation during pregnancy

Anna Chudnovets, Jun Lei, Quan Na, Jie Dong, Harish Narasimhan, Sabra L. Klein, Irina Burd

Research output: Contribution to journalArticle

Abstract

Problem: Systemic maternal inflammation is associated with adverse neonatal sequelae. We tested the hypothesis that IL-1β is a key inflammatory regulator of adverse pregnancy outcomes. Method of study: Pregnant mice were treated with intraperitoneal injections of IL-1β (0, 0.1, 0.5, or 1 μg) from embryonic day (E)14 to E17. Placenta and fetal brains were harvested and analyzed for morphologic changes and IL-1β signaling markers. Results: As compared with non-treated dams, maternal injections with IL-1β resulted in increased p-NF-κB and caspase-1 in placentas and fetal brains, but not consistently in spleens, suggesting induction of intrinsic IL-1β production. These findings were confirmed by increased levels of IL-1β in the placentas of the IL-1β-treated dams. Systemic treatment of dams with IL-1β suppressed Stat1 signaling. Maternal inflammation caused by IL-1β treatment reduced fetal viability to 80.6% and 58.9%, in dams treated with either 0.5 or 1 μg of IL-1β, respectively. In the placentas, there was an IL-1β dose-dependent distortion of the labyrinth structure, decreased numbers of mononuclear trophoblast giant cells, and reduced proportions of endothelial cells as compared to placentas from control dams. In fetal brains collected at E17, there was an IL-1β dose-dependent reduction in cortical neuronal morphology. Conclusion: This work demonstrates that systemic IL-1β injection causes dose-dependent structural and functional changes in the placenta and fetal brain.

Original languageEnglish (US)
Article numbere13248
JournalAmerican Journal of Reproductive Immunology
Volume84
Issue number1
DOIs
StatePublished - Jul 1 2020

Keywords

  • IL-1β
  • maternal inflammation
  • perinatal brain injury
  • placenta

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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