Fetal Alcohol Syndrome (FAS) is a well recognized and important clinical neonatological entity with an incidence of 1-3/1000 births. Ethanol has a direct dose response to in utero mortality, low birth weight, soft tissue malformation and often, hypotonia, yet the mechanism or teratogenicity remains unknown. The syndrome is readily diagnosed when the infant presents with the characteristic phenotypic expression. However, less well characterized congenital anomalies may be attributable to lesser doses of ethanol exposure. The teratogenic effects of ethanol are predominantly organogenic and strongly implicate defect of cell movement possibly caused by structural protein maldevelopment. The purpose of this investigation is to attempt to delineate the mechanism of damage by studying myocyte embryogenesis and organogenesis during ethanol exposure. Preliminary data suggests that ethanol exerts its effect on muscle structural protein synthesis. In vitro cultures of developing myocytes will be examined to determine the exact nature of teratogenicity. The growth and development of myocyte structural proteins with emphasis on growth kinetics, structural and biochemical determinations of cellular activity, protein synthesis and degradation particularily of microfilaments) will be studied. Delineation of these structural protein alterations and associated biochemical abnormalities should provide a means to understand Fetal Alcohol Syndrome and Feta Alcohol Effects. Further studies will apply data from the in vitro observations to an animal model to determine if the in vitro effects are reproducible in vivo. Timing and dosage of ethanol exposure will be manipulated to assess tissue vulnerability. In separate experiments, female Sprague Dawley rats will be treated with ethanol during gestation during the specific embryogenesis- organogenesis period of heart and skeletal muscle development. Morphological and biochemical studies on muscles from rat pups exposed to ethanol will determine the degree and extent of teratogenesis. The long term objectives will be to correlate the findings in the muscle system to other embryogenic-organogenic events in the fetus which are also affected by ethanol, e.g., neuron migration, craniofacial development, etc.
| Adickes, E D; Mollner, T J; Lockwood, S K (1988) Closed chamber system for delivery of ethanol to cell cultures. Alcohol Alcohol 23:377-81 |
