Effect of Streptozotocin on Foetal Lambs in Mid-pregnancy

Abstract

Streptozotocin was administered to 11 foetal lambs in utero at 70-85 days of gestation. Four of the foetuses survived and, when delivered at 134-142 days, exhibited significant growth retardation of the trunk and delayed osseous maturation in limb bones. The foetal kidneys and livers were most affected, but in three of the four foetuses, the weight of the brain was appropriate for gestational age. Likewise head size, measured by length or biparietal diameter, was normal. The insulin content of the foetal pancreas was less after streptozotocin-treatment than in normal animals of a similar gestation. Two streptozotocin-treated foetuses, catheterized at 120 days gestation, had higher glucose concentrations and lower insulin responses than in controls when infused with glucose .. Plasma concentrations of ovine placental lactogen were lower in streptozotocin-treated foetuses than in controls, but serum somatomedin-like activity measured by receptor assay was greater than in controls. When the foetal serum was chromatographed on Sephadex G150 at acid pH, the major increase in somatomedin-like activity was found in the smaller molecular weight fraction (molecular size about 10000). The foetal growth retardation associated with streptozotocin administration in mid-pregnancy may be due to insulin deficiency, but the normal brain weight which occurred suggests that some other factor (possibly a somatomedin) regulates the growth of this organ.