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Pediatr Res. 2014 Apr;75(4):500-6. doi: 10.1038/pr.2014.3. Epub 2014 Jan 17.

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances.

Author information

1
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
2
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
3
1] School of Women's and Infants Health, University of Western Australia, Perth, Australia [2] Department of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
4
1] Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands [2] School of Women's and Infants Health, University of Western Australia, Perth, Australia.

Abstract

BACKGROUND:

Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero.

METHODS:

Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, Toll-like receptor (TLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated.

RESULTS:

After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and TLR1 at 125 d GA and (ii) monocytes, lymphocytes, TLR2, and TLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and TLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and TLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, TLR4, and TLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure.

CONCLUSION:

The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.

PMID:
24441106
DOI:
10.1038/pr.2014.3
[Indexed for MEDLINE]
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