title: Retinoic acid reverses ethanol-induced cardiovascular abnormalities in quail embryos.
abstract: 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.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224, USA.
authors.forename: W O
authors.initials: WO
authors.lastname: Twal
authors.forename: M H
authors.initials: MH
authors.lastname: Zile
mesh_terms: 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
chemical_list: D000431:Ethanol; D014212:Tretinoin