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

Diabetology & Metabolic Syndrome

Débora Cristina Damasceno¹  Janete Aparecida Anselmo-Franci⁴  Wilma De Grava Kempinas⁵  Maria Martha Bernardi³  Yuri Karen Sinzato¹  Barbara Woodside²  Ana Carolina Inhasz Kiss¹ 

[1] Laboratory of Experimental Research of Gynecology and Obstetrics, Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University (Unesp), Distrito de Rubião Júnior s/n, 18618-970, Botucatu, São Paulo, Brazil;Center for Studies in Behavioral Neurobiology, Psychology Department, Concordia University, 7141 Sherbrooke St. W., Montreal H4B 1R6 QC, Canada;Graduate Program of Environmental and Experimental Pathology and Graduate Program of Dentistry, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, São Paulo, Brazil;Laboratório de Neuroendocrinologia da Repdrodução, Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, São Paulo University, Av. do Café s/n, 14040-904, Ribeirão Preto, São Paulo, Brazil;Department of Morphology, Botucatu Biosciences Institute, São Paulo State University, Distrito de Rubião Júnior s/n, Botucatu 18618-970 São Paulo, Brazil

关键词: Reproductive function;    Behavior;    Development;    Rat;    Streptozotocin;    Mild diabetes;   

Others  :  812647
DOI  :  10.1186/1758-5996-5-61

 received in 2013-07-19, accepted in 2013-09-24,  发布年份 2013

【 摘 要 】

Background

Neonatal 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.

Methods

At 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.

Results

As 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.

Conclusions

In 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.

【 授权许可】

   
2013 Inhasz Kiss et al.; licensee BioMed Central Ltd.

【 图 表 】

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