Genetic influences on craniofacial outcome in an avian model of prenatal alcohol exposure.
BACKGROUND
Understanding the basis for ethanol's teratogenic effects may inform the etiology of fetal alcohol syndrome. Here we investigate how genetic background and susceptibility to ethanol-induced neural crest apoptosis contribute to the distinctive craniofacial phenotype observed after prenatal alcohol exposure.


METHODS
Nine different chick strains were exposed to ethanol at gastrulation. The sensitivity of these embryos to ethanol-induced neural crest apoptosis was reported elsewhere (Debelak and Smith, 2000). Here, these embryos were permitted to develop until embryonic day 10, when facial morphogenesis was largely complete, and cephalometric measurements were made on cleared skulls. Shifts in facial growth were correlated against the severity of ethanol-induced apoptosis in facial precursors.


RESULTS
The facial shape produced by ethanol exposure was a function of the embryos' genetic strain. Three general responses were observed: apparent midfacial flattening (Babcock B300 x Hampshire Red, ISA-Babcock, HyLine W98, and HyLine W36 strains), overall facial expansion (Spafas and Babcock B300 strains), or overall facial hypoplasia (DeKalb strains). When dose and timing of exposure were held constant, the embryo's genetic background predicted the facial outcome. For ethanol-sensitive strains, apoptosis of facial precursor populations was required to produce the facial defects. That some strains had essentially normal faces despite extensive cell death indicated a capacity to recover from the earlier neural crest losses.


CONCLUSIONS
We propose that ethanol's effects on craniofacial development are multifactoral, and these influences may include susceptibility to apoptosis, regenerative capacity, and compensatory outgrowth of the facial primordia. The embryo's genetic background may modulate these events. The high and low responder chick strains are useful tools to dissect these contributions.
Su
B
B
Department of Nutritional Sciences and Graduate Program in Environmental Toxicology, University of Wisconsin-Madison, 53706, USA.
Debelak
K A
KA
Tessmer
L L
LL
Cartwright
M M
MM
Smith
S M
SM
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D002645:Chickens; D019465:Craniofacial Abnormalities / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D009432:Neural Crest / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013045:Species Specificity
D002492:Central Nervous System Depressants; D000431:Ethanol