PILOT STUDY--TOXIC AND ESTROGENIC ACTIONS OF PCB IN REPRODUCTION

我们的目标是阐明环境影响的机制 多氯联苯（PCBs）损害生殖功能。 重点 放置在多氯联苯的影响，分泌细胞的 生殖系统 据推测，多氯联苯可以影响生殖 以两种不同的方式起作用--作为抗雌激素或雌激素 和/或直接对内分泌细胞产生毒性作用， 生殖系统 在我们的研究中，多氯联苯将首先在 体外和体内，以确定它们是否具有任何抗雌激素或 雌激素活性 然后使用细胞培养物进行研究1） 为了测试这些多氯联苯对促性腺激素细胞活力的直接影响， 催乳细胞、间质细胞和颗粒细胞; 2）评估是否存在预- 体内暴露于多氯联苯会使细胞对多氯联苯的毒性作用敏感， 体外; 3）确定PCB诱导的细胞死亡是否涉及凋亡 采用吖啶橙子和碘化丙啶染色技术， 细胞核，DNA电泳，3 '-OH DNA末端的Apoptag标记，和流动 流式细胞术;以及4）确定多氯联苯是否直接作用于内分泌细胞 改变基础和卵泡刺激的黄体生成素，卵泡- 刺激激素、催乳素和睾酮的释放， 放射免疫测定和噬斑测定。 在其他实验中，PCB将 对成年雄性大鼠给药以研究对睾丸的影响， 附睾和雄性副腺重量和组织学;睾丸 精子产生和附睾精子储存;精子形态;以及 激素分泌 然后将多氯联苯给予雌性大鼠， 确定对发情周期、排卵和 生殖激素 终止治疗的可能性 多氯联苯逆转多氯联苯的影响也将被调查。 最后 多代接触多氯联苯对生殖过程的影响 将被研究。 这些调查结果不仅提供了 重要的洞察力，我们的方式，PCB的理解 环境污染物会干扰生殖过程， 也应该开始定义这些影响的机制， 调解。

Our objective is to elucidate mechanisms by which environmental polychlorinated biphenyls (PCBs) impair reproductive function. Emphasis is placed on the effects of PCBs on hormone-secreting cells of the reproductive system. It is hypothesized that PCBs can affect reproductive function in two different ways - by acting as anti-estrogens or estrogens and/or by exerting toxic effects directly on endocrine cells of the reproductive system. In our studies, PCBs will first be tested both in vitro and in vivo to determine whether they possess any anti-estrogenic or estrogenic activity. Studies will then be conducted using cell cultures 1) to test the direct effect of these PCBs on the viability of gonadotrophs, lactotrophs, Leydig cells, and granulosa cells; 2) to assess whether pre- exposure to PCBs in vivo sensitizes cells to the toxic effects of PCBs in vitro; 3) to determine whether PCB-induced cell death involves apoptosis using the techniques of acridine orange and propidium iodide staining of nuclei, DNA electrophoresis, Apoptag labeling of 3'-OH DNA ends, and flow cytometry; and 4) to determine whether PCBs act directly on endocrine cells to alter basal and hormone-stimulated luteinizing hormone, follicle- stimulating hormone, prolactin,a nd testosterone release using radioimmunoassay and plaque assays. In additional experiments, PCBs will be administered to adult male rats to investigate effects on testicular, epididymal, and male accessory gland weights and histology; testicular sperm production and epididymal sperm storage; sperm morphology; and hormone secretion. PCBs will then be administered to female rats to determine effects on estrous cyclicity, ovulation, and secretion of reproductive hormones. The possibility that termination of treatment with PCBs reverses the effects of PCBs also will be investigated. Finally, the effects of multigenerational exposure to PCBs on reproductive processes will be studied. Results from these investigations should not only provide important insight into our understanding of the manner in which PCB environmental pollutants act to interfere with reproductive processes but should also begin to define the mechanisms by which these effects are mediated.