Abnormal heart and great vessel development following acute ethanol exposure in mice.
Two maternal intraperitoneal doses of ethanol (2.9 g/kg) administered on gestational day (GD) 8, 12 hours (8 d, 12 h) and 8 d, 16 h result in abnormal heart and great vessel development in C57B1/6J mice. Heparinized hearts from GD 9 to 18 conceptuses were dissected to expose the forming or already completed ventricular septum and great vessels and then routinely processed for scanning electron microscopy. As early as GD 9 (12 hours post-treatment), size deficiency and abnormal external contour of the cardiac tube were notable. By GD 12, deficiencies in the size of the conal and atrioventricular (A-V) endocardial cushions, as well as abnormal positioning of the A-V canal, were demonstrable. On GD 13, when the ventricular septum should be complete, a range of deficiencies in the conal tissue was observed. Deficiencies observed were a lack of closure of the ventricular septum in the region of the membranous septum, and lack of septation of the conal portion of the developing heart. These deficiencies persist and have been documented through GD 18. Other abnormalities noted on GD 18 include double-outlet right ventricle, as well as distal defects of the great vessels including interrupted aortic arch, right aortic arch, and a vascular ring. While these defects are comparable to those seen in the fetal alcohol syndrome, they also overlap considerably with cardiac defects that are characteristic of those in the DiGeorge Syndrome as well as in the CHARGE Association. Recent work by others as well as the fact that acute ethanol exposure in this animal model corresponds to a time of neural crest cell migration has led to the speculation that this cell population is involved in the cardiovascular pathogenesis described.
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D018376:Cardiovascular Abnormalities; D002319:Cardiovascular System / Q000187:drug effects / Q000648:ultrastructure; D020964:Embryo Loss / Q000139:chemically induced; D005314:Embryonic and Fetal Development / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy
D000431:Ethanol