IN LIVESTOCK PRODUCTION, ALTERED FETAL GROWTH CAN HAVE SIGNIFICANT NEGATIVE IMPACTS ON THE SURVIVAL OF THE NEWBORN IN ADDITION TO MANY LONG-TERM CONSEQUENCES, SUCH AS SMALLER OFFSPRING, POOR FEEDLOT PERFORMANCE AND FERTILITY, AND REDUCED MEAT QUALITY. A COMMON CATEGORY OF ALTERED FETAL GROWTH THAT CAN CREATE THESE PROBLEMS IS IUGR: INTRAUTERINE GROWTH RESTRICTION. IUGR HAS DIRECTLY RESULTED IN PREGNANCIES WITH HIGHER INCIDENCES OF NEWBORN DEATHS AND/OR PROBLEMS WITH THE CONSEQUENCES ALREADY MENTIONED IN ADDITION TO FUNCTIONAL PLACENTAL INSUFFICIENCY. THE PLACENTA IS RESPONSIBLE FOR EXCHANGE OF NUTRIENTS (SUCH AS GLUCOSE AND AMINO ACIDS) BETWEEN THE FETUS AND THE DAM, IN ADDITION TO TRANSPORTING OXYGEN, OTHER GASES AND WASTE PRODUCTS. AS SUCH, THE PLACENTA IS AN IMPORTANT REGULATOR OF FETAL GROWTH. ADDITIONALLY, GLUCOSE IS THE PRIMARY ENERGY SOURCE FOR BOTH THE PLACENTA AND THE FETUS TO GROW DURING PREGNANCY. OUR LAB IS THEREFORE INTERESTED IN INVESTIGATING WHETHER A LACK OF PLACENTAL EXCHANGE OF GLUCOSE BETWEEN THE FETUS AND THE DAM WOULD RESULT IN AN IUGR PREGNANCY. UNDERSTANDING THE MECHANISMS OF HOW GLUCOSE TRANSPORT ACROSS THE PLACENTA COULD BE USED IN THE FUTURE FOR POTENTIAL THERAPIES IN COMPROMISED PREGNANCIES.TWO MAJOR GLUCOSE TRANSPORTERS IN THE PLACENTA ARE SLC2A1 AND SLC2A3. TO ADDRESS THE RELATIVE IMPORTANCE OF BOTH, OUR LAB HAS DEVELOPED SLC2A1 AND SLC2A3 DEFICIENT PREGNANCIES USING A COMPREHENSIVE GENE-TARGETING APPROACH. THIS PROPOSAL AIMS TO TEST THE CENTRAL HYPOTHESIS THAT THAT SLC2A1 DEFICIENCY WILL HAVE A GREATER IMPACT ON FETAL GROWTH THAN DOES SLC2A3 DEFICIENCY. TO TEST THIS HYPOTHESIS, WE PROPOSE TWO SPECIFIC AIMS: SPECIFIC AIM 1 WILL GENERATE, VALIDATE AND USE SLC2A1 DEFICIENT PREGNANCIES FOR HARVESTING AT 75 DAYS OF GESTATION FOR ANALYSIS AND TESTING WHETHER SLC2A1 DEFICIENCY RESULTS IN IUGR AT MID-GESTATION. SPECIFIC AIM 2 WILL COMPARE THE IMPACTS OF SLC2A1 AND SLC2A3 DEFICIENCIES AT MID-GESTATION USING VARIOUS ANALYTICAL METHODS, INCLUDINGINVESTIGATING THE GENETICS OF PLACENTAL AND FETAL METABOLISM PATHWAYS AFFECTED (RNASEQ). THIS PROPOSAL IS SIGNIFICANT BECAUSE IT ADDRESSES MAJOR KNOWLEDGE GAPS IN UNDERSTANDING MECHANISMS AND GENES INVOLVED WITH PLACENTAL INSUFFICIENCY. GIVEN THE CRITICAL NEED FOR ADEQUATE NUTRITION DURING PREGNANCY AND HOW LARGE A ROLE GLUCOSE TRANSPORT PLAYS IN THAT, IS WORK WILL EXPAND OUR KNOWLEDGE OF IUGR PATHOLOGY AND ITS IMPACTS ON PLACENTAL AND FETAL METABOLISM. THIS PROPOSAL WILL ADVANCE THE FIELD BY PROVIDING INSIGHTS INTO HOW WE MAY IMPROVE IUGR PREGNANCY OUTCOMES AND FETAL SUCCESS IN THE FUTURE. THIS PROJECT IS HIGHLY RESPONSIVE TO THE GOALS OF AFRI EDUCATION AND WORKSHOP DEVELOPMENT AS IT SUPPORTS THE GOAL: 1): SATISFY HUMAN FOOD AND FIBER NEEDS; AS MANY LIVESTOCK SUCCUMB TO MORBIDITIES AND MORTALITIES BROUGHT ABOUT BY IUGR PREGNANCIES WHICH REDUCE RED MEAT PRODUCTION. BY ADDRESSING CURRENT GAPS IN KNOWLEDGE REGARDING THE PATHOLOGY OF IUGR WITH THIS PROPOSED RESEARCH, WE WILL SUPPORT DEVELOPMENT OF FUTURE THERAPEUTIC APPROACHES TO AMELIORATING AND/OR POTENTIALLY RESCUING AT-RISK OFFSPRING SO MORE HEALTHY ANIMALS CAN ENTER PRODUCTION. IMPROVEMENT OF OFFSPRING SURVIVAL AND LIFELONG HEALTH (AND THEREFORE PRODUCTIVITY) ALSO DIRECTLY ADDRESSES THE GOAL 4): SUSTAIN THE ECONOMIC VIABILITY OF FARM OPERATIONS; WHICH WILL ALLOW THE PRODUCER MORE RETURN ON THEIR INVESTMENT BY IMPROVING HERD SURVIVAL. WE ARE ALSO ADDRESSING THE GOAL 5): ENHANCE THE QUALITY OF LIFE FOR FARMERS AND SOCIETY AS A WHOLE; BY CONTRIBUTING TO FOOD SECURITYTHROUGH IMPROVED PRODUCTIVITY AND SURVIVAL OF LIVESTOCK. FINALLY, THIS PROPOSAL IS RESPONSIVE TO BOTH THE ANIMAL NUTRITION, GROWTH AND LACTATION (A1231) AND ANIMALREPRODUCTION (A1211) PROGRAM AREAS, SINCE SUCCESSFUL FETAL GROWTH IS SO TIGHTLY INTERCONNECTED WITH POSTNATAL SURVIVAL, GROWTH, AND PRODUCTION TRAITS. LASTLY, MY SPECIFIC AIMS ARE ALSO HIGHLY RESPONSIVE TO THE PREDOCTORAL FELLOWSHIP PROGRAM AREA (A7101), IN THAT THEY OUTLINE A PARADIGM FOR COMPREHENSIVE MENTORSHIP, IMPLEMENTATION OF GOAL-DRIVEN EVALUATION PLANS, AND FOSTER MY DEVELOPMENT AS A PART OF THE NEXT GENERATION OF RESEARCH SCIENTISTS. THE PROPOSED STUDY WILL ALSO SUPPORT MY EDUCATION GOALS DURING MY PHD PROGRAM WHICH INCLUDE GAINING BOTH PROJECT LEADERSHIP AND TECHNICAL SKILLS IN MY FIELD OF INTEREST. THESE EXPERIENCES WILL CONTRIBUTE TO OUR FIELD THROUGH SCIENTIFIC PRESENTATIONS, PEER-REVIEWED MANUSCRIPTS, BUT ALSO TRANSLATIONAL KNOWLEDGE FOR THE PRODUCER, AS WELL AS ENABLE ME TO EVENTUALLY DEVELOP MY OWN HIGH-IMPACT RESEARCH PROGRAM IN THE FUTURE.