Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies)

The neonatal abnormalities, treatments and outcomes in a group of 13 cloned transgenic calves and fetuses that progressed into the third trimester of pregnancy are described. From these 13 fetuses, 8 calves were born live, 4 stillborn fetuses were recovered from 3 cows that died 7 d to 2 mo before t erm, and 1 aborted fetus was recovered at 8 mo gestation. All fetuses and c alves were derived from the same male fetal Holstein fibroblast cell line t ransfected with a beta-galactosidase marker gene. Six calves were delivered by Cesarian section and two by vaginal delivery between 278 and 288 d of g estation. Birth weights ranged from 44 to 58.6 kg. Five of the 8 live born calves were judged to be normal within 4 h of birth based on clinical signs and blood gas measurements. One of these 5 calves died at 6 wk of age from a suspected dilated cardiomyopathy. Three of the 8 calves were diagnosed w ith neonatal respiratory distress immediately following birth, one of which died (at 4 d of age) as a result of pulmonary surfactant deficiency couple d with pulmonary hypertension and elevated systemic venous pressures. Simil ar Endings of chronic pulmonary hypertension were also observed in 2 of 5 f etuses. Placental edema was present in both calves that later died and in t he 2 fetuses with cardiopulmonary abnormalities. Hydrallantois occurred wit h or without placental edema in 6 cows, and only 1 calf from this group sur vived. The 6 cows without hydrallantois or placental edema produced 5 live calves and 1 aborted fetus. The cardiopulmonary abnormalities observed in t he calves and fetuses occurred in utero in conjunction with placental abnor malities, and it is likely that the cloning technique and/or in vitro embry o culture conditions contributed to these abnormalities, although the mecha nism remains to be determined. (C) 1999 by Elsevier Science Inc.