Influence of Maternal Diabetes in Rats on Hemoglobin Synthesis and Uridine Uptake by Fetal Liver Cells

The effect of streptozocin (STZ)-induced maternal diabetes in rats on fetal erythropoiesis was studied in short-term cultures of fetal liver cells at the time of switch from embryonic to adult hemoglobins. Liver erythroid cell functions were monitored by measuring the incorporation of [³H]-uridine in trichloroacetic acid (TCA)-soluble and-insoluble cell fractions and of [³H]-leucine in hemoglobin chains. Fetal liver cells of diabetic rats showed a higher incorporation of [³H]-uridine compared with controls when the cells were obtained from 14-day-old fetuses. However, there were no significant differences in the uptake of uridine when cells were obtained from 16-day-old fetuses. In parallel cell cultures, incorporation of [³H]-leucine into adult and embryonic globin chains was studied by separation of the globin chains by high-performance liquid chromatography (HPLC). The overall globin chain synthesis was higher in the fetuses of diabetic mothers compared with controls on day 14 of gestation. Erythropoietin had similar effects on the stimulation of globin chains in the two groups of fetuses. However, in the fetuses of diabetic mothers, erythropoietin had a specific stimulatory effect on embryonic-type globins that was significantly higher in the fetuses of diabetic mothers compared with controls. Differences between fetuses of control and diabetic mothers completely disappeared at 16 days of gestation. It is concluded that maternal diabetes has an effect on the cells synthesizing embryonic hemoglobins on day 14 of gestation, but by the time the switch from embryonic to adult-type hemoglobins is complete, these differences are abolished.