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BOR - Papers in Press, published online ahead of print December 11, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.009688
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BIOLOGY OF REPRODUCTION 68, 1695–1702 (2003)
DOI: 10.1095/biolreprod.102.009688
© 2003 by the Society for the Study of Reproduction, Inc.


Pregnancy

Fetal Responses to Maternal and Intra-Amniotic Lipopolysaccharide Administration in Sheep1

Peta L. Grigsby3, Jonathan J. Hirst2,3, Jean-Pierre Scheerlinck4, David J. Phillips5, and Graham Jenkin3,5

Fetal and Neonatal Research Group,3 Department of Physiology, Monash University, Clayton, Victoria 3800, Australia Centre for Biotechnology,4 University of Melbourne, Melbourne, Victoria 3052, Australia Institute of Reproduction and Development,5 Monash Medical Centre, Clayton, Victoria 3168, Australia

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.

1 Supported by a Program Grant from the National Health & Medical Research Council of Australia.

2 Correspondence: Jonathan Hirst, Department of Physiology, 13F Monash University, Wellington Road, Clayton, Victoria 3800, Australia. FAX: 613 9905 2547; jon.hirst{at}med.monash.edu.au




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