FUNCTIONAL GENOMICS OF ENHANCED EMBRYO, FETAL, AND NEONATAL DEVELOPMENT AND SURVIVAL IN SWINE
Project Number: 1265-31000-094-00
Start Date: Jul 26, 2007
End Date: Jul 25, 2012
1. Establish benchmark transcriptome profiles induced by uterine stress during gestation that are predictive of altered physiological mechanisms in key organs critical to the piglet immune and metabolic stress responses. 2. Identify critical gene(s), gene products, and their mechanism of action in the stress response of piglets associated with morbidity, growth rate, and body composition. 2.A. Identify key secretory proteins that are regulated by stress in the preweaning pig. 2.B. Identify key secretory proteins produced by adipose tissue that are regulated by stress in the preweaning pig. 3. Develop comprehensive in vitro models to analyze the mechanistic role of select, important developmental or metabolic factors in mediating the organism’s response to stresses via functional genomic approaches. 3.A. Determine the physiological mechanisms of key stress-regulatory proteins that regulate nutrient partitioning in the liver and adipose tissue. 3.B. Characterize the role of trophectoderm-derived estrogen as a modulator of “programmed” set points that determines the development potential of the peri-implantation embryo. 4. Define the repertoire of biomarkers that may be predictive of neonatal growth potential by using models of induced metabolic stress.
High preweaning mortality or impaired stress-related growth of live-born piglets continue to be major problems that negatively impact commercial swine production. Piglets exhibiting decreased vitality are at greater risk of morbidity or death and a decreased growth rate extending the farrow-to-market time, which results in increased producer costs. Considering embryo development as a continuum, it is plausible that abnormal piglet development and loss through adulthood is a consequence of aberrant embryonic/uterine development. This research will identify physiological mechanisms modulating piglet stress responses to pinpoint targets for interventions to improve “at risk” piglet survival. The research addresses three elemental issues 1) elucidation of the relationship between developmental perturbations and etiology of abnormal postnatal stress responses, 2) paucity of predictive screening tools for “at risk” neonates, and 3) lack of interventions to ameliorate postnatal development of “at risk” piglets. The impact of the uterine milieu on alterations of key physiological mechanisms that modulate stress response in metabolic or immune organs will be evaluated by comparative transcriptomic analysis between induced intrauterine growth retardation (IUGR), i.e. runting, and control concepti. To identify postnatal stress responses that are disrupted and persist ex utero as a consequence of in utero growth retardation or parturition complications and detect compensatory mechanisms, the gene expression of key metabolic and immune tissues from growth retarded piglets, (induced IUGR or spontaneous IUGR) and piglets exhibiting decreased vitality will be assessed by in-depth proteomic or transcriptomic analyses throughout the preweaning period. Functional analyses utilizing in vitro model systems and technologies, such as RNAi, will evaluate the mechanistic role of specific stress-related factors/pathways that are identified in metabolically important tissues. The relevance of putative stress-related factors/pathways will be assessed in vivo, employing distinct models of induced metabolic stress. The knowledge acquired will enable 1) the discovery of new biomarkers indicative of metabolic or immune stress response, 2) the identification physiological mechanisms/factors that can be targeted to develop new improved interventions that decrease mortality and days to market of “at risk” piglets and 3) the establishment of public “systems biology” database for specific gestational and environmental stresses.