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

试点研究——多氯联苯在生殖中的毒性和雌激素作用

• 批准号: 6353703
• 负责人: GEORGE L MCCOY
• 金额: $ 23.37万
• 依托单位: BENEDICT COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353703
• 关键词: Peromyscus; behavioral /social science research tag; cytotoxicity; electrophoresis; endocrine disorder; environmental toxicology; estrogen inhibitor; female reproductive system disorder; fertility; flow cytometry; halobiphenyl /halotriphenyl compound; immunocytochemistry; laboratory rat; male reproductive system disorder; plaque assay; radioimmunoassay; secretion; sex behavior; sperm analysis; tissue /cell culture

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.

我们的目标是阐明环境保护机制 多氯联苯(PCbs)损害生殖功能。重点是 关于多氯联苯对小鼠激素分泌细胞的影响 生殖系统。据推测，多氯联苯会影响生殖 以两种不同的方式起作用--作为抗雌激素或雌激素 和/或通过直接对小鼠的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抗雌激素或 雌激素活性。然后将使用细胞培养进行研究1) 为了测试这些多氯联苯对促性腺激素细胞活性的直接影响， 哺乳细胞、间质细胞和颗粒细胞；2)评估Pre-Pre 体内暴露于多氯联苯使细胞对多氯联苯的毒性作用敏感 体外；3)确定多氯联苯诱导的细胞死亡是否涉及细胞凋亡 用吖啶橙和碘化丙啶染色技术 细胞核，DNA电泳，3‘-羟基DNA末端的凋零标记，以及Flow 细胞术；以及4)确定多氯联苯是否直接作用于内分泌细胞 为了改变基础和激素刺激的黄体生成素，卵泡- 刺激素、催乳素和睾酮的释放 放射免疫分析和斑块分析。在其他实验中，多氯联苯将 给成年雄性大鼠灌胃，观察其对睾丸的影响， 附睾腺和男性附腺重量和组织学；睾丸 精子产生和附睾精子储存；精子形态；以及 荷尔蒙分泌。然后将多氯联苯注射到雌性大鼠身上，以 测定对发情周期、排卵和分泌的影响 生殖荷尔蒙。终止治疗的可能性 多氯联苯逆转多氯联苯的影响也将得到调查。最后， 多代接触多氯联苯对生殖过程的影响 将会被研究。这些调查的结果不仅应该提供 对我们理解印刷电路板的方式的重要见解 环境污染物会干扰生殖过程，但 也应该开始定义这些效应产生的机制 调解过的。