Retinoic acid reverses ethanol-induced cardiovascular abnormalities in quail embryos.
The effect of ethanol on early avian cardiovascular development was investigated in stage 8 quail embryos grown in culture for 24 hr. When the culture medium contained 1% ethanol, 50% of the embryos developed abnormalities of the cardiovascular system, some of which resembled vitamin A deficiency. Only 15% of the embryos grown in control media developed abnormalities attributed to the manipulation of the embryo. When all-trans-retinoic acid, the active form of vitamin A, was added at 10(-8) M to the ethanol-containing medium, the cardiovascular development was similar to that of untreated controls. Inclusion of 4-methylpyrazole and citral, enzyme inhibitors for the conversion of retinol to retinoic acid, produced cardiovascular abnormalities in embryos similar to those observed in vitamin A deficiency. These abnormalities were partially prevented by the presence of 10(-8) M all-trans-retinoic acid in the medium. Immunohistochemical studies using antibodies specific for the heart muscle myosin heavy chain (MF-20) and quail endothelial cells (QH-1) revealed that looping of the heart of ethanol-treated embryos was prevented, and the embryonal circulation had no or minimal vascular connections to the extraembryonic circulation. Our studies provide indirect evidence that ethanol is producing vitamin A deficiency during embryonic cardiovascular development and that these effects are specifically prevented by the presence of retinoic acid. These findings may explain some of the symptoms of fetal alcohol syndrome.
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Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224, USA.
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D063647:Fetal Alcohol Spectrum Disorders / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology*; D011784:Quail; D014212:Tretinoin / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000196:embryology
D000431:Ethanol; D014212:Tretinoin