Exposure to lead during critical windows of embryonic development: Differential immunotoxic outcome based on stage of exposure and gender
Exposure to lead during critical windows of embryonic development: Differential immunotoxic outcome based on stage of exposure and gender
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DOI：
10.1093/toxsci/64.1.57
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发表时间：
2001-11-01
影响因子：
3.8
通讯作者：
Dietert, RR
中科院分区：
文献类型：
--
作者：
Bunn, TL;Parsons, PJ;Dietert, RR
以前的大鼠铅(铅)研究表明，在整个妊娠期暴露会导致持续的免疫毒性，在幼年和成年后代中都能检测到。呃，差异也很明显。然而，在胚胎发育的特定阶段使用铅时，人们对铅的持续免疫毒性作用知之甚少。成年SD雌性大鼠在妊娠早期(第3~9天)或妊娠晚期(第15~21天)饮水中加入醋酸铅(或对照醋酸铅)。在妊娠晚期铅暴露的成年雌性子代中，观察到显著抑制迟发型超敏反应(DTH)反应，以及增加IL-10的产生、相对单核细胞数量和相对胸腺重量。相比之下，孕晚期染铅的雄性仔鼠IL-12的产生显著增加，IL-10的产生显著降低，而迟发型超敏反应、相对单核细胞数和胸腺重量无明显变化。在早期接触铅的男性中，主要的变化是一氧化氮的产生减少，而在铅处理的女性中，亚硝酸盐的产生没有改变。这些结果表明，在铅的剂量范围内，胚胎对妊娠晚期铅暴露引起的全方位免疫毒性作用更敏感，并且铅对雌性小鼠DTH功能的影响更为明显。这些数据还表明，胎儿铅暴露时，粘附的脾细胞(可能是巨噬细胞)和T淋巴细胞是受影响的主要免疫细胞，性别可能影响铅暴露对这些细胞的影响。因此，需要进行更多的发育免疫毒性研究，以检查免疫发育的关键窗口，以了解免疫毒性和基于性别的不同易感性。
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. However, little is known about the persistent immunotoxic effects of Pb when administered during specific stages of embryonic development. Adult Sprague-Dawley female rats were administered Pb acetate (or control acetate) in their drinking water early in gestation (days 3-9) or late in gestation (days 15-21). Significantly depressed delayed type hypersensitivity (DTH) responses as well as elevated IL-10 production, relative monocyte numbers, and increased relative thymic weights were observed in late-gestation Pb-exposed female offspring assessed as adults. In contrast, late-gestation Pb-treated male offspring had significantly increased IL-12 production and decreased IL-10 production, while the DTH response, relative monocyte numbers and thymic weights were unchanged. With early exposure, the primary alteration was decreased nitric oxide production in Pb-treated males, whereas in Pb-treated females nitrite production was unaltered. These results suggest that at the Pb dosage employed, the embryo may be more sensitive to the full range of Pb-induced immunotoxic effects with late gestational Pb exposure, and the effects of Pb on DTH function are more pronounced in females. The data also indicate that adherent splenocytes (probably macrophages) and T lymphocytes 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 critical windows of immune development for immunotoxicity and differential susceptibility based on gender.