Adverse effects of maternal alcohol consumption during pregnancy include the immune-deficiencies reported in children with fetal alcohol syndrome. Animal models have also shown that fetal alcohol exposure (FAE) produces T-cell-specific immunosuppression that likely arises from altered thymic development. In the investigator model, this T-cell dysfunction is prevalent in the male FAE offspring. The prevalence of relative immune-deficiency in males in general makes this model appropriate and clinically significant. The investigator's overall hypothesis is that the male-specific T cell dysfunction likely originates in altered thymic development due to elevated maternal corticosterone during a critical period followed by the prenatal surge of testosterone on the fetal male thymus. Their original observation that maternal adrenalectomy (ADX) reverses to T-cell dysfunction in the male FAE offspring, but induces a T-cell dysfunction in the FAE female, suggests that maternal adrenal factors, in addition to alcohol, are involved in these effects. Maternal ADX eliminates maternal plasma CORT, the newly identified surge of maternal plasma dehydroepiandrosterone (DHEA), and attenuates the prenatal surge of plasma testosterone (T) in the male fetus. Thus, some of these steroids may disrupt developmental processes in the male, but protect the female fetal thymus in the presence of alcohol. Therefore, this proposal seeks to determine whether: 1.) the T-cell dysfunction observed in the male FAE offspring is solely due to elevated maternal CORT levels, and what is the critical period of exposure; 2.) inhibiting the maternal CORT response to alcohol in the intact pregnant rat will attenuate the immunosuppressive effects of FAE; 3.) the surge of maternal DHEA contributes to the protection of the FAE female fetal thymus; 4.) the thymolytic characteristics of T-cells contribute to the increased susceptibility to FAE in the male fetus; and 5.) these steroids affect directly the production of specific cytokines by fetal thymic epithelial cells in culture. The results of these studies could contribute to our understanding of the mechanism of FAE-induced immune-deficiency, and in a broader context, the male predominance in the incidence of infectious diseases in children.
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| Redei, E; Halasz, I; Li, L F et al. (1993) Maternal adrenalectomy alters the immune and endocrine functions of fetal alcohol-exposed male offspring. Endocrinology 133:452-60 |
| Redei, E (1992) Immuno-reactive and bioactive corticotropin-releasing factor in rat thymus. Neuroendocrinology 55:115-8 |
