**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CATTLE ARE A MAJOR SOURCE OF FOOD PROTEIN, MILK AND ECONOMIC GAIN IN THE UNITED STATES AND MANY OTHER COUNTRIES AROUND THE WORLD. REPRODUCTIVE FAILURE, HOWEVER, IS A MAJOR LIMITATION IN CATTLE PRODUCTION AS IT REDUCES THE NUMBER OF CALVES BORN. MOST REPRODUCTIVE FAILURE IS THE RESULT OF EARLY EMBRYONIC MORTALITY, A POORLY UNDERSTOOD PHENOMENON WHERE THE EMBRYO FAILS TO SURVIVE WITHIN THE FIRST 28 DAYS OF GESTATION. FURTHER, COW EMBRYOS PRODUCED BYIN VITROMETHODS [IN VITROFERTILIZATION (IVF) ORIN VITROPRODUCTION (IVP)], A TECHNOLOGY USED TO PRODUCE CALVES WITH HIGHER QUALITY GENETICS, ARE MORE LIKELY TO SUCCUMB TO EARLY EMBRYONIC MORTALITY COMPARED TO EMBRYOS THAT ARE CONCEIVED WITHIN THE REPRODUCTIVE TRACT (IN VIVOEMBRYO DEVELOPMENT). LIMITATIONS IN CURRENT IVP EMBRYO CULTURE CONDITIONS, WHICH DO NOT EFFECTIVELY MIMIC THE OVIDUCT OR UTERUS, LIKELY CONTRIBUTE TO POOR IVP BOVINE EMBRYO QUALITY. DATA FROM PREVIOUS EXPERIMENTS SUGGESTS THAT IVP BOVINE EMBRYOS, COMPARED TO EMBRYOS THAT DEVELOPIN VIVO, ALTER THE LOCAL UTERINE PROTEIN AND METABOLITE ENVIRONMENT AFTER THEY ARE TRANSFERRED INTO THE UTERUS. THIS IS BASED ON THE OBSERVATION THAT IVP BOVINE EMBRYOS REDUCED GENE ACTIVITY FOR UTERINE CELL PROTEINS INCLUDING SOLUTE CARRIER (SLC) TRANSPORTERS FOR ZINC (SLC39A9), GLYCINE (SLC6A9) AND GLUTAMATE/NEUTRAL AMINO ACIDS (SLC1A4). THEREFORE, WE HYPOTHESIZE THAT IVP BOVINE EMBRYOS REDUCE LOCAL UTERINE PROTEIN AND METABOLITE CONTENT INCLUDING CONCENTRATIONS OF ZINC, GLYCINE AND GLUTAMATE COMPARED TO EMBRYOS THAT DEVELOPIN VIVO, CONTRIBUTING TO POOR EMBRYONIC DEVELOPMENT AND EARLY EMBRYONIC MORALITY IN CATTLE. IN ADDITION, WE HYPOTHESIZE THAT CULTURING IVP BOVINE EMBRYOS WITH BOVINE UTERINE CELLS WILL INCREASE IVP EMBRYO QUALITY PRIOR TO TRANSFER INTO THE UTERUS. THIS STUDY HAS THREE SPECIFIC OBJECTIVES: 1) IDENTIFY UTERINE PROTEINS AND METABOLITES LOCALLY INDUCED BY IVP BOVINE EMBRYOS COMPARED TO EMBRYOS THAT DEVELOPIN VIVO2) IDENTIFY THE BOVINE UTERINE CELL TYPE RESPONSIBLE FOR SECRETION OF THE PROTEINS AND METABOLITES AND 3) TEST FOR AN ADVANTAGE OF USING BOVINE UTERINE CELLS TO IMPROVE IVP BOVINE EMBRYO CULTURE CONDITIONS. WE EXPECT IVP BOVINE EMBRYOS TO ALTER UTERINE EPITHELIAL CELL SECRETION OF PROTEINS AND METABOLITES CONSIDERED NECESSARY FOR EMBRYONIC SURVIVAL INCLUDING ZINC, GLYCINE AND GLUTAMATE. ADDITIONALLY, WE EXPECT IVP BOVINE EMBRYO QUALITY TO INCREASE WHEN THE EMBRYO IS CULTURED WITH BOVINE UTERINE CELLS. INFORMATION PROVIDED BY THESE STUDIES MAY LEAD TO IMPACTFUL TECHNOLOGIES THAT IMPROVE IVP BOVINE EMBRYO CULTURE CONDITIONS, REDUCE EARLY EMBRYONIC MORTALITY OF BOVINE EMBRYOS AND ADVANCE PRODUCTION OF CALVES WITH HIGHER QUALITY GENETICS.
$496,000FY2020National Institute of Food and AgricultureUSDA
University Of Tennessee, Memphis TN