Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Abstract

BackgroundNeonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood.MethodsAt birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data.ResultsAs expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered.ConclusionsIn female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.

Acción de la estreptozotocina en un modelo experimental de inducción neonatal de la diabetes

“…En la rata adulta la inoculación de diferentes dosis de este agente causa una deficiencia casi total de insulina y, por lo tanto, niveles elevados de hiperglucemia que simulan la diabetes de tipo 1 (1,3,7). Sin embargo, varios autores refieren que una única dosis elevada de estreptozotocina (100 mg/kg), administrada durante los primeros días de vida del conejo, provoca un déficit de insulina moderado y valores medios de hiperglucemia semejantes a los de la diabetes de tipo 2 en el transcurso de las siguientes semanas (1,2,6,8).…”

“…En numerosos estudios se plantean diferentes momentos (días 0, 2 o 5 de nacidos) y vías de inoculación (subcutánea, intraperitoneal o intravenosa) del fármaco (3,6,8,9), sin embargo, no existen informes sobre las ventajas de uno u otro protocolo con relación a las características de la enfermedad una vez se desarrolla en el animal adulto.…”

Propolis improves pregnancy outcomes and placental oxidative stress status in streptozotocin-induced diabetic rats

“…However, foetal blood glucose was significantly improved when treated with propolis or insulin without significant change in foetal body weight. The reduction in foetal birth weight in diabetes may be associated with the detrimental effect of maternal hyperglycaemia leading to intrauterine growth retardation [ 25 , 26 ]. However, both foetal blood glucose and foetal body weight were significantly improved in DM + Combined group which could be attributed to the improved maternal FBG and weight.…”

Introduction for the special issue on “exercise during pregnancy”

“…They decreased swimming time compared to previous studies to see if exercise could prevent the effects of the hyperglycemic environment in a milder model of diabetes induced in rats. When neonatal mice are exposed to a chemical isolated from a species of bacterium called streptozotocin, pancreatic beta cells die, but regenerate to some extent, resulting in a milder form of diabetes than when streptozotocin is injected into adult animals (Inhasz Kiss et al, 2013). The swimming protocol with reduced time did not improve parameters in the milder hyperglycemic environment and, in fact, caused some developmental defects in the rat fetuses.…”