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Am J Physiol Lung Cell Mol Physiol (December 26, 2008). doi:10.1152/ajplung.90532.2008
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Submitted on October 22, 2008
Revised on December 5, 2008
Accepted on December 19, 2008

Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung

Foula Sozo1*, Luke O'Day1, Gert S Maritz2, Kelly Kenna1, Victoria Stacy1, Nadine Brew1, David W. Walker3, Alan D Bocking4, James F Brien5, and Richard Harding1

1 Monash University
2 University of the Western Cape
3 Monash University, School of Biomedical Sciences.
4 University of Toronto
5 Queen's University

* To whom correspondence should be addressed. E-mail: foula.sozo{at}med.monash.edu.au.

Little is known about the effects of fetal ethanol exposure on lung development. Our aim was to determine the effects of repeated ethanol exposure during late gestation on fetal lung growth, maturation and inflammatory status. Pregnant ewes were chronically catheterized at 91 days of gestational age (DGA; term ~147d). From 95-133 DGA, ewes were given a one hour daily infusion of either 0.75 g ethanol/kg (n=9) or saline (n=8), with tissue collection at 134 DGA. Fetal lungs were examined for changes in tissue growth, structure, maturation, inflammation and oxidative stress. Between treatment groups there were no differences in lung weight, DNA and protein contents, percent proliferating and apoptotic cells, tissue and air-space fractions, alveolar number and mean linear intercept, septal thickness, type-II cell number and elastin content. Ethanol exposure caused a 75% increase in pulmonary collagen I {alpha}1 mRNA levels (p<0.05) and a significant increase in collagen deposition. Surfactant protein (SP)-A and SP-B mRNA levels were approximately one third of control levels following ethanol exposure (p<0.05). The mRNA levels of the pro-inflammatory cytokines interleukin (IL)-1{beta} and IL-8 were also lower (p<0.05) in ethanol-exposed fetuses compared to controls. Pulmonary malondialdehyde levels tended to be increased (p=0.07) in ethanol-exposed fetuses. Daily exposure of the fetus to ethanol during the last third of gestation alters extracellular matrix deposition and surfactant protein gene expression, which could increase the risk of respiratory distress syndrome after birth. Changes to the innate immune status of the fetus could increase the susceptibility of the neonatal lungs to infection.







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