Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies

Abstract

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

Congenital Anomalies Programmed by Maternal Diabetes and Obesity on Offspring of Rats

“…Before pregnancy, there was no significant difference in fertility rates among the groups. In the experimental model of mild diabetes induction, used in the present study, the fertility rate was around 90%, corroborating Sinzato et al ( 2021 ). In the groups that consumed HS/HF diet, the treatment time was not enough to change the fertility rate.…”

Maternal Diabetes and Postnatal High-Fat Diet on Pregnant Offspring

“…We prioritize female rats because our research group studies the transgenerational effects related to pregnancy. The excess pups were euthanized by decapitation ( Sinzato et al, 2021 ).…”

“…All samples were stored at −80°C until further analysis. Uterine horns, ovaries, newborns, and placentas were removed and weighed for evaluation of maternal reproductive performance, birth weight classification, and placental efficiency ( Sinzato et al, 2021 ). Visceral fat pads from the abdominal cavity (periovarian, periuterine, perirenal, and retroperitoneal) were pooled and weighed to calculate the relative fat weight (grams of total visceral fat/100 g of body weight).…”

“…The ovaries were used to count the number of corpora lutea as an indirect parameter to assess the number of oocytes. The uterus of pregnant rats was dissected to count the number of living and dead fetuses, resorptions (embryonic deaths), and implantation sites ( Sinzato et al, 2021 ). When the implantation sites were visually undetectable, the Salewski (1964) reagent was used as a dye.…”

“…When the implantation sites were visually undetectable, the Salewski (1964) reagent was used as a dye. The percentage of embryonic loss before implantation (preimplantation loss rate), the percentage of embryonic loss after implantation (postimplantation loss rate), and the classification of the birth weight into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) were made according to Sinzato et al (2021) .…”