Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

Abstract

BackgroundExperimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring.MethodsIn the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67): received the β-cytotoxic agent (100 mg STZ/kg body weight - sc) on the 1st day of the life; and Non-diabetic Group (ND, n = 14): received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0), female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip) at day 7 of pregnancy (2nd induction). The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term), the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP) Tests (p < 0.05).ResultsSTZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1%) and post-implantation losses (STZ = 26.1%; ND = 5.7%), reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93%) and reduced degree of development (ossification sites).ConclusionMild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.

Neonatally induced diabetes: liver glycogen storage in pregnant rats

“…These results were compatible with those found by Portha et al (1979), who were the first to describe the experimental model for mild-intensity diabetes (100 ≤ glycemia ≤ 300mg/dL) in adult life by using STZ in the neonatal period. In agreement with the present results, other studies showed that mild diabetes could be induced by STZ on the animals first day of birth (Portha and Serradas 1991;Sinzato 2009;Saito et al 2010;Iessi et al 2010). Additionally, this model could also be performed on the postnatal day 2, on the postnatal day 5 (n5-STZ) (Wang et al 1996) and on the 2 nd and 9 th days of life (Ulicná et al 1999).…”

Extracellular HSP70 levels in diabetic environment in rats

“…Nevertheless, a number of studies carried out in our laboratory found increased rates of pre-and postimplantation embryo losses and embryonic death (resorption), reduced number of live fetuses, and maternal weight gain during diabetic pregnancy. These alterations are due to metabolic changes caused by hyperglycemic peaks during pregnancy (Kiss et al 2009;Damasceno et al 2011;Iessi et al 2010;Saito et al 2010;Dallaqua et al 2012;Sinzato et al 2012). The divergent results shown in our study, which does not reinforce an effect of diabetes on the reproductive performance of rats, is possibly explained by mating time.…”

“…Experimental studies on pregnant rats with mild diabetes (120-300 mg/dL glucose levels) showed a negative impact of this disease on their reproductive performance (Saito et al 2010). In addition, diabetes causes intrauterine growth restriction (IUGR), reduces the number of corpus luteum and embryo implantation, and increases the rates of pre-and postimplantation embryo losses (Sinzato et al 2012).…”

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

“…Experimental results support the notion of hyperglycemia as a teratogen, since high glucose levels (Dienelt and Zur Nieden 2011) or maternal diabetes in vivo as well as exposure to high glucose concentration cause embryonic maldevelopment. Several studies have shown that fetuses from mild diabetic rats have a compromised intrauterine development (Saito et al 2010;Iessi et al 2010) and elevated oxidative stress, contributing to an increased incidence of skeletal and visceral malformations at birth .…”