Abstract
Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. Experimental models are still needed to investigate the mechanism responsible for these alterations. Thus, by the administration of different doses of streptozotocin (STZ) (0, 25, 30, or 35 mg/kg body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. At day 6 of pregnancy, plasma glucose was progressively higher with an increasing STZ dose, and in rats receiving the 35-mg dose, 2 subgroups were detected: some animals had plasma glucose levels above controls but below 200 mg/dL (mildly diabetic, MD), whereas others had levels above 400 mg/dL (severely diabetic, SD). At day 20 of pregnancy, the MD rats had normal glycemia, but after an oral glucose load (2 g/kg body weight), plasma glucose increased more and insulin increased less than in controls. The SD rats maintained their hyperglycemia and had a greatly impaired oral glucose tolerance. At day 20, fetuses of SD dams were fewer, weighed less, and had enhanced plasma glucose and triglycerides and decreased insulin, whereas those from MD dams did not differ from controls. At birth, newborns from MD dams had higher body weight, plasma insulin, and liver triglycerides as well as total body lipid concentrations than controls, and on day 21, remained macrosomic and showed higher plasma glucose and liver triglyceride concentrations. At 70 days of age, offspring of MD dams had impaired oral glucose tolerance but normal plasma insulin change in the case of females, whereas plasma insulin increased less in males. These alterations were manifest more in those offspring from dams that had > 50% macrosomic newborns than in those from dams that had < 50% macrosomic newborns. In conclusion, whereas our MD rats mimic the changes taking place in gestational diabetic women and show the long-term risk of macrosomia, the SD rats are more similar to uncontrolled diabetics. Thus these two rat models, obtained with moderate amounts of STZ, could be used to study the pathophysiological consequences of these different diabetic conditions.
Highlights
Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases
Whereas fetal plasma insulin appeared lower in this group than in mildly diabetic” (MD) rats, fetal plasma TGs were higher than controls (Table 2)
In addition to showing the difficulties in obtaining a moderate and dose-dependent response to STZ treatment in rats, as seen by the normalization of the response in those rats receiving the 30-mg dose subsequent to an initial hyperglycemia, the present results show that the degree of the response varies among rats after receiving the 35-mg/kg dose
Summary
Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. By the administration of different doses of streptozotocin (STZ) (0, 25, 30, or 35 mg/kg body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. Diabetes of the mother during pregnancy causes an abnormal intrauterine metabolic and hormonal milieu that results in congenital malformations and neonatal hypoglycemia [1, 2] It enhances the risk of short- and long-term postnatal disease, including macrosomia [3, 4], an increase in the frequency of insulin resistance, gestational diabetes [5, 6], and obesity [7,8,9]. In view of difficulties in obtaining an animal model of diabetic pregnancy, the present study aimed to define the dose of STZ to obtain an easy and reproducible animal model of mildly diabetic pregnancy, by administrating different doses of STZ at the onset of pregnancy in rats and studying them at different time points, and to study some of the short- and long-term pathophysiological consequences in the offspring
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