** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** REPRODUCTIVE PERFORMANCE IS CRITICAL FOR LIVESTOCK PRODUCTION SYSTEMS. THE DEVELOPMENT OF A FETUS DEPENDS ON APPROPRIATE COMMUNICATION BETWEEN THE PLACENTA AND THE MATERNAL IMMUNE SYSTEM. KNOWLEDGE OF HOW VESICLES DERIVED FROM THE PLACENTA MODULATE THE MATERNAL IMMUNE SYSTEM WILL LEAD TO THE IDENTIFICATION OF POTENTIAL TARGETS FOR THE PREVENTION OF PREGNANCY LOSSES. THE OVERALL OBJECTIVE OF THIS APPLICATION IS TO CHARACTERIZE AND INVESTIGATE THE EFFECT OF PLACENTAL VESICLES COLLECTED FROM HEALTHY PREGNANCIES OR ABORTION-PRONE PREGNANCIES ON FETAL DEVELOPMENT AND UTERINE INFLAMMATORY STATUS. THE CENTRAL HYPOTHESIS IS THAT THE PLACENTA RELEASES VESICLES THAT PLAY AN IMPORTANT ROLE IN THE COMMUNICATION BETWEEN THE FETUS AND THE MOTHER. ADDITIONALLY, WE HYPOTHESIZE THAT THE MATERNAL UTERINE ENVIRONMENT IS MODULATED DIFFERENTLY BY VESICLES DERIVED FROM HEALTHY AND ABORTION-PRONE PLACENTAS. WE HAVE A UNIQUE MODEL THAT USES PREGNANCIES PRODUCED BY ANIMAL CLONING THAT ALLOWS US TO STUDY THE ROLE OF VESICLES IN PREGNANCY LOSSES. OUR SPECIFIC AIMS ARE TO 1) DETERMINE THE DIFFERENCES IN CONTENT OF VESICLES DERIVED FROM HEALTHY PREGNANCIES AND ABORTION-PRONE PREGNANCIES; 2) DETERMINE THE EFFECT OF UTERINE INFUSION OF PLACENTAL VESICLES FROM HEALTHY PREGNANCIES ON FETAL DEVELOPMENT AND UTERINE INFLAMMATORY STATUS IN ABORTION-PRONE PREGNANCIES. WE EXPECT OUR RESULTS TO DEMONSTRATE THAT PLACENTAL VESICLES FROM HEALTHY PREGNANCIES CAN REGULATE THE INFLAMMATORY RESPONSE MOUNTED AGAINST FETUSES PRODUCED BY ANIMAL CLONING AND PROMOTE FETAL DEVELOPMENT. THESE FINDINGS ARE EXPECTED TO PROMOTE THE DEVELOPMENT OF NOVEL APPROACHES TO IMPROVE REPRODUCTIVE EFFICIENCY AND LOWER PRODUCTION COSTS IN LIVESTOCK.