title: Hindbrain and cranial nerve dysmorphogenesis result from acute maternal ethanol administration.
abstract: Acute exposure of mouse embryos to ethanol during stages of hindbrain segmentation results in excessive cell death in specific cell populations. This study details the ethanol-induced cell loss and defines the subsequent effects of this early insult on rhombomere and cranial nerve development. Ethanol at a teratogenic dosage (2.9 g/kg) or a comparable volume of vehicle was administered in each of two intraperitoneal injections to pregnant C57BL/6J mice on gestational day (GD) 8, 8 h, and GD 8, 12 h (defined hereafter as GD 8.5). Ethanol-exposed GD 9 embryos, visualized in three dimensions using laser scanning confocal microscopy of LysoTracker Red fluorescence or Nile blue sulphate vital staining, displayed excessive apoptosis in the rostral hindbrain, specifically within rhombomeres 1-3, as well as in cranial neural crest cells and ectodermal placodes. Comparably treated embryos examined on GD 10.5-11 illustrated a disproportionate reduction in the length of the rostral hindbrain. Examination of plastic histological sections of GD 9 embryos and via scanning electron microscopy on GD 10 revealed deficiencies in the hindbrain, with a phenotype including abnormal rhombomere segmentation and an extremely small fourth ventricular roofplate. Whole-mount antineurofilament immunohistochemistry on GD 10.5 and GD 11 illustrated a variety of cranial nerve abnormalities ranging from fused or absent ganglia to ectopic or disorganized fibers. In addition, a delay in the development of the glossopharyngeal (IX) nerve/ganglia complex was observed. These hindbrain and cranial nerve abnormalities are discussed in the context of the genesis of human alcohol-related birth defects and neurodevelopmental disorder.
authors.affiliation: Department of Cell and Developmental Biology and the Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC 27599-7090, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Dunty
authors.forename: Robert M
authors.initials: RM
authors.lastname: Zucker
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Sulik
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D003391:Cranial Nerves / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D016900:Neurofilament Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012249:Rhombencephalon / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D016900:Neurofilament Proteins; D000431:Ethanol