Effects of Streptozotocin Injection into Fetal Rabbits on Their Subsequent Growth in utero

To investigate the effect of hypoinsulinaemia on prenatal growth, individual fetal rabbits were injected intramuscularly with streptozotocin (STZ) at 23 days of gestation following surgical reduction of litter number to 4 at 9 days' gestation. Two days after giving STZ (300 micrograms/g), plasma insulin levels were decreased, but by 30 days' gestation in either insulin nor glucose levels differed significantly from values in control fetuses. Despite only temporary hypoinsulinaemia, severe growth retardation was caused by STZ (300 micrograms/g estimated fetal weight), fetuses at 30 days' gestation weighing only 58% of the mean value obtained in saline-injected controls. At 250 micrograms/g STZ caused growth retardation in 3 out of 8 fetuses. A higher rate (500 micrograms/g) caused fetal death. The extent of growth retardation caused by STZ varied amongst tissues in the conceptus. Placenta and brain were not significantly altered, but relative to the size of the placenta the kidneys and empty carcass were severely retarded. The relationship between carcass and kidney weights did not differ from that in naturally small fetuses of the same age. Protein and RNA concentrations in the carcass were not altered by STZ, but that of DNA was reduced. In the placenta, DNA concentration was increased and RNA decreased. These observations are consistent with a major effect of hypoinsulinaemia on the growth of carcass and renal tissues, though loss of a renal growth factor cannot be ruled out.