White T E, Baggs R B, Miller R K
Environmental Health Sciences Center, University of Rochester Medical Center, New York 14642.
Teratology. 1990 Jul;42(1):7-13. doi: 10.1002/tera.1420420103.
During embryogenesis, maternal administration of cadmium (Cd) produces teratogenic effects, including hydrocephalus (HC), whereas later in gestation (during the fetal period), such effects have not been reported. Since there is little placental transfer of Cd late in gestation, such differences in response could be due to a lower Cd concentration in the fetus compared with the embryo after maternal Cd exposure, or could be due to a decreased sensitivity of the fetal central nervous system (CNS) to Cd. To test the susceptibility of the late gestational CNS to Cd, day 19 (sperm plug = day 0) rat fetuses were directly injected i.p. with CdCl2 (165, 100, 50 nmoles/fetus in 5 microliters saline). All fetuses in one horn were treated with Cd, while fetuses in the other horn were treated with saline. Fetuses were collected on day 21, grossly examined, weighed, fixed in Bouin's fixative, and later razor sectioned. Cd did not affect fetal viability or body weight. However, Cd caused a dose-dependent increase in hydrocephalus, with the total number of fetuses showing moderate to severe HC being 0/45, 0/11, 6/10, and 18/20 for controls, low, medium, and high doses, respectively. Mild HC was noted in one control and two low Cd fetuses. Brain necrosis was correlated with hydrocephalus, being observed in 0/45, 0/11, 5/10, and 16/20 fetuses, respectively. In medium-dose fetuses without HC or brain necrosis, extravasation of erythrocytes was noted histologically within the cortical parenchyma, suggesting that hemorrhaging may lead to brain necrosis and hydrocephalus in Cd-exposed fetuses. Thus, the fetal CNS is susceptible to the toxic effects of Cd.
在胚胎发生过程中，母体给予镉（Cd）会产生致畸作用，包括脑积水（HC），而在妊娠后期（胎儿期），尚未有此类作用的报道。由于妊娠后期Cd很少通过胎盘转运，这种反应差异可能是由于母体接触Cd后胎儿体内的Cd浓度低于胚胎，或者可能是由于胎儿中枢神经系统（CNS）对Cd的敏感性降低。为了测试妊娠后期CNS对Cd的易感性，在第19天（阴道栓形成日=第0天）的大鼠胎儿经腹腔直接注射CdCl2（165、100、50纳摩尔/胎儿，溶于5微升盐水中）。一侧子宫角的所有胎儿用Cd处理，而另一侧子宫角的胎儿用盐水处理。在第21天收集胎儿，进行大体检查、称重，用Bouin固定液固定，随后用剃须刀切片。Cd不影响胎儿的存活率或体重。然而，Cd导致脑积水呈剂量依赖性增加，对照组、低剂量组、中剂量组和高剂量组出现中度至重度HC的胎儿总数分别为0/45、0/11、6/10和18/20。在1只对照胎儿和2只低剂量Cd处理的胎儿中发现轻度HC。脑坏死与脑积水相关，分别在0/45、0/11、5/10和16/20的胎儿中观察到。在没有脑积水或脑坏死的中剂量胎儿中，组织学上在皮质实质内观察到红细胞外渗，这表明出血可能导致接触Cd的胎儿发生脑坏死和脑积水。因此，胎儿CNS对Cd的毒性作用敏感。
