TOXIC EFFECTS ON EARLY EMBRYONINC DEVELOPMENT

对早期胚胎发育的毒性作用

• 批准号: 3755135
• 负责人: W RICHARD DUKELOW
• 金额: --
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3755135
• 关键词: body physical characteristic; calcium flux; carbon tetrachloride; cell cell interaction; chemical kinetics; congenital disorders; cytotoxicity; early embryonic stage; embryo /fetus culture; embryo /fetus toxicology; embryogenesis; environmental contamination; environmental toxicology; halobiphenyl /halotriphenyl compound; in vitro fertilization; laboratory mouse; organic chemicals; protein biosynthesis; tissue /cell culture; toluene; trichloroethylene; vapor

The proposed studies will examine the effect of selected groundwater contaminants (the volatile organic chemicals initially studied in the previous three years of this grant) and polychlorinated biphenyls on specific mechanisms of action relating to the reproductive process. This will include direct effects on the sperm, egg, and embryo as they proceed through the preimplantation stages of pregnancy, during implantation and embryonic development and effects exerted at the time of labor and parturition. These studies will build on our existing research program and will utilize in vitro methods of cell and tissue culture including techniques for in vitro fertilization. Since some of the in vitro methods proposed are applied for the first time in toxicity studies, additional in vivo assay methods will be carried out to verify the in vitro approach and findings. Several of the proposed test chemicals have been implicated in reproductive dysfunction in occupationally exposed workers, yet little is known about the etiology. Specifically, these studies will: 1) complete in vivo and in vitro evaluation of the VOCs previously studied and expanded this work to the PCBs; 2) develop in vitro assay methods using microsurgically divided embryos to characterize effects on individual embryonic cells; 3) use the above methods to determine specific mechanistic action of the VOCs and PCBs on reproduction and mechanisms of cell-cell communication; 4) determine the fertility of offspring exposed to PCBs in utero and through puberty; 5) in vitro testing, not only of the chemicals in question but also biodegradation products; 6) determine the effects of test chemicals on sperm intracellular calcium concentrations and hydrogen peroxide production; 7) application of computer-aided image analysis for effects on sperm motion analysis; 8) chemical effects on sperm capacitation; 9) effects on myometrial gap junctional communication in vitro; 10) effect of in vitro exposure of uterine strips to the test chemicals on contractility; and 11) mechanisms of myometrial gap junctional communication effects as it relates to labor induction.

拟议的研究将检查选定地下水的影响 污染物（最初研究的挥发性有机化学物质 此项拨款的前三年）和多氯联苯 与生殖过程有关的具体作用机制。 这 将包括对精子、卵子和胚胎进行过程中的直接影响 通过妊娠的着床前阶段、着床期间和 胚胎发育和在分娩时产生的影响 分娩。 这些研究将建立在我们现有的研究计划的基础上 将利用细胞和组织培养的体外方法，包括 体外受精技术。 由于一些体外方法 提议首次应用于毒性研究，另外 将进行体内测定方法来验证体外方法和 发现。 一些拟议的测试化学品已涉及 职业暴露工人的生殖功能障碍，但很少有 了解病因。 具体来说，这些研究将：1）完成 对先前研究和扩展的 VOC 进行体内和体外评估 PCB 的这项工作； 2) 开发体外测定方法 显微外科分割胚胎以表征对个体的影响 胚胎细胞； 3）用上述方法确定具体机理 VOCs和PCBs对细胞繁殖和机制的作用 沟通; 4) 确定暴露于多氯联苯的后代的生育力 子宫内和青春期； 5) 体外测试，不仅仅是化学品 有问题的还有生物降解产品； 6) 确定效果 测试化学物质对精子细胞内钙浓度和氢的影响 过氧化物生产； 7）计算机辅助图像分析的应用 对精子运动分析的影响； 8）对精子的化学作用 获能； 9) 对子宫肌层间隙连接通讯的影响 体外； 10) 试管条体外暴露对试验的影响 化学物质对收缩性的影响； 11) 子宫肌层间隙连接机制 与引产相关的沟通效果。