THIS PROJECT WILL STUDY THE POTENTIALLY ENDURING EFFECT OF PRENATAL STRESS IN ORDER TO DEVELOP SUSTAINABLE SOLUTIONS TO IMPROVE THE HEALTH AND WELL-BEING AND PRODUCTIVITY OF NEONATAL, GROWING CATTLE. THE NATURE OF ONE'S LIFE IS SHAPED BY THE INTERACTION OF GENETIC AND ENVIRONMENTAL FACTORS. STRESSFUL STIMULI EXACERBATE HEALTH ISSUES AND REDUCE PRODUCTIVITY OF LIVESTOCK BY ALTERING EXPRESSION OF STRESS AND IMMUNE RESPONSE GENES. STRESS SHORTENS THE LENGTH OF HUMAN TELOMERES, THE PROTECTIVE ENDS OF CHROMOSOMES THAT MAINTAIN GENETIC INTEGRITY DURING DNA REPLICATION. GENETIC AND EPIGENETIC MECHANISMS MEDIATE NEUROENDOCRINE RESPONSES TO ENVIRONMENTAL, MANAGERIAL, AND PATHOGENIC STRESSORS. PRENATAL TRANSPORTATION STRESS OF BULL CALVES DIFFERENTIALLY METHYLATES DNA (I.E., A CHEMICAL MODIFICATION THAT ALTERS EXPRESSION) OF GENES RELATED TO BEHAVIOR, STRESS RESPONSE, AND IMMUNITY. THESE MODIFICATIONS ARE SET EARLY IN LIFE AND MAY BE ALTERED BY STRESS AND THUS INFLUENCE GENE EXPRESSION LATER IN LIFE. WE PROPOSE TO USE THE BOVINE PRENATAL STRESS MODEL TO TEST THE CONCEPT THAT STRESS PROMOTES ATTRITION OF TELOMERES (THE PROTECTORS OF CHROMOSOMAL DNA). OUR OVERARCHING HYPOTHESIS IS THAT PRENATAL STRESS ACCENTUATES THE NEGATIVE EFFECTS OF GLUCOCORTICOIDS AND CYTOKINES ON TELOMERES AND TISSUE SPECIFIC EXPRESSION OF NEUROENDOCRINE FACTORS REGULATING TEMPERAMENT AND STRESS RESPONSIVENESS. PRENATALLY STRESSED CALVES PRODUCED BY STRESSING THEIR MOTHERS MULTIPLE TIMES DURING GESTATION WILL BE USED IN OUR BOVINE MODEL FOR PRENATAL STRESS. THIS PROJECT WILL INVESTIGATE THE IMPACT OF PRENATAL STRESS ON TARGETED NEUROENDOCRINE SIGNALING SYSTEMS AND TELOMERE LENGTH. PRENATALLY STRESSED AND CONTROL CALVES WILL BE COMPARED IN MALE AND FEMALE CALVES AT 28 DAYS OF AGE WITH REGARD TO PRODUCTION OF STRESS-RELATED HORMONES AND THE LENGTH OF TELOMERES IN WHITE BLOOD CELLS. THIS RESEARCH WILL IDENTIFY NEW PATHWAYS TO TARGET WITH THERAPEUTICS OR NOVEL MANAGEMENT STRATEGIES. THERE IS A CLEAR NEED FOR DEVELOPMENT OF SENSITIVE AND ACCURATE QUANTITATIVE EARLY BIOMARKERS (I.E., HORMONES, METHYLATION PATTERNS OR TELOMERE LENGTH) OF GENETIC SUSCEPTIBILITY OR RESILIENCE TO STRESS. THE PROPOSED PROJECT WILL CONTRIBUTE TO DEVELOPMENT OF SUSTAINABLE SOLUTIONS TO IMPROVE THE HEALTH, WELL-BEING AND OVERALL PRODUCTIVITY OF NEONATAL AND GROWING ANIMALS.