Effects of prenatal exposure to inorganic arsenic on the mice offspring

世界上许多国家都报道了地下水受到天然无机砷污染的情况，这对5000多万人构成了严重威胁。虽然长期接触砷对健康的影响已进行了广泛的研究，但迄今为止几乎没有研究过它对发育中的生物体的潜在影响。由于发育中的生物往往比成人对环境威胁更敏感，本研究侧重于产前接触无机砷对胎儿和后代的可能影响。1)母体砷暴露对胎儿硒和硒酶的影响。C57BL/6J小鼠在GD7-16之间不暴露于亚砷酸盐剂量。在GD17上解剖小鼠，测定组织中硒、砷和硒酶的水平。还评估了饮食引起的硒缺乏的影响。研究发现，缺硒组砷在母体和胎儿组织中的积累量是富硒组的1.5倍。此外，砷暴露影响了硒的组织水平和硒酶的活性。在观察到的影响中，硒充足和硒缺乏状态下，胎儿肝脏中硫氧还嘌呤还原酶（TRxR）活性分别增强和抑制；在母体组织中未观察到硒状态的改变。这些结果表明，硒缺乏可能会增强砷的毒性，胎儿对硒状态的变化比成人更敏感。li)研究了妊娠期暴露于砷的坝鼠所生后代的行为。在未出现明显毒性的剂量下，砷暴露可导致8周龄幼鼠部分运动功能发育迟缓，并改变其野外行为，表明产前砷暴露可导致幼鼠行为改变，并伴有脑单胺的改变。

Contamination of groundwater with naturally-derived inorganic arsenic has been reported from various counties in the world, pausing serious threat to more than 50 millions of people. Although the health effects of chronic arsenic exposure has been extensively investigated, its potential effects on developing organisms have scarcely been examined so far. Since developing organism are often more sensitive to environmental threat than the adults, the present study focused on the possible effects of prenatal exposure to inorganic arsenic on fetus and offspring.i) Effect of maternal arsenic exposure on selenium and selenoenzymes in fetus. C57BL/6J mice were exposed to arsenite at doses that would not overt toxicity between GD7-16. On GD17, mice were dissected, and tissue levels of selenium, arsenic and selenoenzymes were determined. Effect of dietary-induced selenium deficiency was also evaluated. It was found that selenium deficiency facilitated the accumulation of arsenic both in motemal and fetal tissues up to 1.5 fold compared to control (Se sufficient) group. Also, arsenic exposure affected the tissue levels of selenium and selenoenzyme activities. Among the observed effects, activity of the thioredoxine reductase (TRxR) in the fetal liver was enhanced and suppressed in Se sufficient and deficient status, respectively ; such modification by Se status was not observed in maternal tissues. These results suggested that the toxicity of arsenic may be enhanced under Se deficiency and that fetus is more sensitive to the change of Se status than adults. li) The behavior of offspring bom to dam mice exposed to arsenic during gestation was examined. At the doses that was not overtly toxic, development of some motor functions were retarded and the open-field behavior at 8wk of age was altered by the arsenic exposure, indicating that prenatal arsenic exposure could result in altered behavior, which was accompanied by some changes in brain monoamines.