** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** IN UTERO HEAT STRESS (IUHS) IS A THREAT TO SWINE WELFARE THAT WILL BECOME INCREASINGLY COMMON AS TEMPERATURES RISE AND EXTREME CLIMATIC EVENTS INCREASE IN FREQUENCY. OUR GROUP HAS DEMONSTRATED THAT IUHS CAUSES A LIFETIME OF POOR HEALTH AND WELFARE FOR PIGS AND HAVE DEVELOPED AN EFFECTIVE MODEL TO STUDY AND CHARACTERIZE HEAT TOLERANCE WITH A MULTIDISCIPLINARY PERSPECTIVE. GENOMIC SELECTION IS A PROMISING IUHS MITIGATION STRATEGY, GIVEN ITS PERMANENT AND CUMULATIVE GAINS OVER GENERATIONS. THIS PROJECT WILL ADDRESS THE SIGNIFICANT KNOWLEDGE GAP OF HEAT STRESS TOLERANCE IN SWINE BY TAKING A MULTI-DIMENSIONAL ANALYTICAL APPROACH THAT INTEGRATES THE EFFECTS OFGENOMICS, EPIGENOMICS, METAGENOMICS, AND METABOLOMICSTO UNDERSTAND THE TRANSGENERATIONAL EFFECTS OF IUHS IN SWINE AND ITS MICROBIOME.THIS GOAL WILL BE ACHIEVED EFFICIENTLY, AVOIDING DUPLICATION OF EFFORTS, BY LEVERAGING CURRENT FEDERALLY FUNDED PROJECTS.THE PROPOSAL WILL HAVE TWO MAIN OBJECTIVESOBJECTIVE 1: TO QUANTIFY THE ROLE OF MICROBIOTA MATURATION IN SOWS AT A HIGH OR LOW RISK OF PRODUCING OFFSPRING DISPLAYING IUHS PHENOTYPES.OBJECTIVE 2: TO DEVELOP A TRANS-GENERATIONAL MULTI-OMICS APPROACH TO IDENTIFY GENOMIC, MICROBIOTA, EPIGENOMIC, METABOLOMIC BIOMARKERS, THAT ENABLE IDENTIFYING SOWS AT MINIMAL RISK OF PRODUCING OFFSPRING WITH IUHS LEVERAGING PHENOTYPES FROM A BEHAVIORAL AND PHYSIOLOGICAL MODEL IN GENETICALLY-DIVERGENT ANIMALS.RESULTS FROM THE CURRENT PROPOSAL WILL PROVIDE A COMPREHENSIVE UNDERSTANDING OF THE MECHANISMS UNDERLYING THE TRANSGENERATIONAL EFFECTS OF IUHS, DEVELOP BIOMARKERS TO BE USED TO PRIORITIZE VARIANTS IN GENOMIC SELECTION AND HELP IDENTIFYING, AT AN EARLY STAGE, ANIMALS THAT COULD BE MORE AFFECTED BY TRANSGENERATIONAL IUHS EFFECTS; THUS ALLOWING BETTER MANAGEMENT PRACTICES TO REDUCE NEGATIVE IMPACT OF IUHS.