LARGE LITTERS IN COMMERCIAL BREEDING HERDS OFTEN INCREASE THE BIRTH OF RUNT PIGLETS. THIS REPRESENTS MAJOR CONSTRAINT TO IMPROVING REPRODUCTIVE EFFICIENCY AND PROFITABILITY IN SWINE PRODUCTION ENTERPRISES. ASYNCHRONOUS DEVELOPMENT BETWEEN UTERUS AND CONCEPTUS (EMBRYO/FETUS AND ITS EXTRA-EMBRYONIC MEMBRANES) LIMITS SURFACE AREA OF PLACENTATION AT MATERNAL-CONCEPTUS INTERFACE, COMPROMISES CONCEPTUS DEVELOPMENT AND RESULTS IN LOW-BIRTH-WEIGHT PIGLETS WITH POOR SURVIVAL IN THE NEONATAL PERIOD OF LIFE. THUS, UNDERSTANDING FUNDAMENTAL ROLES OF CONCEPTUS- AND UTERINE-SECRETED FACTORS THAT GOVERN CONCEPTUS-UTERINE SYNCHRONY REQUIRED FOR IMPLANTATION, ESTABLISHMENT OF PREGNANCY, AND PLACENTAL EXPANSION IS PREREQUISITE FOR ULTIMATELY DEVELOPING COUNTERACTING MEASURES. HERE, WE HYPOTHESIZE THAT ADRENOMEDULLIN (ADM), A HIGHLY CONSERVED PEPTIDES AMONG MAMMALS, PLAYS A CRITICAL ROLE IN THE CONTROL OF UTERINE CAPACITY AND CONCEPTUS DEVELOPMENT IN PIGS. OUR OBJECTIVE IS TO UTILIZE RNA INTERFERENCE TECHNOLOGY TO KNOCKDOWN THE ADM RECEPTOR CALCRL TO DETERMINE THE IMPACT OF ADM ON IN VITRO CELL BEHAVIORS OF PORCINE TROPHECTODERM (PTR; FUTURE PLACENTA), AND EARLY EMBRYONIC DEVELOPMENT AND SURVIVAL IN VIVO. COMPLETION OF THIS RESEARCH WILL FILL A MAJOR GAP IN OUR KNOWLEDGE OF ADM FUNCTION IN CONCEPTUS DEVELOPMENT AND SURVIVAL IN PIGS. WE ANTICIPATE THAT THE OUTCOMES WILL PROVIDE STRONG SUPPORT FOR A FUTURE STANDARD GRANT PROPOSAL, ADDRESSING THE MOLECULAR MECHANISMS BY WHICH ADM REGULATES UTERINE CAPACITY AND CONCEPTUS DEVELOPMENT, THEREBY IMPROVING REPRODUCTIVE EFFICIENCY AND PROFITABILITY IN SWINE PRODUCTION ENTERPRISES.