Thymic Morphology and Increased Apoptotic Rates in Juvenile and Adult Female Mice Following Exposure to Low Levels of Arsenic Early in Development

The children of mothers who drank arsenic-contaminated water during pregnancy have been found to have higher morbidity and mortality due to infection compared to children that were not exposed. In both human and mouse studies, these offspring have been found to have smaller thymi and lesser maturation of immature thymocytes into mature T cells, which are key components of the cell-mediated immune response. In the present study, dams were exposed to 0, 50, or 500ppb sodium arsenite in their drinking water during pregnancy and weaning, and the thymi of the offspring were collected at either PND 21 (prepubescent) or 5 MO (sexually mature adult). Morphological differences were assessed via light microscopy of hematoxylin and eosin stained coronal thin sections of paraffin-embedded thymi. Differences in the density of apoptotic cells were assessed via light microscopy of coronal thin sections of thymi stained via colorimetric TUNEL assay. Because the thymus undergoes significant morphological changes with age, effects of arsenic exposure had to be distinguished from the natural effects of age. Results indicated that there was no significant effect of arsenic exposure on the morphology of the mouse thymus, at both ages. However, there was an approximately two-fold increase in the density of apoptotic cells in both the thymic cortex and medulla at both exposure levels (two-way ANOVA; p = 0.0131 and 0.0030, respectively; n = 3-5), which could result in fewer mature T cells reaching the peripheral lymphoid tissues and contributing to the immune response.