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: 6941214
• 负责人: RICHARD M SCHULTZ
• 金额: $ 36.08万
• 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/6941214
• 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）：现在从卵子捐赠研究中清楚地认识到，导致生育能力下降或不孕的原因是卵子而不是生殖道。值得注意的是，构成“高”质量鸡蛋的分子基础基本上是未知的。具体目标 1 将通过使用抑制消减杂交来鉴定在减数分裂和发育能力良好的高质量小鼠卵中差异表达的基因，从而检验基因表达的特定模式表征高质量卵的假设。这些基因将用于构建“卵母细胞芯片”，用于确定这些基因中的一组特定基因在发育能力受到损害的卵母细胞（例如在体外发育的卵母细胞）中是否错误表达或不适当表达。文化;来自小窦卵泡的卵母细胞、从过度刺激的小鼠获得的卵母细胞以及从老年小鼠获得的卵母细胞。成人疾病的胎儿起源假说认为，成人的特定疾病是胎儿在子宫内适应母亲营养不足或营养不良的结果。这一假设可能会延伸到植入前阶段，因为在此期间减少大鼠的蛋白质摄入量会导致这种长期变化，并且植入前胚胎的培养会导致后代表现出行为改变。具体目标 2 将通过一系列行为分析对低质量卵子产生的后代进行行为扰动的假设进行检验。使用辅助生殖技术（ART）治疗人类不孕症需要胚胎培养，这可能会导致基因表达的变化。即使是用于 ART 的高质量卵子（以及由此产生的植入前胚胎）也可能仅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：改变培养条件可以减轻胚胎培养对后代基因表达和行为中观察到的培养相关扰动的影响。这些实验的结果将建立卵子质量的分子基础，并将提供关于低质量卵子对后代行为的影响以及 ART 程序对基因表达和行为的影响的关键信息。