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


CONCLUSIONS
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.
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Verena A
VA
Lambermont
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Elke
E
Kuypers
Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Jennifer J P
JJ
Collins
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
J Jane
JJ
Pillow
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
John P
JP
Newnham
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
Graeme R
GR
Polglase
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
Ilias
I
Nitsos
School of Women's and Infants Health, University of Western Australia, Perth, Australia.
Matthew W
MW
Kemp
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.
Alan H
AH
Jobe
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.
Suhas G
SG
Kallapur
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.
Boris W
BW
Kramer
D000818:Animals; D001835:Body Weight; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D009929:Organ Size; D011247:Pregnancy; D011270:Pregnancy, Animal; D012756:Sheep / Q000196:embryology*
D008070:Lipopolysaccharides