Increased cell death in the developing vestibulocochlear ganglion complex of the mouse after prenatal ethanol exposure.

Abstract

Previous studies have demonstrated that excessive prenatal alcohol exposure can damage the auditory and vestibular systems, in particular, cochlear hair cells. However, the direct effect of ethanol on the peripheral neurons in these pathways has not been examined. To study the effects of prenatal ethanol exposure on the developing vestibulocochlear ganglion (VCG) complex and the peripheral sensory organs, we exposed pregnant mice to ethanol and examined the levels of cell death in the inner ear. Pregnant C57BL/6J mice were administered one of three doses of either ethanol (3.0, 4.5, and 5.5 g/kg) or isocaloric maltose/dextrin via intragastric intubation on gestational day (GD) 12.5. Embryos were dissected out of the uterus 8 hr after the intubation. Dying cells in the inner ear were stained with Nissl stain and labeled by in situ terminal dUTP nick-end labeling (TUNEL), and the percentage of dying cells was quantified. Ethanol exposure produced region-specific effects, with ethanol-exposed embryos exhibiting enhanced cell death only in the VCG complex, and not in the primitive saccule, cochlea, semicircular canal, or endolymphatic sac. The effects of ethanol on cell death in the VCG are dose dependent, with a significant increase in the level of cell death found only at the higher doses. Ethanol has a selective cytotoxic dose-dependent effect on the VCG at GD 12.5 suggesting that loss of VCG neurons may contribute to hearing and /or vestibular abnormalities in FAS children. Furthermore, the presence of TUNEL-positive cells and DNA laddering is consistent with the cells undergoing apoptotic cell death.