Exposure to systemic and intrauterine inflammation leads to decreased pup survival via different placental mechanisms

Ji Yeon Lee, Na E. Shin, Quan Na, Jie Dong, Anna Chudnovets, Su Li, Christopher M. Novak, Michael W. McLane, Jun Lei, I. Burd

Research output: Contribution to journalArticlepeer-review

Abstract

Problem: Exposure to systemic maternal inflammation (i.e., maternal sepsis, influenza, human immunodeficiency virus, or pyelonephritis) and intrauterine (IU) inflammation (i.e., chorioamnionitis or preterm labor) have been associated with adverse perinatal sequelae. Whether systemic and localized inflammation leading to adverse outcomes have similar placental mechanisms remain unclear. Method of Study: We conducted a study by murine modeling systemic and localized IU inflammation with injections of either intraperitoneal (IP) or IU interleukin-1β (IL-1β) and compared fetoplacental hemodynamic changes, cytokine/chemokine expression, and fetal loss. Results: IU IL-1β exposure reduced offspring survival by 31.1% and IP IL-1β exposure by 34.5% when compared with control pups. Despite this similar outcome in offspring survival, Doppler analysis revealed a stark difference: IU group displayed worsened fetoplacental hemodynamic changes while no differences were found between IP and control groups. While both IU and IP groups had increases in pro-inflammatory cytokines and chemokines, specific gene expression trends differed between the two groups, once again highlighting their mechanistic differences. Conclusion: While both IP and IU IL-1β exposure similarly affected pup survival, only IU inflammation resulted in fetoplacental hemodynamic changes. We speculate that exposure to maternal systemic and IU inflammation plays a key role in fetal injury by utilizing different placental inflammatory pathways and mechanisms.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalJournal of Reproductive Immunology
Volume133
DOIs
StatePublished - Jun 2019

Keywords

  • Doppler waveform
  • Intrauterine inflammation
  • Maternal inflammation
  • Mice
  • Placenta
  • interleukin-1β

ASJC Scopus subject areas

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

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