**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** NON-TECHNICAL SUMMARYINCREASED LITTER SIZE OF PIGS IN COMMERCIAL BREEDING HERDS HAS RESULTED IN A GREATER NUMBER LIGHTER WEIGHT PIGLETS AT BIRTH WITH COMPRISED HEALTH AND SURVIVABILITY DUE TO THE INCREASED FETAL CROWDING DURING GESTATION. ESTABLISHING THE FUNDAMENTAL ROLES OF CONCEPTUS- AND UTERINE-SECRETED FACTORS IS AN ESSENTIAL STEP TO DEVELOP STRATEGIES TO INCREASE PLACENTAL AND FETAL GROWTH TO IMPROVE OVERALL HEALTH AND SURVIVABILITY OF PIGLETS BEFORE AND AFTER BIRTH. STUDIES WILL TEST THE HYPOTHESIS THAT SPECIFIC EMBRYONIC GENES (AROMATASE AND PROSTAGLANDIN SYNTHETASE 2) ARE CRITICAL FOR PLACENTAL DEVELOPMENT AND GROWTH TO TRANSFER NUTRIENTS ESSENTIAL TO FETAL GROWTH THROUGHOUT GESTATION. OUR OBJECTIVE IS TO UTILIZE GENE EDITING TECHNOLOGY TO KNOCKOUT SPECIFIC EMBRYONIC GENES TO DETERMINE THEIR ROLE IN EARLY EMBRYONIC DEVELOPMENT AND SURVIVAL. RESEARCH IS EXPECTED TO PROVIDE CLEAR INFORMATION ON THE ROLE OF SPECIFIC EMBRYONIC GENES THAT REGULATE PLACENTAL DEVELOPMENT AND FETAL GROWTH. FUNDAMENTAL KNOWLEDGE GAINED FROM THE RESEARCH WILL BE USED TO DETERMINE THE DIRECTION AND FOCUS OF SUBSEQUENT TRANSLATIONAL RESEARCH TO IMPROVE REPRODUCTIVE EFFICIENCY OF PIGS AND THUS OVERALL PROFITABILITY OF SWINE PRODUCTION ENTERPRISES. SUCCESSFUL COMPLETION OF THE RESEARCH PLAN IS EXPECTED TO FILL A SUBSTANTIAL GAP IN OUR KNOWLEDGE OF EARLY PREGNANCY IN PIGS AND PROVIDE NOVEL INSIGHTS INTO THE BIOLOGICAL ROLES OF CONCEPTUS ESTROGENS AND PROSTAGLANDINS IN CONCEPTUS-MATERNAL INTERACTIONS AND ESTABLISHMENT OF PREGNANCY. IMPORTANTLY, FUNDAMENTAL KNOWLEDGE GAINED FROM THESE STUDIES WILL BE VERY USEFUL TO DIRECT AND FOCUS TRANSLATIONAL RESEARCH THAT IS NECESSARY TO INCREASE FERTILITY, FETAL GROWTH AND NEONATAL SURVIVABILITY IN DOMESTIC SWINE. DETERMINATION THAT PIG CONCEPTUS ESTROGEN AND PROSTAGLANDINS BOTH FUNCTION TO COMPENSATE FOR EACH OTHER IN ESTABLISHMENT AND MAINTENANCE PREGNANCY, OPENS THE QUESTION IF CONCEPTUS AND/OR UTERINE PROSTAGLANDIN E PRODUCTION IS ACTUALLY THE ACTIVE FACTOR IN CL MAINTENANCE. WE WILL CREATE AN EMBRYO DOUBLE AROMATASE (CYP19A1-/-)/PROSTAGLANDIN SYNTHETASE 2 (PGTS2-/-) KNOCKOUT TO ADDRESS THE HYPOTHESIS THAT EITHER CONCEPTUS OR ENDOMETRIAL ESTROGEN INDUCE PROSTAGLANDIN PGE PRODUCTION IS INVOLVED WITH MATERNAL RECOGNITION IN THE PIG.