Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep.
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 lipopolysaccharide (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. Extra-amniotic 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.
Grigsby
Peta L
PL
Fetal and Neonatal Research Group, Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
Hirst
Jonathan J
JJ
Scheerlinck
Jean-Pierre
JP
Phillips
David J
DJ
Jenkin
Graham
G
D000653:Amniotic Fluid / Q000502:physiology*; D000818:Animals; D001784:Blood Gas Analysis; D015232:Dinoprostone / Q000378:metabolism; D004576:Electromyography; D004926:Escherichia coli / Q000737:chemistry; D005260:Female; D005333:Fetus / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D007267:Injections; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D007752:Obstetric Labor, Premature / Q000503:physiopathology; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011460:Prostaglandins F / Q000378:metabolism; D012756:Sheep; D014599:Uterus / Q000502:physiology
D015850:Interleukin-6; D008070:Lipopolysaccharides; D011460:Prostaglandins F; D015232:Dinoprostone; D006854:Hydrocortisone