PBC EFFECTS ON UTERINE WALL

PBC 对子宫壁的影响

• 批准号: 6296558
• 负责人: CRAIG HARRIS
• 金额: $ 15.1万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296558
• 关键词: birth; calcium flux; environmental toxicology; fluorescent dye /probe; gap junctions; glutathione; halobiphenyl /halotriphenyl compound; hormone receptor; laboratory rat; membrane channels; muscle contraction; myometrium; northern blottings; phosphorylation; premature labor; protein kinase C; reproductive development; steroid hormone biosynthesis; steroid hormone receptor; tissue /cell culture; western blottings

Reproduction and development are highly integrated, hormonally dependent processes that can be acutely sensitive to chemical insult. Several halogenated polycyclic aromatic hydrocarbons, which are common Superfund contaminants, exhibit agonist as well as antagonist hormonal activity and are therefore potential reproductive and developmental toxicants. This project is composed of three subprojects. Each subproject has a different approach to the study of reproductive toxicity, yet the subprojects share the overall objectives of (1) characterizing the effects of selected halogenated polycyclic aromatic hydrocarbons on reproduction and development, (2) investigating the mechanisms that initiate and mediate the chemical-induced alterations in reproduction and development, (3) assessing possible health risks arising from exposure to these chemicals. This subproject will focus on the process of parturition, investigating the potential role of PCBs in prematurity, post-maturity and dystocia (difficult labor). The proposed research will test the hypothesis that PCBs modulate uterine contraction in a direct and congener-specific manner, and that these PCBs thereby also have the potential to alter parturition. PCBs will first be assessed for effects on contraction of isolated uterine strips followed by in vivo experiments to determine if the PCB modifies parturition. Additionally, the mechanism(s) of action of the PCBs will be examined. It is hypothesized that direct actions of PCBs on uterine contraction are due to mechanisms involving steroidogenic action, gap junctional communication, calcium homeostasis, and/or glutathione status, possibly in an interactive manner.

繁殖和发展高度整合，荷尔蒙依赖性 可以对化学损伤敏感的过程。 一些 卤代多环芳烃，这是常见的超级基金 污染物，展示激动剂以及拮抗剂激素活性和 因此，是潜在的生殖和发育毒性。 这 项目由三个子标记组成。 每个子项目都有一个 研究生殖毒性的不同方法，但是 子标题共享（1）表征的总体目标 选定的卤化多环芳族烃对 繁殖和发展，（2）调查的机制 引发并介导化学诱导的繁殖改变和 开发，（3）评估暴露于暴露的可能健康风险 这些化学物质。 该子标记将重点放在 分娩，调查PCB在早产中的潜在作用， 成熟后和肌不满（艰难的劳动）。 拟议的研究将 测试PCB在直接调节子宫收缩的假设 和特定于同类的方式，因此这些PCB也具有 改变分娩的潜力。 PCB将首先评估效果 孤立的子宫条的收缩，然后进行体内实验 确定PCB是否修改了分娩。 另外， 将检查PCB的作用机制。 它是假设的 PCB对子宫收缩的直接作用是由于机制 涉及类固醇作用，间隙连接通信，钙 稳态和/或谷胱甘肽状态，可能在互动中 方式。