Exposure to lead during critical windows of embryonic development: Differential immunotoxic outcome based on stage of exposure and gender

Previous rat studies with lead (Pb) have shown that exposure throughout the full gestational period results in persistent immunotoxicity detectable in both juvenile and adult offspring. en er differences are also evident. How ever, little is known about the persistent immunotoxic effects of Pb when a dministered during specific stages of embryonic development. Adult Sprague- Dawley female rats were administered Pb acetate (or control acetate) in the ir drinking water early in gestation (days 3-9) or late in gestation (days 15-21). Significantly depressed delayed type hypersensitivity (DTH) respons es as well as elevated IL-10 production, relative monocyte numbers, and inc reased relative thymic weights were observed in late-gestation Pb-exposed f emale offspring assessed as adults. In contrast, late-gestation Pb-treated male offspring had significantly increased IL-12 production and decreased I L-10 production, while the DTH response, relative monocyte numbers and thym ic weights were unchanged. With early exposure, the primary alteration was decreased nitric oxide production in Pb-treated males, whereas in Pb-treate d females nitrite production was unaltered. These results suggest that at t he Pb dosage employed, the embryo may be more sensitive to the full range o f Pb-induced immunotoxic effects with late gestational Pb exposure, and the effects of Pb on DTH function are more pronounced in females. The data als o indicate that adherent splenocytes (probably macrophages) and T lymphocyt es are the primary immune cells affected during fetal Pb exposure, and that gender may influence the impact of Pb exposure on these cells. Therefore, additional developmental immunotoxicity studies are needed to examine criti cal windows of immune development for immunotoxicity and differential susce ptibility based on gender.