Effects Of STZ Neonatal Administration on Maternal Glucose Tolerance in Different Reproductive States

Abstract

Background: Rodent models of diabetes during pregnancy have the potential to yield useful insights into maternal and offspring outcomes as well as their underlying mechanisms. Maternal mild hyperglycemia, which better resembles human gestational diabetes, can be induced by administering streptozotocin (STZ) in the neonatal period. Although STZ neonatal injection is a well-established experimental model to induce mild hyperglycemia, there are no studies focusing on the stability of this phenotype across different reproductive states. Objective: The aim of the present study was to compare the effects of STZ neonatal administration on maternal glucose tolerance in cycling, pregnant and lactating rats. Methods: Newborn female rats from the same litter were assigned either to Control (n=11) or STZ condition (STZ 100 mg/kg in 100 microliters citrate buffer subcutaneous; n=11). One Control and one STZ treated female from each litter were used in this study. Oral glucose tolerance tests (OGTT) were performed in adulthood prior to mating (postnatal day 75), on pregnancy day 17, and 10 days after their litter was weaned. Glycemic changes during the OGTT were evaluated by estimation of the total area under the curve (AUC). Results: In both Control and STZ groups the glycemic curve changed across reproductive states probably reflecting metabolic adaptations to these states. Neonatal STZ treatment resulted in a higher AUC relative to controls at all three timepoints but the size of this increase varied with reproductive states. Conclusion: The degree of glucose intolerance demonstrated in female rats that received STZ as newborns varies across reproductive state.