PLACENTAL TOXICOLOGY

胎盘可能是特定毒性作用的一个部位。 胚胎的生长和存活，例如，镉可以 造成大鼠胎盘坏死和胎儿死亡。在.期间 在过去的三年里，进行了一些研究，以确定 人类胎盘可能会受到环境的选择性影响 在动物或人类身上检测到的水平的药物。一种体外对偶体 灌流的、循环的人胎盘制剂 研究正常的生理和毒性反应 没有母亲或婴儿参与的镉。人类 胎盘灌流系统可维持胎盘 形态(超微结构)、生理和 生化时间超过12小时。当CD是 以这样的(Cd)进入大鼠的母体灌流液 血浆为胎盘毒性剂量，有快速蓄积 胎盘中的镉，几乎没有通向胎儿回路的通道。在 在服用镉12小时后，有一剂 相关的(10、20或100nmoles/ml初始剂量)坏死增加， 亚合体滋养细胞囊泡形成、间质水肿、胎儿体积 人绒毛膜丢失(渗漏)、(12小时内)和减少 促性腺激素的合成和释放(4小时内)。这个 这项提议的目标有四个：1.建立一个 人胎盘24-36小时体外灌流模型 用于确定有毒物质的相互作用和分布 在动物体内发现的循环血液水平的环境因子 和人类，并将这个体外模型与其他 动物和人体研究。拟议的研究将涉及 了解人的正常生理功能 胎盘(激素分泌、运输过程，尤其是 受体介导的维生素磁性诱导内吞作用12 和其他营养物质以及能量代谢)；2.确定 急性接触镉产生的机制 胎盘对人和啮齿动物的毒性及其保护作用 可由其他金属(锌、硒)和其他金属提供 条件(金属硫蛋白的诱导)；3.比较急性 并找出Cd对胎盘的无作用剂量。 正常母亲和吸烟母亲的关系 金属硫蛋白含量和诱导，毒性反应，以及 急性镉对慢性低镉暴露的潜在保护作用 暴露和4.利用这种体外人胎盘灌流 调查其他疑似胎盘的可能性的模型 动物体内的毒素，如铅和氯仿，直接与胎盘有关 在控制良好的条件下，对人体有毒性。

The placenta can be a site for specific toxic action compromising the growth and survival of the conceptus, e.g., cadmium can produce placental necrosis and fetal death in rats. During the past three years, studies were undertaken to determine if the human placenta can be selectively affected by environmental agents at levels detected in animals or humans. An in vitro dual perfused, recirculating human placental preparation was developed to study the normal physiology and toxic response to cadmium without mother or baby being involved. The human placental perfusion system can maintain the placenta morphologically (ultrastructurally), physiologically and biochemically for periods in excess of 12 hours. When Cd is introduced into the maternal perfusate at such (Cd) noted in rat plasma for a placental toxic dose, there is a rapid accumulation of cd in the placental with little passage to the fetal circuit. Within twelve hours following the administration of Cd, there is a dose related (10, 20, or 100nmoles/ml initial dose) increase in necrosis, subsynctiotrophoblastic vesiculation, stromal edema, fetal volume loss (leakiness), (within 12 hours) and decrease in human chorionic gonadotropin synthesis and release (within 4 hours). The objectives of this proposal are four-fold: 1. to establish an in vitro human placental perfusion model for periods of 24-36 hours for determining the toxic interactions and distribution of environmental agents at circulating blood levels noted in animals and humans, and for comparing this in vitro model with other animal and human studies. The proposed studies would involve understanding the normal physiological functioning of the placenta (hormone secretion, transport processes, especially receptor-mediated endocytosis for vitamin magnetic induction12 and other nutrients, and energy metabolism); 2. to determine the mechanisms by which acute exposure to cadmium produces placental toxicity in the human and rodent and whether protection can be provided by other metals (Zn, Se) and under other conditions (induction of metallothionein); 3. to compare the acute effects of Cd and to find a no effect dose in placentae from normal mothers and from smoking mothers in relationship to metallothionein content and induction, toxic response, and potential protection of chronic low Cd exposure to acute Cd exposure and 4. to utilize this in vitro human placental perfusion model to investigate the potential for other suspected placental toxins in animals, e.g., Pb and chloroform, to be directly placental toxic in the human under well-controlled conditions.