Effects of prenatal exposure to inorganic arsenic on the mice offspring

世界各国都报告了天然无机砷对地下水的污染，使5000多万人受到严重威胁。虽然长期砷暴露对健康的影响已经得到了广泛的研究，但其对发育中的生物体的潜在影响迄今为止几乎没有被研究过。由于发育中的生物体往往比成人对环境威胁更敏感，因此本研究着重探讨了产前无机砷暴露对胎儿和后代的可能影响。i）母体砷暴露对胎儿硒和硒酶的影响。C57 BL/6 J小鼠在GD 7 -16之间暴露于不会产生明显毒性的剂量的亚砷酸盐。在GD 17，解剖小鼠，并测定组织中硒、砷和硒酶的水平。还评估了饮食诱导的硒缺乏的影响。结果发现，硒缺乏促进砷在母鼠和胎儿组织中的积累，与对照组（硒充足）相比，可达1.5倍。砷暴露还影响了组织硒水平和硒酶活性。在所观察到的影响，活性的硫氧还蛋白还原酶（TRXR）在胎儿肝脏中的增强和抑制硒充足和缺乏的状态，分别;这种修改硒状态未观察到在母体组织。提示硒缺乏时砷的毒性可能增强，胎儿对硒状态的变化比成人更敏感。（i）观察了妊娠期砷暴露母鼠所生子代的行为。在非明显毒性剂量下，砷暴露可使某些运动功能发育迟缓，并使8周龄的旷场行为发生改变，表明产前砷暴露可导致行为改变，并伴有脑单胺类神经递质的变化。

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.