ResearchBasic science: ObstetricsFetal alcohol syndrome: cardiac birth defects in mice and prevention with folate
Section snippets
Avian model
White leghorn chick (Gallus gallus; Charles River Laboratories, Wilmington, MA) and quail (Coturnix coturnix; Strickland Farms, Lake Park, GA) embryos were used because of accessibility to determine precisely the embryonic stage. Heart development in the avian embryo is similar to that in the mouse and human. Stage 4 embryos10 were incubated on an agar-albumin medium for 8 or 24 hours at 38°C.11 The teratogenic ethanol dose was determined to be 25-30% ethanol. Control embryos were incubated on
Alcohol exposure of avian embryos during gastrulation
Avian embryos that were exposed to ethanol in vitro at Hamburger and Hamilton staging10 stage 4 displayed morphologic defects of delayed growth and severe cardiac malformations (Figure 1, A, control, and B-D, ethanol exposed; Figure 2). After 24 hours, the early cardiac malformations included (1) wide hearts at embryonic middle and cardia bifida (ie, bilateral heart fields not fusing, (2) cardiac tissue situated anterior to the head that signified a truncation of the neural tube because of an
Comment
The mouse and avian results, when taken together, suggest that acute ethanol exposure potentiates Wnt/β-catenin inhibition of early cardiogenesis by suppressing expression of 2 cardiac-inducing molecules, Hex and Islet 1.21, 22 These genes are activated when canonical Wnt signaling is inhibited by Wnt antagonists. We demonstrated that high dietary folate taken from the time of conception can prevent the alcohol-induced heart defects. These results support a recent Canadian epidemiologic human
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Reprints not available from the authors.
Supported in part by the Mason Chair Endowment (K.K.L.) from the Foundation of the University of South Florida College of Medicine and All Children's Hospital.
Cite this article as: Serrano M, Han M, Brinez P, et al. Fetal alcohol syndrome: cardiac birth defects in mice and prevention with folate. Am J Obstet Gynecol 2010;203:75.e7-15.