** 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 PIGS, A SIGNIFICANT NUMBER OF EMBRYOS THAT WILL EVENTUALLY BECOME PIGLETS DIE DURING PREGNANCY. TWENTY TO 40 PERCENT OF THESE EMBRYOS DIE DURING THE FIRST 20 DAYS OF PREGNANCY WHEN THESE EMBRYOS ARE DEVELOPING WITHIN THE INNER CAVITY OF THE UTERUS. THIS CAVITY LACKS NORMAL LEVELS OF OXYGEN AND CONTAINS NUTRIENTS THAT ARE RELEASED INTO THE CAVITY BY THE UTERUS THAT FEED THE EMBRYOS. THE GOAL OF THIS STUDY IS TO BETTER UNDERSTAND HOW THE NUTRIENTS RELEASED BY THE UTERUS ARE USED BY THE EMBRYOS IN THIS DIFFICULT ENVIRONMENT THAT LACKS OXYGEN. SUCH KNOWLEDGE CAN HELP US TO DEVELOP STRATEGIES TO DECREASE THE NUMBER OF EMBRYOS THAT DIE, AND IN TURN INCREASE PROFITABILITY TO THE FARMER WHO RAISES PIGS FOR MARKET. THE SUGARS GLUCOSE AND FRUCTOSE ARE ESSENTIAL FOR THE GROWTH, DEVELOPMENT AND MAINTENANCE OF CELLS, TISSUES, ORGANS AND WHOLE ORGANISMS. MANY CELLS CHANGE GLUCOSE AND FRUCTOSE METABOLISM TO ADAPT TO ENVIRONMENTS LACKING IN OXYGEN. GLUCOSE AND FRUCTOSE ARE THE MAJOR NUTRIENTS RELEASED INTO THE UTERINE CAVITY TO FEED THE DEVELOPING EMBRYOS IN PIGS, AND OUR PRELIMINARY WORK SUGGESTS THAT THE EARLY DEVELOPING PLACENTAE OF EMBRYOS USE GLUCOSE AND FRUCTOSE TO SUPPORT EMBRYO GROWTH AND SURVIVAL. THE LONG-TERM GOALS OF THIS RESEARCH ARE TO UNDERSTAND MECHANISMS WHEREBY GLUCOSE AND FRUCTOSE ACTIVATE NUTRIENT-SENSING PATHWAYS IN PORCINE EMBRYOS AND PLACENTAE UNDER THE STRESS OF LOW OXYGEN LEVELS IN THE UTERINE CAVITY. THE SPECIFIC OBJECTIVES ARE TO DETERMINE IF PORCINE CONCEPTUSES (1) RESPOND TO THE STRESS OF LOW OXYGEN THROUGH METABOLIC CHANGES THAT LEAD TO THE EXPRESSION OF ENZYMES INVOLVED IN GLYCOLYTIC METABOLISM TO PROVIDE PRECURSORS FOR THE ONE-CARBON METABOLIC PATHWAY AND (2) UTILIZE THE POLYOL PATHWAY/FRUCTOLYSIS TO BYPASS FEEDBACK INHIBITION OF GLYCOLYSIS TO MAINTAIN A FUNCTIONING ONE-CARBON METABOLIC PATHWAY.