ABSTRACT
Placental and fetal liver blood perfusions are reduced in intrauterine growth-restricted human fetuses. We hypothesized that changes in fetal liver blood supply can alter fetal growth. In nine ewes with twin pregnancies at a gestational age of 119+/-2 days, a stent (4 mm) was placed into the ductus venosus of one twin (DV(stent) group). Alternatively, in 17 near term sheep with twin (n=11) or singleton (n=6) pregnancies, a DV was blocked with an embolization coil (DV(coil) group) for about one week. The cell proliferation rate (pKi-67) was determined in the liver, heart, skeletal muscle, kidneys and placenta. The dilatation or occlusion of the DV did not change placental perfusion on the first day or later after surgery. The liver blood supply was decreased in the DV(stent) group by more than half from 499+/-371 to 278+/-219 ml min(-1) (mean+/-s.d., n=4), and increased two-fold in the DV(coil) group (P< 0.05). The percentage of liver/body weight was decreased from 3.9+/-0.6 per cent in control twin to 3.0+/-0.2 per cent (n=3) in the DV(stent) group. Occlusion of the DV lead to an increase in the percentage of liver/body weight from 3.4+/-0.8 per cent to 4.3+/-0.8 per cent (n=11, P< 0.05). Reduced liver blood supply in the DV(stent) group was associated with a decrease of cell proliferation in the liver from 12.43+/-2.31 to 6.5+/-0.62 (nuclei microm(2) 10(-4), n=3, P=0.058), in heart from 1.14+/-0.03 to 0.93+/-0.02 (nuclei microm(2) 10(-4), P< 0.05), and in skeletal muscle from 0.82+/-0.05 to 0.54+/-0.01 (nuclei microm(2) 10(-4), P< 0.05). The increased liver blood perfusion following occlusion of the DV increased cell proliferation sixfold in the liver, (n=9, P< 0.005) and twofold in heart muscle, skeletal muscle and the kidneys (P< 0.05), whereas no significant difference was seen in the placenta. The expression of mRNA for IGF-I and IGF-II in the liver was increased in the DV(coil) group. In conclusion, these results suggest that liver blood perfusion can regulate fetal growth.
