Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth restriction and enhances pulmonary function in a newborn mouse model of perinatal inflammation.
The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothesis that DHA supplementation to the dam would reduce hyperoxic lung injury and growth deficits in a more severe model of systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg diet) or control diets and injected with saline or LPS. Diets were maintained through weaning. At birth, pups were placed in room air or hyperoxia for 14 d. Improvements in birth weight (P < 0.01), alveolarization (P ≤ 0.01), and pulmonary function (P ≤ 0.03) at 2 and 8 wk of age were observed in pups exposed to perinatal inflammation and born to DHA-supplemented dams compared with control diet-exposed pups. These improvements were associated with decreases in tissue macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P ≤ 0.05), and decreases in soluble receptor for advanced glycation end products concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation attenuated pulmonary fibrosis, which was associated with the reduction of matrix metalloproteinases 2, 3, and 8 (P ≤ 0.03) and collagen mRNA (P ≤ 0.05), and decreased collagen (P < 0.01) and vimentin (P ≤ 0.03) protein concentrations. In a model of severe inflammation, maternal DHA supplementation lessened inflammation and improved lung growth in the offspring. Maternal supplementation with DHA may be a therapeutic strategy to reduce neonatal inflammation.
Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH.
Markus
M
Velten
Rodney D
RD
Britt
Kathryn M
KM
Heyob
Trent E
TE
Tipple
Lynette K
LK
Rogers
D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D018932:Chemokine CCL2 / Q000378:metabolism; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000188:drug therapy*; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D018496:Hyperoxia / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D004281:Docosahexaenoic Acids; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse