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

Background: Previous studies have demonstrated that excessive prenatal alco hol exposure can damage the auditory and vestibular systems, in particular, cochlear hair cells. However, the direct effect of ethanol on the peripher al neurons in these pathways has not been examined. To study the effects of prenatal ethanol exposure on the developing vestibulocochlear ganglion (VC G) complex and the peripheral sensory organs, we exposed pregnant mice to e thanol and examined the levels of cell death in the inner ear. Methods: Pregnant C57BL/6J mice were administered one of three doses of eit her ethanol (3.0, 4.5, and 5.5 g/kg) or isocaloric maltose/dextrin via intr agastric intubation on gestational day (GD) 1.2.5. Embryos were dissected o ut of the uterus 8 hr after the intubation. Dying cells in the inner ear we re stained with Nissl stain and labeled by in situ terminal dUTP nick-end l abeling (TUNEL), and the percentage of dying cells was quantified. Results: Ethanol exposure produced region-specific effects, with ethanol-ex posed embryos exhibiting enhanced cell death only in the VCG complex, and n ot in the primitive saccule, cochlea, semicircular canal, or endolymphatic sac. The effects of ethanol on cell death in the VCG are dose dependent, wi th a significant increase in the level of cell death found only at the high er doses. Conclusions: Ethanol has a selective cytotoxic dose-dependent effect on the VCG at GD 12.5 suggesting that loss of VCG neurons may contribute to heari ng and/or vestibular abnormalities in FAS children. Furthermore, the presen ce of TUNEL-positive cells and DNA laddering is consistent with the cells u ndergoing apoptotic cell death. (C) 2001 Wiley-Liss, Inc.