Fetal alcohol spectrum disorder: pathogenesis and mechanisms.

This chapter provides an overview of animal model-based studies that have generated information critical to our understanding of the pathogenesis and mechanisms underlying alcohol-induced birth defects, in particular those involving the brain. Focus is placed on the developing organism itself, rather than the mother, placenta, or other extraembryonic tissues. Components of the cascades of alcohol-induced damage that are considered herein are excessive cell death, changes in the cell cycle and proliferation, cell migration, cell morphogenesis, and gene expression as well as free radical damage and interference with cell signaling. The roles played by one or more of these various factors in the genesis of structural and functional birth defects are dependent upon alcohol exposure patterns and dosage, the involved tissue, and the prenatal stage(s) at the time of exposure. Technologic advances and rapidly increasing knowledge in the fields of genetics, cell, developmental, and neurobiology are critical to accurately piecing together experimental evidence in refining our understanding of the genesis of alcohol-induced birth defects, to the planning and execution of future studies, and to applying the knowledge gained to diminish the severity or occurrence of fetal alcohol spectrum disorder.