THE PURPOSE OF THIS PROJECT IS TO STUDY A FETAL OVERGROWTH SYNDROME, WHICH AFFLICTS HUMANS AND CATTLE. THE HUMAN SYNDROME IS KNOWN AS BECKWITH-WIEDEMANN SYNDROME AND THE SYNDROME IN CATTLE IS KNOWN AS LARGE OFFSPRING SYNDROME. THIS SYNDROME IS MORE LIKELY TO OCCUR IN CHILDREN AND CATTLE CONCEIVED BY THE USE OF ASSISTED REPRODUCTION. THE OBSERVABLE CHARACTERISTICS OF THIS SYNDROME AT BIRTH INCLUDE LARGE PROTRUDING TONGUES, UMBILICAL HERNIAS, ABDOMINAL WALL DEFECTS CAUSING THE ORGANS TO REMAIN OUTSIDE OF THE ABDOMEN, BODY ASYMMETRY, EAR MALFORMATIONS, AND LOW BLOOD SUGAR. IN HUMANS, BWS CHILDREN HAVE AN INCREASED OCCURRENCE OF KIDNEY AND LIVER TUMORS. ONCE DIAGNOSED WITH THIS SYNDROME, CHILDREN WILL UNDERGO BLOOD DRAWS EVERY SIX WEEKS UNTIL THEY ARE FOUR YEARS OLD AND ULTRASOUNDS EVERY THREE MONTHS UNTIL THEY ARE EIGHT YEARS IN ORDER TO DETECT AND TREAT DEVELOPING TUMORS. IN CATTLE, CESAREAN SECTION IS OFTEN REQUIRED TO ASSIST WITH BIRTH OF THE LOS CALF AND AT TIMES, THE CALF DIES BECAUSE OF THE MALFORMATIONS. WE WILL TEST THE HYPOTHESIS THAT OUR EXPERIMENTAL APPROACH WILL PROVIDE MOLECULAR SIGNATURES DESCRIPTIVE OF THIS FETAL OVERGROWTH SYNDROME. OUR LONG-TERM GOAL IS TO DEVELOP INTERVENTIONS TO PREVENT OR AMELIORATE THE CHARACTERISTICS OBSERVED IN THIS CONDITION AND TO DETERMINE WHY THE USE OF ASSISTED REPRODUCTION INCREASES ITS INCIDENCE IN THE OFFSPRING. THE MAIN GOAL OF THIS PROPOSAL IS TO IDENTIFY THE MOLECULAR SIGNATURES EXPLANATORY OF THE SYNDROME, ITS DEVELOPMENT AND PROGRESSION, ITS ORGAN MALFORMATIONS, AND ITS TUMOR DEVELOPMENT. IN ORDER TO ACCOMPLISH OUR GOAL, WE WILL PRODUCE CONTROL AND LOS BOVINE FETUSES, NEONATES AND ADULTS. WE WILL COLLECT TISSUES FROM THESE ANIMALS AND PERFORM MOLECULAR ANALYSIS THAT WILL BE USED TO DECIPHER THE FORMATION AND PROGRESSION OF THE SYNDROME. OUR FINDINGS IN CATTLE WILL BE IMMEDIATELY COMMUNICATED TO OUR COLLABORATOR WHO SPECIALIZES IN BWS AT CHILDREN'S HOSPITAL OF PHILADELPHIA IN ORDER TO DETERMINE IF OUR FINDINGS INCATTLE MAY SERVE TO IMPROVE DIAGNOSTICS OF THESE PATIENTS. AT PRESENT, VERY LITTLE INFORMATION EXISTS AS TO WHY THIS SYNDROME OCCURS AND AT WHAT POINT DURING EMBRYONIC OR FETAL DEVELOPMENT THE SYNDROME DEVELOPS. OUR WORK WILL PROVIDE INFORMATION NECESSARY TO FILL THIS GAP IN KNOWLEDGE. DEVELOPMENT OF THERAPEUTIC AND PREVENTATIVE TREATMENTS FOR FETAL OVERGROWTH CONDITIONS IS NOT POSSIBLE WITHOUT KNOWING THE MOLECULAR ETIOLOGY AND PROGRESSION OF THE SYNDROME. BOTH AGRICULTURE AND HUMAN HEALTH WILL BENEFIT FROM OUR FINDINGS.