Effect of Ethanol on Development of Fetal Mouse Thymocytes in Organ Culture

Exposure of mouse fetuses to ethanol in utero retards thymus development. The direct effect of ethanol on growth and differentiation of thymocytes was studied using organ cultures of 14-day fetal mouse thymuses. Fetal thymus organ cultures containing 0.2 or 0.4% ethanol produced fewer total thymocytes, proportionately fewer CD4+CD8+ (immature) thymocytes, and proportionately more CD4+CD8- (mature) cells than untreated control cultures after 5 days of culture. Total cell numbers and proportions of CD4+CD8+ thymocytes declined in a dose-dependent manner with increasing ethanol concentrations from 0.2 to 0.8%. In time course studies, thymuses cultured with 0.4% ethanol had an increased percentage of CD4+CD8- cells at all days examined between Days 4 and 6. In the same experiments, thymuses exposed to ethanol underwent accelerated loss of the interleukin-2 receptor (a marker of immature prothymocytes) and had higher percentages of cells positive for the γδ-T-cell receptor. Exposure to ethanol for 16 to 20 hr increased the percentage of noncycling thymocytes. Furthermore, ethanol increased apoptosis in fetal thymocytes. Acetaldehyde, the immediate product of ethanol catabolism, had no effect on thymocyte sub-population ratios or cell numbers at a physiologic concentration (50 μM Results indicate that in a controlled in vitro model of thymus development, ethanol reduced cell numbers and altered proportions of thymocyte subsets defined by differentiation antigens.