Inflammation-induced preterm birth in a murine model is associated with increases in fetal macrophages and circulating erythroid precursors

Linda M. Ernst, Juan Gonzalez, Ella Ofori, Michal Elovitz

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The presence of intrauterine inflammation has been associated with adverse neurologic outcomes in preterm infants, but the precise mechanisms of fetal brain injury remain unclear. We sought to evaluate inflammatory cell trafficking, fetal organ damage, and molecular regulation in the fetoplacental unit using an established mouse model of preterm birth associated with intrauterine inflammation. Gestational sacs were harvested 6 hours after intrauterine infusion of saline or lipopolysaccharide (LPS). Histologic, immunohistochemical, and molecular investigations were performed to identify target organ damage and the cellular phenotype of inflammatory cells and to quantify circulating inflammatory and hematopoietic mediators within the placental and fetal tissue. There was widespread increase in fetal macrophages in LPS-exposed pups, including within the leptomeninges of the brain, associated with significantly higher of interleukin 6 levels in LPS-exposed pups. Although no specific central nervous system injury (necrosis or apoptosis) was documented, liver hematomas were seen significantly more frequently in LPS-exposed pups. Circulating nucleated fetal erythrocytes were also present more frequently with LPS exposure without significantly higher erythropoietin levels than salineexposed mice. The presence of increased macrophages, increased circulating interleukin 6 levels, and increased circulating erythroid precursors in LPS-exposed pups suggests that these are significant factors associated with potential target organ damage, such as liver hematomas, associated with intrauterine inflammation and preterm birth. The role of macrophages within the fetal leptomeninges is unclear, but they may play an important role in inflammatory-mediated brain damage, and further investigation of their significance and potential as therapeutic targets is warranted.

Original languageEnglish (US)
Pages (from-to)273-281
Number of pages9
JournalPediatric and Developmental Pathology
Volume13
Issue number4
DOIs
StatePublished - Jul 2010

Keywords

  • Amniotic fluid infection
  • Fetal inflammation
  • Macrophage activation
  • Mouse model
  • Nucleated erythrocytes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

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