Cardiac mitochondrial abnormalities in a mouse model of the fetal alcohol syndrome.
Mitochondrial enzymes and respiration were studied in the hearts of mice exposed to ethanol in utero from gestational Day 8 to parturition. This treatment had previously been shown by electron microscopy to result in myofibril loss and mitochondrial abnormalities. Ethanol was administered to pregnant mice by a liquid diet paradigm and pair-fed dams were used as controls. Ethanol exposure in utero reduced the activities of two mitochondrial inner membrane enzymes, cytochrome c oxidase and succinate dehydrogenase, in the hearts of perinatal mice. Secondly, mitochondrial respiration under both State 3 and 4 conditions with a NAD-linked substrate was depressed in the hearts obtained from the ethanol-exposed fetal mice. However, when a flavin-linked substrate was used, State 3 (ADP-stimulated) but not State 4 respiration was depressed. This study illustrates that in utero exposure to ethanol is deleterious to the functioning of cardiac mitochondria in newborn mice, which in turn could contribute to the development of the heart pathologies present in the Fetal Alcohol Syndrome.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008293:Malates / Q000378:metabolism; D051379:Mice; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D005971:Glutamates; D008293:Malates; D013386:Succinates; D009243:NAD; D000431:Ethanol; D018698:Glutamic Acid; C030298:malic acid; D019802:Succinic Acid; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV