Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep

Peta L. Grigsby, Jonathan J. Hirst, Jean Pierre Scheerlinck, David J. Phillips, Graham Jenkin

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


A link between intrauterine infection and premature labor is widely accepted, yet the fetal inflammatory responses to such infections are not well understood. Our aim was to use a sheep model in which an inflammatory state was induced by lipopoly-saccharide (LPS) administration during pregnancy to the maternal systemic, intra-amniotic or extra-amniotic compartments. Fetal and maternal blood gases and uterine electromyographic activity along with fetal and maternal circulating concentrations of prostaglandins PGE2 and PGFM, cortisol, and interleukin-6 were determined. Maternal systemic LPS treatment resulted in mild maternal hypoxemia, a rise in temperature, greater fetal hypoxemia, and a marked rise in fetal cortisol and PGE2 concentrations that persisted for 48 h. Intra-amniotic administration of LPS at doses higher than those used systemically caused an increase in fetal cortisol and PGE2 concentrations as well as a rise in uterine activity, but these were lesser in magnitude. Extraamniotic LPS administration caused no overt fetal or maternal inflammatory responses. We conclude that maternal LPS treatment markedly elevated fetal cortisol and PGE2 concentrations. This may be a potential protective mechanism that aids the fetus in the event of premature delivery. The attenuated fetal response to intra-amniotic LPS treatment, despite the much higher dose used, may support a role for the amniotic fluid in protecting the fetus from endotoxin exposure during pregnancy.

Original languageEnglish (US)
Pages (from-to)1695-1702
Number of pages8
JournalBiology of reproduction
Issue number5
StatePublished - May 1 2003
Externally publishedYes


  • Cortisol
  • Cytokines
  • Parturition
  • Placenta
  • Uterus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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