Sheep fetal development at 35 days of gestation was examined following natu
ral mating, in vitro production (IVP) of fertilized embryos, or somatic cel
l nuclear transfer (NT). Five crossbred (Blackface x Black Welsh) and four
purebred (Black Welsh) fetuses and their associated placentae produced by n
atural mating were morphologically normal and consistent with each other. F
rom 10 ewes receiving 21 IVP embryos, 17 fetuses (81 %) were recovered, and
15 of these (88%) were normal. The NT fetuses were derived from two Black
Welsh fetal fibroblast cell lines (BLW1 and 6). Transfer of 21 BLW1 and 22
BLW6 NT embryos into 12 and 11 ewes, respectively, yielded 7 (33%) and 8 (3
6%) fetuses, respectively. Only three (43%) BLW1 and two (25%) BLW6 NT fetu
ses were normal, with the rest being developmentally retarded. The NT fetal
and placental deficiencies included liver enlargement, dermal hemorrhaging
, and lack of placental vascular development reflected by reduced or absent
cotyledonary structures. Fibroblasts isolated from normal and abnormal clo
ned fetuses did not differ in their karyotype from sexually conceived fetus
es or nuclear donor cell lines. Our results demonstrate that within the fir
st quarter of gestation, cloned fetuses are characterized by a high inciden
ce of developmental retardation and placental insufficiency. These deficien
cies are not linked to gross defects in chromosome number.