Oxidative stress, apoptosis, and germ cell development

氧化应激、细胞凋亡和生殖细胞发育

• 批准号: 6627739
• 负责人: MARK HANNINK
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627739
• 关键词: apoptosis; beta galactosidase; biological models; biological signal transduction; disease /disorder proneness /risk; embryogenesis; environmental exposure; fertility; free radical oxygen; gene environment interaction; gene expression; genetic susceptibility; genetically modified animals; germ cells; gonads; hazardous substances; laboratory mouse; oxidation reduction reaction; oxidative stress; terminal nick end labeling; tissue /cell culture; toxicant interaction; transcription factor

DESCRIPTION (provided by applicant) Exposure to environmental toxicants adversely affects human fertility. The physiological sites of action and the molecular mechanisms whereby environmental toxicants perturb human fertility are poorly understood. Studies of the environmental and genetic mechanisms of infertility suggest that aberrant development of germ cells is a major cause of human infertility. A common property of diverse environmental toxicants is the ability to perturb cellular redox homeostasis and induce oxidative stress. The first hypothesis to be tested is that oxidative stress will adversely affect germ cell development through increased apoptosis of primordial germ cells. An important response of cells to oxidative stress is induction of the oxidative stress response, which protects cells from damage caused by reactive oxygen species (ROS) produced during oxidative stress. The second hypothesis to be tested is that the protective actions of the oxidative stress response will extend to protection against apoptosis. The investigator will develop transgenic model systems to test the relationship between oxidative stress, the protective oxidative stress response, and apoptotic mechanisms important for primordial germ cell development.

描述（由申请人提供） 暴露于环境毒物对人类生育能力有不利影响。 的 作用的生理部位和分子机制， 人们对环境毒物干扰人类生育能力知之甚少。 对不孕症的环境和遗传机制的研究表明， 生殖细胞的异常发育是人类不育的主要原因。 不同环境毒物的一个共同特性是干扰 细胞氧化还原稳态并诱导氧化应激。 第一种假设 氧化应激会对生殖细胞产生不利影响， 通过增加原始生殖细胞的凋亡来促进发育。 一个 细胞对氧化应激的一个重要反应是诱导氧化应激， 应激反应，保护细胞免受活性氧引起的损伤 氧化应激过程中产生的活性氧（ROS）。 第二个假设是 测试的是，氧化应激反应的保护作用将 延伸到对细胞凋亡的保护。 研究人员将开发 转基因模型系统来测试氧化应激， 保护性氧化应激反应和凋亡机制重要 原始生殖细胞的发育。