IN RUMINANTS, ENDOMETRIAL ACTION OF PROGESTERONE IS IMPORTANT FOR ESTROUS CYCLE AND ESTABLISHMENT OF PREGNANCY. DYSREGULATION OF SPATIAL AND TEMPORAL EXPRESSION OF PROGESTERONE RECEPTOR-B (PR-B) IN THE ENDOMETRIAL CELL TYPES LEADS TO IRREGULAR ESTROUS CYCLE, PREGNANCY LOSS, AND INFERTILITY. IN RUMINANTS, LOSS OF PR-B IN THE ENDOMETRIAL LE CELLS DURING MID-LUTEAL PHASE OF THE ESTROUS CYCLE IS THE KEY MECHANISM THAT ALLOWS DEVELOPMENT OF LUTEOLYTIC MECHANISM AND THUS PROVIDES OPPORTUNITY FOR NEW ESTROUS CYCLE AND PREGNANCY [1, 3]. THE OBJECTIVE OF THE PROPOSED RESEARCH IS TO IDENTIFY AND ESTABLISH THE EPIGENETICS MECHANISMS THAT REGULATE TEMPORAL AND SPATIAL EXPRESSION OF PR-B IN THE ENDOMETRIAL LE CELLS DURING THE ESTROUS CYCLE IN RUMINANTS. SUCCESSFUL COMPLETION OF THE RESEARCH DESCRIBED IN THIS PROPOSAL WILL PROVIDE NOVEL INFORMATION OR MECHANISMS ON EPIGENETIC REGULATION OF PR-B IN THE ENDOMETRIAL LE CELLS DURING LUTEOLYSIS IN SHEEP AND IT COULD BE EXTRAPOLATED TO COWS. IT WILL PROVIDE NEW MOLECULAR AND EPIGENETICS BASE KNOWLEDGE THAT WILL FILL THE SUBSTANTIAL GAP IN OUR UNDERSTANDING OF PR-B REGULATION IN THE ENDOMETRIAL LE CELLS IN RUMINANTS. SUCH FUNDAMENTAL KNOWLEDGE IS REQUIRED FOR DEVELOPING NEW STRATEGIES TO TARGET PR-B SIGNALING IN ENDOMETRIAL LE CELLS AND TREAT INFERTILITY AND IMPROVE REPRODUCTIVE EFFICIENCY IN RUMINANTS AND OTHER AGRICULTURALLY IMPORTANT ANIMALS. THIS NEW FUNDAMENTAL INFORMATION COULD BE USED AS GUIDELINE TO STUDY THE PR-B REGULATION IN EVENTS ASSOCIATED WITH ESTABLISHMENT OF PREGNANCY IN RUMINANTS. REGARDLESS, FUNDAMENTAL KNOWLEDGE FROM THE PROPOSED RESEARCH WILL BE USED TO DETERMINE THE DIRECTION AND FOCUS OF SUBSEQUENT TRANSLATIONAL RESEARCH. IN THIS WAY, OUR PROPOSED RESEARCH ENHANCES LONG-TERM VIABILITY AND COMPETITIVENESS OF THE FOOD PRODUCTION AND IMPROVES THE PRODUCTIVITY AND SUSTAINABILITY OF THE AMERICAN AGRICULTURAL SYSTEM AND ECONOMY.