**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CURRENTLY FEW EFFECTIVE OR COST EFFECTIVE METHODS EXIST FOR THE REGULATION/ SYNCHRONIZATION OF ESTROUS CYCLES IN FEMALE PIGS, AND THUS THE RATIONALE FOR THIS STUDY IS TO IDENTIFY NOVEL DRUGS AND/OR APPROACHES TO BE USED FOR THIS PURPOSE. THE GOAL FOR THE CURRENT PROJECT IS TO IMPROVE OUR UNDERSTANDING OF HOW IMMUNE CELLS CONTROL OF THE CORPUS LUTEUM (CL; OVARIAN STRUCTURE THAT PRODUCES THE HORMONE PROGESTERONE, WHICH CONTROL ESTROUS CYCLES), AND THUS REVEAL/IDENTIFY NOVEL TARGETS FOR ESTROUS CYCLE REGULATING DRUGS. THERE IS AN ABUNDANT EVIDENCE IN THE LITERATURE INDICATING THAT IMMUNE CELLS SUCH AS MACROPHAGES PLAY KEY ROLES IN THE CONTROL OF THE CORPUS LUTEUM (CL), AND OUR PRELIMINARY DATA SUGGESTS THAT THE HORMONE PROGESTERONE PLAYS A CRITICAL ROLE IN REGULATING THEM. THUS THE OVERARCHING HYPOTHESIS FOR THIS PROPOSAL IS THAT PROGESTERONE ACTS VIA ITS RECEPTOR (PGR) TO INHIBIT CL MACROPHAGES AND THAT THIS PROCESS PLAYS A KEY ROLE IN THE CONTROL OF THE CORPUS LUTEUM DURING THE ESTROUS CYCLE IN THE PIG. OUR OBJECTIVES FOR THIS STUDY ARE TO 1) MEASURE THE LEVELS OF PROGESTERONE RECEPTORS IN MACROPHAGES ISOLATED FROM THE CORPUS LUTEUM (CL) ON DIFFERENT DAYS OF THE ESTROUS CYCLE, 2) DETERMINE THE EFFECT OF BLOCKING PROGESTERONE SYNTHESIS AND PROGESTERONE RECEPTORS (USING CHEMICAL INHIBITORS) ON CL MACROPHAGES MAINTAINED IN CULTURE, AND 3) DETERMINE THE EFFECT OF BLOCKING PROGESTERONE SYNTHESIS AND PROGESTERONE RECEPTORS USING CHEMICAL INHIBITORS GIVEN TO CYCLING PIGS, ON MACROPHAGES COLLECTED FROM CL TAKEN FROM TREATED ANIMALS. WE EXPECT THAT THE DATA GENERATED FROM THIS STUDY WILL CONFIRM OUR HYPOTHESIS AND PROVIDE IRREFUTABLE EVIDENCE THAT PROGESTERONE PLAYS A VITAL ROLE IN REGULATING CL MACROPHAGES, AND THAT THESE IMMUNE CELLS IN TURN ARE OF CRITICAL IMPORTANCE TO THE CONTROL OF ESTROUS CYCLICITY IN THE FEMALE PIG.THESE STUDIES WILL PROVIDE CRITICAL NEW DATA THAT WILL BE USED TO REVEAL/IDENTIFY NOVEL APPROACHES AND/OR DRUG THERAPIES FOR REGULATING AND SYNCHRONIZINGESTROUS CYCLES IN FEMALE PIGS. THE AVAILABILITY AND USE OF NOVEL DRUGS/APPROACHES TO ESTROUS CYCLE SYNCHRONIZATION IN FEMALE PIGS WOULD IMPROVE THE EFFICIENCY OF BREEDING PROTOCOLS WITHIN, AND WOULD HAVE SIGNIFICANT ECONOMIC BENEFITS FOR, THE SWINE INDUSTRY IN THE US AND OTHER COUNTRIES WORLDWIDE.