**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 SUCCESS IN CATTLE IS CRITICAL FOR PROFITABILITY AND SUSTAINABILITY OF BEEF AND DAIRY ENTERPRISES, AS MISSED PREGNANCY OPPORTUNITIES CAN COST PRODUCERS BETWEEN $90-1,900 DEPENDING ON THE GESTATIONAL STAGE THE PREGNANCY IS LOST. DESPITE AN 85% INITIAL FERTILIZATION RATE TO ARTIFICIAL INSEMINATION, ONLY 30% OF ANIMALS CONCEIVE AND CARRY PREGNANCY TO CALVING. THIS AMOUNTS TO A COST OF ALMOST $1 BILLION PER YEAR FROM PREGNANCY LOSSES ON BEEF AND DAIRY FARMS. PLACENTAL DEVELOPMENT, AMONG OTHER ASPECTS OF PREGNANCY, IS ESSENTIAL FOR SUCCESSFUL REPRODUCTION AS FAILURE OF CONCEPTUS (EMBRYO AND ASSOCIATED PLACENTA) IMPLANTATION AND DEVELOPMENT CAN RESULT IN LOSS OF BETWEEN 5-20% OF PREGNANCIES BETWEEN THE FIRST AND THIRD MONTHS OF GESTATION. ALTHOUGH DIFFERENCES IN GENE EXPRESSION HAVE BEEN ASSOCIATED WITH SUCCESSFUL PREGNANCY, IT IS NOT KNOWN WHAT REGULATES GENE EXPRESSION DYNAMICS IN THE PLACENTA AND HOW THIS MAY CONTRIBUTE TO EFFECTIVE REPRODUCTION. THIS PROJECT INTENDS TO FACILITATE A BETTER UNDERSTANDING OF GENOME REGULATION DURING PLACENTAL DEVELOPMENT AS IT RELATES TO FERTILITY TRAITS IN CATTLE. TO ACCOMPLISH THIS GOAL, CUTTING-EDGE GENOMIC TECHNOLOGIES WILL BE LEVERAGED TO PROFILE REGULATORY REGIONS OF THE GENOME AT SINGLE-NUCLEUS RESOLUTION AND OVERLAY GENETIC VARIATION ASSOCIATED WITH REPRODUCTIVE TRAITS TO PREDICT POTENTIAL BIOLOGICAL OUTCOMES. OBJECTIVE 1 WILL USE SINGLE-NUCLEI OPEN CHROMATIN PROFILING (ASSAY FOR TRANSPOSASE ACCESSIBLE CHROMATIN WITH SEQUENCING; ATAC-SEQ) IN THE EARLY AND MID GESTATION BOVINE PLACENTA TO DEFINE OPEN CHROMATIN AND PREDICT REGULATORY REGIONS. OBJECTIVE 2 WILL OVERLAY GENETIC VARIANTS ASSOCIATED WITH REPRODUCTIVE TRAITS WITH REGIONS PROFILED IN OBJECTIVE 1 TO PREDICT POTENTIAL BIOLOGICAL CONSEQUENCES OF THIS VARIATION. DEFINING REGULATORY ELEMENTS IN CELL POPULATIONS OF THE PLACENTA CAN ELUCIDATE THE BIOLOGICAL EFFECTS OF GENETIC VARIATION THAT RESIDE IN THESE REGIONS, AS DISRUPTION OF REGULATORY ELEMENTS SUCH AS ENHANCERS OR TRANSCRIPTION FACTOR BINDING SITES CAN INFLUENCE GENE EXPRESSION. FURTHER UNDERSTANDING GENETIC VARIATION WITHIN REGULATORY REGIONS AND HOW IT MAY INFLUENCE REPRODUCTIVE TRAITS WILL ALLOW FOR MORE PRECISE GENOMIC SELECTION STRATEGIES. THIS WILL IN TURN CONTRIBUTE TO MORE PROFITABLE AND SUSTAINABLE CATTLE OPERATIONS BY IMPROVING REPRODUTION AND REDUCING COSTLY PREGNANCY LOSSES.