REPRODUCTIVE PERFORMANCE IS CRITICAL FOR LIVESTOCK PRODUCTION SYSTEMS. MOST OF LOSS IN REPRODUCTIVE EFFICIENCY IS DUE TO EMBRYONIC DEATH EARLY IN GESTATION. THE DEVELOPMENT OF A FETUS DEPENDS ON ITS ACCEPTANCE BY THE MATERNAL IMMUNE SYSTEM. KNOWLEDGE OF HOW THIS ACCEPTANCE TAKES PLACE WILL LEAD TO THE IDENTIFICATION OF POTENTIAL STRATEGIES TO PREVENT PREGNANCY LOSSES. THE CENTRAL HYPOTHESIS FOR THE PROPOSED RESEARCH IS THAT PROPER MESSAGES DELIVERED BY PLACENTA-DERIVED VESICLES ARE NECESSARY TO MODULATE THE MATERNAL IMMUNE SYSTEM DURING PREGNANCY IN CATTLE. OUR OVERALL OBJECTIVE IS TO DETERMINE THE ROLE OF PLACENTA-DERIVED VESICLES IN THE COMMUNICATION WITH THE MATERNAL IMMUNE SYSTEM TO PROMOTE ACCEPTANCE OF THE DEVELOPING FETUS. WE HAVE A MODEL FOR BOVINE PREGNANCY LOSS AND PLACENTAL MALFUNCTION THAT USES PREGNANCIES PRODUCED BY ANIMAL CLONING THAT WE CAN COMPARE WITH PREGNANCIES ESTABLISHED BY NATURAL BREEDING. CLONING IS THE PROCESS OF GENERATING A GENETIC REPLICA OF AN ANIMAL WITH A DESIRABLE TRAIT USING ITS SKIN CELLS. WE EXPECT TO FIND THAT PLACENTA-DERIVED VESICLES FROM PREGNANCIES ESTABLISHED BY NATURAL BREEDING DELIVER MESSAGES TO THE MATERNAL IMMUNE SYSTEM THAT PROMOTE THE ACCEPTANCE OF THE FETUS WHILE PREGNANCIES ESTABLISHED BY CLONING WILL FAIL TO PROMOTE THIS ACCEPTANCE RESULTING IN FETAL LOSS. THESE FINDINGS ARE EXPECTED TO PROMOTE THE DEVELOPMENT OF NOVEL APPROACHES TO IMPROVE REPRODUCTIVE EFFICIENCY AND LOWER PRODUCTION COSTS IN LIVESTOCK.