Evaluation of neonatally-induced mild diabetes in rats: Maternal and fetal repercussions

Many experimental studies have been performed to evaluate mild diabetes effects. However, results are divergent regarding glycemia and insulin measurement, fetal macrossomia, and placental weights. The aim was to investigate repercussions of neonatally-induced mild diabetes on the maternal organism and presence of congenital defects in their offspring in other mild diabetes model. On the day of birth, female offspring were distributed into two groups: Group streptozotocin (STZ): received 100 mg STZ/kg body weight, and Control Group: received vehicle in a similar time period. Maternal weights and glycemias were determined at days 0, 7, 14 and 21 of pregnancy. At day 21 of pregnancy, the rats were anesthetized and a laparotomy was performed to weigh and analyze living fetuses and placentas. The fetuses were classified as small (SPA), appropriate (APA) and large (LPA) for pregnancy age. Fetuses were also analyzed for the presence of external anomalies and processed for skeletal anomaly and ossification sites analysis. Statistical significance was considered as p < 0.05. In STZ group, there was increased glycemia at 0 and 14 days of pregnancy, lower weights throughout pregnancy, higher placental weight and index, an increased proportion of fetuses classified as SPA and LPA, and their fetuses presented with an increased frequency of abnormal sternebra, and absent cervical nuclei, which were not enough to cause the emergence of skeletal anomalies. Thus, this study shows that mild diabetes altered fetal development, characterized by intrauterine growth restriction. Further, the reached glycemia does not lead to any major congenital defects in the fetuses of streptozotocin-induced mild diabetic rats

Animal models for clinical and gestational diabetes: maternal and fetal outcomes

<p>Abstract</p> <p>Background</p> <p>Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of <it>Wistar </it>rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans.</p> <p>Methods</p> <p>On day 5 of life, 96 female <it>Wistar </it>rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight.</p> <p>Results</p> <p>Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses.</p> <p>Conclusion</p> <p>Experimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes.</p

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

<p>Abstract</p> <p>Background</p> <p>Experimental 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.</p> <p>Methods</p> <p>In 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).</p> <p>Results</p> <p>STZ 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).</p> <p>Conclusion</p> <p>Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.</p

Influence of maternal periuterine and periovarian fat on reproductive performance and fetal growth in rats

Abstract We aimed to evaluate how high-fat diet consumption can interfere with rat reproductive performance and fetal development. High-fat diet (HFD) was initiated in 30-day-old rats, distributed into two groups (n=7 animals/group): Rats receiving a standard diet and rats receiving HFD. At adulthood, the rats were mated, and on day 21 of pregnancy, the females were anesthetized, decapitated, and submitted to laparotomy to obtain visceral and periovarian adipose tissue. The uterine horns were exposed for analysis of maternal reproductive performance. The fetuses and placentas were weighed and analyzed. Pearson’s correlation test was used, and p<0.05 was considered significant. There was a significant positive correlation (HFD consumption x increased periovarian fat) and a negative correlation with the implantation, live fetus numbers and lower litter weight. Furthermore, the increased relative weight of periuterine fat was related to the lower number of live fetuses and litter weight. Regarding the fetal weight classification, there was a negative correlation between the relative weight of periovarian fat and the percentage of fetuses appropriate for gestational age and large for gestational age. Therefore, our findings show that HFD maternal intake negatively influenced on reproductive performance and fetal growth

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effects of cigarette smoke exposure before pregnancy on diabetic rats and their offspring development.</p> <p>Methods</p> <p>Diabetes was induced by streptozotocin and cigarette smoke exposure was conducted by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Diabetic female Wistar rats were randomly distributed in four experimental groups (n minimum = 13/group): nondiabetic (ND) and diabetic rats exposed to filtered air (D), diabetic rats exposed to cigarette smoke prior to and into the pregnancy period (DS) and diabetic rats exposed to cigarette smoke prior to pregnancy period (DSPP). At day 21 of pregnancy, rats were killed for maternal biochemical determination and reproductive outcomes.</p> <p>Results</p> <p>The association of diabetes and cigarette smoke in DSPP group caused altered glycemia at term, reduced number of implantation and live fetuses, decreased litter and maternal weight, increased pre and postimplantation loss rates, reduced triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA. Besides, these dams presented increased SOD and GSH-Px activities. However, the increased antioxidant status was not sufficient to prevent the lipid peroxidation observed in these animals.</p> <p>Conclusion</p> <p>Despite the benefits stemming from smoking interruption during the pregnancy of diabetic rats, such improvement was insufficient to avoid metabolic alterations and provide an adequate intrauterine environment for embryofetal development. Therefore, these results suggest that it is necessary to cease smoking extensive time before planning pregnancy, since stopping smoking only when pregnancy is detected may not contribute effectively to fully adequate embryofetal development.</p

Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

Objective: To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation.Research design and methods: One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM) positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT) in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH), gestational DM (GDM) or overt DM (DM). Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin.Results: Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a post-mortem phenomenon.Conclusion: Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus