Bacterial lipopolysaccharide-mediated fetal death: Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide

Robert M. Silver, Samuel S. Edwin, Michael S. Trautman, Daniel L. Simmons, D. Ware Branch, Donald J. Dudley, Murray D. Mitchell

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 μg of LPS. Also, decidual explants from LPS-treated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death.

Original languageEnglish (US)
Pages (from-to)725-731
Number of pages7
JournalJournal of Clinical Investigation
Volume95
Issue number2
DOIs
StatePublished - Feb 1995
Externally publishedYes

Keywords

  • Cyclooxygenase
  • Fetal death
  • Infection
  • Pregnancy
  • Prostaglandin

ASJC Scopus subject areas

  • Medicine(all)

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