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

Abstract

To investigate the effect of hypoinsulinaemia on prenatal growth, individual fetal rabbits were injected intramusculary 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 μg/g), plasma insulin levels were decreased, but by 30 days’ gestation ineither insulin nor glucose levels differed significantly from values in control fetuses. Despite only temporary hypoinsulinaemia, severe growth retardation was caused by STZ (300 μg/g estimated fetal weight), fetuses at 30 days’ gestation weighing only 58% of the mean value obtained in saline-injected controls. At 250 μg/g STZ caused growth retardation in 3 out of 8 fetuses. A higher rate (500 μg/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.

Regulation of placental nutrient transport and implications for fetal growth

“…It is also unlikely that fetal insulin indirectly promotes fetal growth via a direct influence on placental growth and functional capacity. Pancreatectomy of fetal lambs (Fowden et al 1989) and streptozotocin treatment of fetal rabbits (Fletcher & Bassett, 1986) profoundly reduced fetal growth without overt effects on placental development.…”

The role of the placenta in fetal nutrition and growth.

“…Insulin receptors have been shown to be present in placenta, and insulin stimulation of protein synthesis has been demonstrated in ovine placenta [106,172]. Insulin administration may increase fetal and placental weight; however, neither fetal pancreatectomy nor streptozotocin treatment result in reduction of placental size in proportion to fetal weight [173][174][175].…”

Effect of Hypoinsulinemia on Growth in the Fetal Rabbit

“…Previous methods for assessing the effects o f this hormone have included: altering ma ternal-fetal substrate availability [5], sup plying excess substrate directly to the fetus [14], and surgical or chemical ablation o f the fetal pancreas [6, 8,10]. These studies have shown that the fetal pancreas is functionally responsive to variations in glucose by midges tation.…”

“…In late gestation fetal lambs, ST Z injection was associated with a significant stunting o f growth, poor fetal protein accre tion and hypoinsulinemia [6]. However, in polytocous species, such as the rat, rabbit and guinea pig, the rate o f placental blood flow is thought to represent the major factor control ling fetal growth [9], In such species, studies related to isolated insulin deficiency as a cause o f fetal growth retardation have been limited and inconclusive [10],…”