PROPER PLACENTAL DEVELOPMENT AND FUNCTION IS ABSOLUTELY CRITICAL FOR EMBRYO AND FETAL DEVELOPMENT AND SURVIVAL, AS WELL ASPOSTNATAL HEALTH. IN THIS PROPOSAL INNOVATIVE APPROACHES AND NEW ANIMAL MODELS WILL BE USED TO STUDY GENE FUNCTION IN THE PLACENTA AND IDENTIFY THE ROLE OF THE PROTEIN HISTONE LYSINE DEMETHYLASE (KDM) 1A IN PLACENTAL FORMATION AND FUNCTION. THE OBJECTIVES OF THIS PROPOSAL ARE (1) TO DEMONSTRATE THAT KDM1A BINDS ESTROGEN AND ANDROGENHORMONE RECEPTORS, ANDIS NECESSARY FOR PLACENTAL CELL PROLIFERATION, (2) TO DEMONSTRATE THAT KDM1A FUNCTION IS NECESSARY FOR NORMAL PREGNANCY, AND (3) DEMONSTRATE THATMATERNAL METABOLIC CHANGES CAN NEGATIVELY IMPACT KDM1AFUNCTION IN THE PLACENTA.COMPLETION OF THE PROPOSED OBJECTIVES WILL ESTABLISH A CRITICAL ROLE FOR KDM1A AND STEROID HORMONE SIGNALING IN PLACENTAL DEVELOPMENT AS WELL AND FUNCTION. THIS KNOWLEDGE IS IMPORTANT ANDULTIMATELY WILL GREATLY BENEFITANIMAL AGRICULTURE ANDHUMAN BIOMEDICINE.