Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome.
Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome (e.g., craniofacial changes and growth restriction in adolescent mice). In this study, we characterize in detail the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and by extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of nonfostered, ethanol-exposed and control mice at postnatal day 28.We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This finding suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiologic result of ethanol exposure in utero. We also find that, despite some catch-up growth after 5 weeks of age, the effect extends into adulthood, which is consistent with longitudinal studies in humans.Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis, and lipid metabolism.
Kaminen-Ahola
Nina
N
Epigenetics Laboratory, Queensland Institute of Medical Research, 300 Herston Rd., Herston, Queensland 4006, Australia.
Ahola
Arttu
A
Flatscher-Bader
Traute
T
Wilkins
Sarah J
SJ
Anderson
Greg J
GJ
Whitelaw
Emma
E
Chong
Suyinn
S
D000818:Animals; D001835:Body Weight; D019465:Craniofacial Abnormalities / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011247:Pregnancy
D000431:Ethanol