The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in mice.

Although toxicological and metabolic interactions of arsenic (As) and selenium (Se) have been suggested by epidemiolgical literatures, the past experimental studies mostly focused on acute, high-dose interaction, leaving the long-term, low-dose interaction unexplored. In the present study pregnant mice, fed either Se-deficient or adequate (0 or 5 micromol Se/kg diet, respectively) diet, were given oral gavage of sodium arsenite (0 or 58 micromol/kg per day; chosen as less than half of the fetotoxic dose in this protocol) from gestational day (GD) 7-16. The levels of As and Se as well as five selenoenzymes (glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and type-I, -II and -III iodothyronine deiodinases (DI-I, -II and -III) were examined on GD17 in the tissues of dams and of fetus. The Se-deficient mice showed significantly enhanced accumulation of As compared to the Se-adequate mice in maternal liver (increased by 48%) and fetal brain (by 31%). Although no direct evidence of the enhanced toxicity in the Se-deficient group was obtained, the As exposure affected the levels of Se and selenoenzymes, an effect which was more discernible in Se-deficient group. Although most of theses changes were mild or moderate, the DI-II activity in Se-deficient fetal brain showed a drastic four-fold increase by As exposure, suggesting a possible disturbance of thyroid hormone environment in the fetus. These data suggested that apparently non-toxic, in utero dose of As, showed enhanced accumulation when combined with Se-deficiency and could affect the metabolism/kinetics of Se in fetal brain, which might result in developmental toxicity in mice.