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. doi: 10.1111/acer.12464. Epub 2014 Jun 13.


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.

Keywords: Brain; Ethanol; Fetal Alcohol Spectrum Disorder; Magnetic Resonance Microscopy; Mouse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Drug-Induced / diagnosis
  • Abnormalities, Drug-Induced / pathology*
  • Animals
  • Brain / abnormalities*
  • Brain / drug effects*
  • Ethanol / toxicity*
  • Female
  • Hydrops Fetalis / chemically induced
  • Hydrops Fetalis / pathology
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Neuroimaging
  • Pituitary Gland / abnormalities
  • Pregnancy
  • Pregnancy Trimester, First* / drug effects


  • Ethanol