Grant: Discovery Grants Program - Individual

The Maternal Environment: Influence on Early Mammalian DevelopmentCultured 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.