Impact of Egg Quality on Gene Expression and Behavior

卵子质量对基因表达和行为的影响

• 批准号: 6787309
• 负责人: RICHARD M SCHULTZ
• 金额: $ 37.88万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6787309
• 关键词: behavior test; behavioral genetics; cooperative study; developmental genetics; egg /ovum; embryo /fetus tissue /cell culture; embryology; gene expression; genetic library; genetic screening; genetically modified animals; learning; memory; microarray technology; nucleic acid sequence; stress; subtraction hybridization; technology /technique development

DESCRIPTION (provided by applicant): It is now clearly recognized from egg donation studies that it is the egg and not the reproductive tract that is the cause of reduced fertility or infertility. Remarkably, the molecular underpinnings of what constitutes an egg of "high" quality are essentially unknown. Specific Aim 1 will test the hypothesis that a specific pattern of gene expression characterizes eggs of high quality by using suppression subtractive hybridization to identify genes that are differentially expressed in meiotically and developmentally competent high quality mouse eggs. These genes will be used to construct an "oocyte chip" that will be used to ascertain if a specific set of these genes is mis-expressed, or inappropriately expressed, in oocytes whose developmental competence is compromised, e.g., oocytes that develop during in vitro culture; oocytes derived from small antral follicles, oocytes obtained from hyperstimulated mice, and oocytes obtained from aged mice. The Fetal Origins of Adult Disease hypothesis posits that specific diseases in the adult are the result of the fetus's adaptations in utero to maternal under nutrition or malnutrition. This hypothesis may extend to the preimplantation stage, since reducing protein intake during this time in the rat results in such long-term changes, and the culturing of preimplantation embryos leads to offspring that exhibit altered behavior. Specific Aim 2 will test the hypothesis that low quality eggs give rise to offspring that exhibit perturbations in behavior by analyzing these offspring with a battery of behavioral assays. Treatment of human infertility with Assisted Reproductive Technology (ART) entails embryo culture that can result in changes in gene expression. Even eggs of high quality (and the resulting preimplantation embryos) that are used in ART may be at risk simply due to embryo culture conditions. Specific Aim 3 will test the hypothesis that modifications of culture conditions can alleviate the effect of embryo culture on the culture-associated perturbations observed in gene expression and behavior in the offspring. Results of these experiments will establish the molecular basis of egg quality and will provide critical information regarding the effect on behavior in offspring derived from low quality eggs, as well as the effect of ART procedures on gene expression and behavior.

描述（由申请人提供）：现在可以从鸡蛋捐赠研究中可以清楚地认识到是卵是卵子降低或不育的原因而不是生殖道。值得注意的是，构成“高”质量卵的分子基本上是未知的。特定的目标1将检验以下假设：基因表达的特定模式通过使用抑制减去杂交来表征高质量的卵，以鉴定在减数分裂和发育效率上有能力的高质量小鼠卵中差异表达的基因。这些基因将用于构建“卵母细胞芯片”，该基因将用于确定这些特定基因是否表达了或不当表达的卵母细胞，其发育能力受到损害，例如，在体外培养过程中会造成发展的卵母细胞；源自小卵泡的卵母细胞，从过度捕获的小鼠获得的卵母细胞以及从老年小鼠获得的卵母细胞。成人疾病假设的胎儿起源表明，成年人的特定疾病是胎儿在营养或营养不良下对孕产妇的适应性的结果。该假设可能会扩展到植入前阶段，因为在这段时间内减少蛋白质摄入会导致这种长期变化，并且植入前胚胎的培养会导致表现出改变行为的后代。特定的目标2将检验以下假设：低质量的卵会通过用一系列行为测定法分析这些后代，从而产生后代。用辅助生殖技术（ART）处理人类不育症需要胚胎培养，这可能导致基因表达变化。即使是在艺术中使用的高质量卵（以及所得的植入前胚胎），也可能仅由于胚胎培养条件而面临风险。具体目标3将检验以下假设：培养条件的修改可以减轻胚胎培养对后代基因表达和行为中与培养相关的扰动的影响。这些实验的结果将建立卵质量的分子基础，并将提供有关对低质量鸡蛋的后代行为影响的关键信息，以及艺术程序对基因表达和行为的影响。