Magnetic Resonance Microscopy-based Analyses of the Brains of Normal and Ethanol-exposed Fetal Mice

Background: The application of magnetic resonance microscopy (MRM) to the study of normal and abnormal prenatal mouse development has facilitated discovery of dysmorphology following prenatal ethanol insult. The current analyses extend this work, providing a regional brain volume-based description of normal brain growth and illustrating the consequences of gestational day (GD) 10 ethanol exposure in the fetal mouse.

Methods: To assess normal growth, control C57Bl/6J fetuses collected on GD 16, GD 16.5, and GD 17 were scanned using a 9.4-T magnet, resulting in 29-μm isotropic resolution images. For the ethanol teratogenicity studies, C57Bl/6J dams were administered intraperitoneal ethanol (2.9 g/kg) at 10 days, 0 hr, and 10 days, 4 hr, after fertilization, and fetuses were collected for analyses on GD 17. From individual MRM scans, linear measurements and regional brain volumes were determined and compared.

Results: In control fetuses, each of the assessed brain regions increased in volume, whereas ventricular volumes decreased between GD 16 and GD 17. Illustrating a global developmental delay, prenatal ethanol exposure resulted in reduced body volumes, crown-rump lengths, and a generalized decrease in regional brain volumes compared with GD 17 controls. However, compared with GD 16.5, morphologically matched controls, ethanol exposure resulted in volume increases in the lateral and third ventricles as well as a disproportionate reduction in cortical volume.

Conclusions: The normative data collected in this study facilitate the distinction between GD 10 ethanol-induced developmental delay and frank dysmorphology. This work illustrates the utility of MRM-based analyses for developmental toxicology studies and extends our knowledge of the stage-dependency of ethanol teratogenesis.