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Dysmorphogenic Effects of First Trimester-Equivalent Ethanol Exposure in Mice: A Magnetic Resonance Microscopy-Based Study

Institution:
1Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC,USA.
2Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC,USA.
Publisher:
Blackwell Publishing
Publication Date:
Jul-2014
Journal:
Alcohol Clin Exp Res
Volume Number:
38
Issue Number:
7
Pages:
2008-14
Citation:
Alcohol Clin Exp Res. 2014 Jul;38(7):2008-14.
PubMed ID:
24931007
PMCID:
PMC4107075
Keywords:
Brain, Ethanol, Fetal Alcohol Spectrum Disorder, Mouse, Magnetic Resonance Microscopy
Appears in Collections:
NA-MIC
Sponsors:
K99 AA018697/AA/NIAAA NIH HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
P41 EB015897/EB/NIBIB NIH HHS/United States
U01 AA017124/AA/NIAAA NIH HHS/United States
U01 AA021651/AA/NIAAA NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
Generated Citation:
Parnell S.E., Holloway H.E., Baker L.K., Styner M.A., Sulik K.K. Dysmorphogenic Effects of First Trimester-Equivalent Ethanol Exposure in Mice: A Magnetic Resonance Microscopy-Based Study. Alcohol Clin Exp Res. 2014 Jul;38(7):2008-14. PMID: 24931007. PMCID: PMC4107075.
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BACKGROUND: The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution magnetic resonance microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods. METHODS: Female C57Bl/6J mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while on standard chow. Dams were again provided the EtOH-containing liquid diet for a period that extended either from the beginning of gestational day (GD) 7 to the end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a subset of fetuses was selected for MRM-based analyses. Group comparisons were made for litter characteristics and gross dysmorphology, as well as whole and regional brain volumes. RESULTS: EtOH-induced stage of exposure-dependent structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group presented with a significant decrease in cerebellar volume and an increase in septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12 to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. CONCLUSIONS: These results illustrate the teratogenic impact of maternal dietary EtOH intake occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to 11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation, further documenting EtOH's stage of exposure-dependent neuroteratogenic end points and highlighting the vulnerability of selected brain regions during the first trimester. Additionally they suggest that clinical attention should be paid to fetal hydrops as a likely component of FASD.

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