** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FERTILITY IN POSTPARTUM DAIRY COWS IS IMPROVING DUE TO IMPROVEMENTS IN COW MANAGEMENT. UTERINE DISEASE IS COMMON IN POSTPARTUM COWS. DESPITE PROGRESS THE PROGRESS AND IMPROVEMENTS THAT HAS BEEN MADE IN MANYAREAS, WE HAVE NOT OVERCOME THE LARGE IMPACT THAT POSTPARTUM (AFTER CALVING) UTERINE DISEASE HAS ON THE REPRODUCTIVE SYSTEM AND FERTILITY. THE PROPOSED RESEARCH ATTEMPTS TO UNDERSTAND HOW A UTERINE DISEASE EARLY POSTPARTUM (WITHIN ONE TO TWO WEEKS AFTER CALVING) CAN PROGRAM THE UTERUS SO THAT THE COW CANNOT BECOME PREGNANT WHEN SHE IS INSEMINATED SEVERAL MONTHS AFTER CALVING. SPECIFICALLY, WE PROPOSE THAT AN ADVERSE PROGRAM IS ESTABLISHED WITHIN THE UTERUS OF A COW WITH UTERINE DISEASE AND THE UTERUS ITSELF MUST BE REPROGRAMMED TO RESTORE FERTILITY. THIS ADVERSE PROGRAMMING INCLUDES STRUCTURAL DAMAGE TO THE UTERUS (SCAR TISSUE, ETC.) ANDFUNCTIONAL DAMAGE TO THE CELLS WITHIN THE UTERUS. IN THE FUTURE THIS DAMAGE MAY BE REPAIREDTHROUGH ADVANCED THERAPEUTICS THAT REMOVE SCAR TISSUE, REDUCE PAIN AND INFLAMMATION AND REPROGRAM CELLS TO RESTORE NORMAL FUNCTION. IN THE PROPOSED STUDIES WE WILL INVESTIGATE THE ORIGINOF THE CELLS THAT REPOPULATE THE UTERUS AFTER CALVING AND THE MECHANISMS THROUGH WHICH UTERINE DISEASE ADVERSELY PROGRAMS THEIR FUNCTION. THIS NEW INFORMATION IS CRITICAL TO UNDERSTANDING THE POSTPARTUM UTERUS, HOW POSTPARTUM DISEASE LEADS TO INFERTILITY, AND HOW TO CORRECT THE PROBLEM.THEFUNDAMENTAL KNOWLEDGE CREATED THROUGH THIS RESEACH IS NECESSARY TO DEVELOP INNOVATIVE TOOLS TO RESTORE FERTILITY IN DISEASED COWS SO THAT THEY CAN BECOME PREGNANT POSTPARTUM TO LATER HAVE A CALF AND PRODUCE MILK IN A SUBSEQUENTLACTATION.THE RESTORATION OF FERTILITY AND PRODUCTION OF MILK FROM THESE COWS WILL MAINTAIN A SAFE AND PLENTIFUL SUPPLY OF DAIRY PRODUCTS TO CONSUMERS.