The maternal environment: influence on early mammalian development

母体环境：对哺乳动物早期发育的影响

• 批准号: 138317-2011
• 负责人: Watson, Andrew
• 金额: $ 3.42万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569334
• 关键词: maternal; environment; influence; early; mammalian

The Maternal Environment: Influence on Early Mammalian Development Cultured mammalian embryos from all species have a reduced pregnancy rate following embryo transfer, display aberrant patterns and levels of gene expression, and are prone to metabolic and growth disorders. It is important to increase our understanding of the normal relationships that exist between the embryo and its external environment during the first few days of development and then use this information to improve embryo culture. Principal Objective: Our recent discoveries indicating that endoplasmic reticulum (ER) stress pathways are active during early mammalian development are active provide a foundation for our studies over the next 5 years. Our studies will focus on understanding the impact of the ER stress pathways on preimplantation development and whether activation of ER stress pathways is a critical component of the adaptive mechanism early embryos employ to offset the deleterious consequence of culture on their development. Our hypothesis is that ER stress pathway activation is protective and enables cultured preimplantation embryos to proceed through the first week of development in vitro. We will investigate the role of each ER stress pathway and determine their function during the first week of development by localizing their proteins, blocking the expression of their proteins and also by activating ER stress pathways and employing antioxidants to result in improved culture environments for the production of early embryos in culture. Significance: Research is required to define all of the vital components that support early development. We will uncover new information regarding the regulation of preimplantation development. This information is required to understand the effects of environmental mediators on embryonic development and to reveal the functional roles of ER stress pathways during preimplantation development.

母体环境对哺乳动物早期发育的影响 所有物种的哺乳动物培养胚胎在胚胎移植后的妊娠率都降低，显示出异常的基因表达模式和水平，并且易于发生代谢和生长障碍。重要的是要增加我们对胚胎发育最初几天内胚胎与外部环境之间正常关系的了解，然后利用这些信息来改善胚胎培养。主要目的：我们最近的发现表明，内质网（ER）应激途径是活跃的早期哺乳动物的发展是活跃的，为我们提供了一个基础，在未来5年的研究。我们的研究将集中在了解ER应激途径对植入前发育的影响，以及ER应激途径的激活是否是早期胚胎用来抵消培养对其发育的有害后果的适应机制的关键组成部分。我们的假设是，ER应激途径的激活是保护性的，使培养的植入前胚胎进行通过第一周的发展在体外。我们将研究每个ER应激途径的作用，并通过定位其蛋白质，阻断其蛋白质的表达以及激活ER应激途径和采用抗氧化剂来确定它们在发育的第一周内的功能，从而改善培养环境以生产培养中的早期胚胎。意义：需要研究来确定支持早期发展的所有重要组成部分。我们将揭示有关胚胎植入前发育调控的新信息。这些信息是了解环境介质对胚胎发育的影响，并揭示ER应激途径在植入前发育中的功能作用所必需的。