Wier P J, Miller R K, Maulik D, DiSant'Agnese P A
Departments of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, New York 14642.
Toxicol Appl Pharmacol. 1990 Aug;105(1):156-71. doi: 10.1016/0041-008x(90)90367-4.
Cadmium, a placental toxicant in rodents, was studied in the in vitro isolated dually perfused human placental lobule for periods of up to 12 hr to determine if cadmium can also be toxic in the human placenta. Placental lobules were perfused with a modified M199 medium containing 0, 10, 20, or 100 nmol of cadmium chloride/ml added only initially to the maternal perfusate. Every 4 hr, the perfusates in both the maternal and the fetal circuits were replaced with fresh perfusate containing no Cd. Measurements during perfusion were oxygen consumption, net fetal oxygen transfer, fetal pressure, fetal volume loss, glucose utilization, lactate production, human chorionic gonadotropin (hCG), and zinc transfer. Postperfusion, morphology, and tissue slice studies were performed to evaluate cellular metabolic function and uptake of an amino acid (alpha-[14C]-aminoisobutyric acid). In all cadmium experiments, there were no significant alterations in oxygen consumption, lactate production, glucose utilization, or amino acid uptake compared with controls; however, there were dose-related changes in the synthesis and release of the protein hormone, hCG, beginning within 4 hr of initial exposure to Cd. There were also dose-related volume loss from the fetal vasculature (greater than 6 ml/hr) and ultrastructural changes (subsyncytiotrophoblastic vesiculations, stromal edema, vacuoles in Hofbauer cells), with necrosis at 100 nmol Cd/ml occurring between 5 and 8 hr. Cadmium (10 nmol/ml) reduced the placental transfer of zinc into the fetal circuit. Thus, the human placenta is a site for toxic action of cadmium and is at least as sensitive as the rodent placenta to the actions of cadmium. In addition, these human studies demonstrated a selectivity in the toxic effects with a maintenance of carbohydrate metabolism and amino acid uptake even after 12 hr of exposure with placental Cd burdens of 151 +/- 37 nmol/g, but with the earliest (within 4 hr) dose-related functional alterations occurring in protein hormone production and zinc transfer followed by later changes in morphology with a tissue Cd burden of 46.5 +/- 4.0 nmol/g.
镉是啮齿动物体内的一种胎盘毒物，本研究在体外分离的双灌注人胎盘小叶中进行了长达12小时的实验，以确定镉在人胎盘中是否也具有毒性。向胎盘小叶灌注改良的M199培养基，该培养基仅在最初添加到母体灌注液中，含有0、10、20或100纳摩尔/毫升的氯化镉。每4小时，用不含镉的新鲜灌注液替换母体和胎儿循环中的灌注液。灌注期间的测量指标包括耗氧量、胎儿净氧转运、胎儿压力、胎儿容积损失、葡萄糖利用、乳酸生成、人绒毛膜促性腺激素（hCG）和锌转运。灌注后，进行形态学和组织切片研究，以评估细胞代谢功能和氨基酸（α-[14C]-氨基异丁酸）的摄取情况。在所有镉实验中，与对照组相比，耗氧量、乳酸生成、葡萄糖利用或氨基酸摄取均无显著变化；然而，从最初接触镉开始4小时内，蛋白质激素hCG的合成和释放就出现了剂量相关变化。胎儿血管系统也出现了剂量相关的容积损失（大于6毫升/小时）和超微结构变化（合体滋养层下空泡形成、基质水肿、霍夫鲍尔细胞内出现空泡），在100纳摩尔/毫升镉时，5至8小时出现坏死。镉（10纳摩尔/毫升）减少了锌向胎儿循环的胎盘转运。因此，人胎盘是镉毒性作用的部位，至少与啮齿动物胎盘对镉作用的敏感性相同。此外，这些人体研究表明，即使在暴露12小时、胎盘镉负荷为151±37纳摩尔/克的情况下，碳水化合物代谢和氨基酸摄取仍能维持，但最早在接触后4小时，蛋白质激素产生和锌转运就出现了剂量相关的功能改变，随后在组织镉负荷为46.5±4.0纳摩尔/克时形态学出现了后期变化。
