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Genetic factors influence adverse pregnancy outcome in both humans and animal models. Animal research reveals both the maternal and fetal genetic profiles are important for determining the risk of physical birth defects and prenatal mortality. Using a reciprocal-cross breeding design, we investigated whether the mother’s genes may be more important than fetal genes in determining risk for ethanol teratogenesis. Examination of possible synergistic genetic effects on ethanol teratogenesis was made possible by using two mouse strains known to be susceptible to specific malformations. Inbred A/J (A) and C57BL/6J (B6) mice were mated to produce four fetal genotype groups: the true-bred A∙A and B6∙B6 genotypes and the genetically identical A∙B6 and B6∙A genotypes (the F1 genotype). Dams were administered either 5.8 g/kg ethanol or an isocaloric amount of maltose-dextrin on day 9 of pregnancy. Fetuses were removed by laparotomy on gestation day 18, weighed, and assessed for digit, vertebral, and kidney malformations. Digit malformations in the genetically identical F1 ethanol-exposed litters showed a pattern consistent with a maternal genetic effect [A∙B6 (2%) and B6∙A (30%)]. In contrast, vertebral malformations were similar in all ethanol-exposed litters [A∙A (26%), A∙B6 (18%), B6∙A (22%), and B6∙B6 (33%)]. The percentage of malformations did not differ between male and female fetuses, indicating sex-linked factors are not responsible for the maternal effect. Ethanol exposure decreased litter weights but did not affect litter mortality compared to maltoseexposed controls. This study supports the idea that genes influence malformation risk following in utero alcohol exposure. Specifically, maternal genes influence risk more than fetal genes for some teratogenic outcomes. No evidence supported synergistic genetic effects on ethanol teratogenesis. This research supports the conclusion that uterine environment contributes to determining risk of Fetal Alcohol Spectrum Disorder.

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DOI: 10.1016/j.alcohol.2011.02.308


Fetal Alcohol Syndrome; Genetics; Extra-chromosomal inheritance; Inbred mice

Place of Publication

United States

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Copyright is held by the publisher. See Notes for more information.


NOTICE: This is the author’s version of a work that was accepted for publication in Alcohol. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Alcohol, [Volume 45, Issue 5, (August 2011)] DOI: 10.1016/j.alcohol.2011.02.308


24 pages (in manuscript)

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