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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2009-03, Vol.296 (3), p.L510-L518
• Main Authors: Sozo, Foula, O'Day, Luke, Maritz, Gert, Kenna, Kelly, Stacy, Victoria, Brew, Nadine, Walker, David, Bocking, Alan, Brien, James, Harding, Richard
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cells; Collagen - metabolism; Collagen Type I - genetics; Cytokines; Cytokines - genetics; DNA Primers - genetics; Elastin - metabolism; Ethanol; Ethanol - administration & dosage; Ethanol - toxicity; Female; Fetal Organ Maturity - drug effects; Fetal Organ Maturity - genetics; Fetal Organ Maturity - immunology; Fetus - drug effects; Fetus - immunology; Fetuses; Gene Expression - drug effects; Immunity, Innate - drug effects; Immunity, Innate - genetics; Inflammation Mediators - metabolism; Lung - drug effects; Lung - embryology; Lung - immunology; Lung - metabolism; Lungs; Maternal-Fetal Exchange - immunology; Oxidation; Oxidative Stress; Pregnancy; Proteins; Pulmonary Surfactant-Associated Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sheep
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.90532.2008

1 Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia; 2 Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa; 3 Department of Physiology, Monash University, Melbourne, Victoria, Australia; 4 Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada; and 5 Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada Submitted 22 October 2008 ; accepted in final form 19 December 2008 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 147 days). From 95-133 DGA, ewes were given a 1-h 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 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 proinflammatory cytokines interleukin (IL)-1β and IL-8 were also lower ( P < 0.05) in ethanol-exposed fetuses compared with 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. lung growth; lung morphometry; surfactant proteins; proinflammatory cytokines Address for reprint requests and other correspondence: F. Sozo, Dept. of Anatomy and Developmental Biology, P.O. Box 13C, Monash Univ., Melbourne, VIC 3800, Aus