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.

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

“…This shows that the varying degree of organ retardation seen is in large part related to the slower growth rate prior to 30 days' gestation, rather than a consequence of selective toxic actions of STZ. Similarly, the pattern of changes in organ sizes observed in STZ-treated fetal lambs [19] are also largely consistent with changes consequent on severe intrauterine undernutrition in sheep [20].…”

“…Brinsmead and Thorburn [19] reported similarly marked growth retardation in 4 fe tal lambs given STZ during mid-gestation. In these lambs, pancreatic insulin content and the insulin secretory response to hyperglycaemia were still depressed during late gesta tion, even though basal plasma insulin con centrations were in the normal range.…”

Glucose Suppression of Insulin Secretion in Chronically Hyperglycemic Fetal Sheep

“…The intra-and interassay variability were both < 10% over the course of these studies. At the time of necropsy, fetal and maternal pancreas tissue were placed in 0.01 N HCI and frozen at -70°C until analyzed for insulin content using methodology previously reported (13,14).…”

The Effect of Pancreatectomy on the Uptake of Metabolites by the Sheep Fetus

“…Diabetic infants or infants with pancreatic agenesis are small at birth and experimental hypoinsulinaemia -whether produced with anti-insulin sera, diabetogenic drugs or pancreatectomy -is associated with raised glucose levels in the fetus (Alexander, Britton, Cohen & Nixon, 1970;Schiff, Colle & Stern, 1972;Sherwood, Chance & Hill, 1974;Felix & Jacquot, 1976;Brinsmead & Thorburn, 1982;Fowden & Comline, 1984). Short-term insulin deficiency in utero has also been shown to reduce glucose uptake by the tissues of the fetal rat but there have been few studies of the long-term effects of hypoinsulinaemia on glucose uptake by the fetus (Rabain & Picon, 1974).…”