Glucose homeostasis in pregnant rats submitted to dietary protein restriction

In the present work, we examined the effects of feeding a low protein diet during pregnancy on glucose-induced insulin secretion and glucose homeostasis in rats. Young (60 days), pregnant (P) or non-pregnant (NP) rats were fed during pregnancy or for 21 days (the NP) a normal (17%) or a low (6%) protein diet. Serum glucose and insulin levels and pancreas insulin content in the fed state; total area under serum glucose curve (AG) after a glucose load and serum glucose disappearance rate (Kitt) after insulin administration; as well as 86Rb outflow, 45Ca uptake and insulin secretion by isolated pancreatic islets in response to glucose were evaluated. Serum glucose was lower in 17%-P (12%) and 6%-P (27%) than in corresponding NP-rats. Serum insulin was higher in 17%- P (153%) and 6%-P (77%) compared to the corresponding NP-rats. Pancreatic insulin was higher in 6%-rats (55%) than in 17%-rats. No differences were found in AG among the groups whereas Kitt was lower in 6%-NP and higher in 6%-P than in the equivalent 17% rats. Increasing glucose concentration from 2.8 to 16.7 mmol/l, reduced 86Rb outflow from isolated islets from all groups. Increasing glucose concentration from 2.8 to 16.7 mmol/l elevated 45Ca uptake by 17%-NP (47%), 17%-P (40%) and 6%-P (214%) islets but not by 6%-NP ones. The increase in 45Ca uptake was followed by an increase in insulin release by the 17%-NP (2767%), 17%-P (2850%) and 6%-P (1200%) islets. In conclusion, 6%-P rats show impaired glucose induced insulin secretion related to reduced calcium uptake by pancreatic islets. However, the poor insulin secretion did not fully compensate the high peripheral sensitivity to the hormone, resulting in hypoglycemia.

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

Background: This study was undertaken to test the hypothesis that diabetes and pregnancy detrimentally affect the normal function of urethral striated muscles in rats, providing a model for additional studies related to urinary incontinence. The aim of this study was to evaluate morphological alterations in the urethral striated muscles of diabetic pregnant rats. Materials and Methods: Twenty female Wistar rats were distributed into four experimental groups of five rats as follows: virgin, pregnant, diabetic virgin, and diabetic pregnant. Diabetes was induced using streptozotocin administration (40 mg/kg i.v.). The rats were lethally anesthetized, and the urethra and vagina were extracted as a unit. Cryostat sections (6 μm thick) were cut and stained with hematoxylin-eosin, and immunohistochemical procedures were performed and subjected to morphological and semi quantitative analysis. Results: The urethral striated muscle from the diabetic pregnant rats presented with the following variations: thinning and atrophy, disorganization and disruption associated with the colocalization of fast and slow fibers and a steady decrease in the proportion of fast vs slow fibers. Conclusion: Diabetes and pregnancy impair the urethral striated muscle and alter its fiber type distribution. © Copyright G. Marini et al., 2011.

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

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R∈=∈0.5908, P∈=∈0.0024; R∈=∈0.4877, P∈=∈0.0134, respectively) and the number of malformations per fetus (R∈=∈0.6103, P∈=∈0.0015; R∈=∈0.4875, P∈=∈0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R∈=∈0.3887, P∈=∈0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R∈=∈0.3999, P∈=∈0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes. © 2012 Cell Stress Society International.

Urethral striated muscle and extracellular matrix morphological characteristics among mildly diabetic pregnant rats: translational approach

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Impact of chronic stressors on the anxiety profile of pregnant rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Different intensities of exercise (swimming) applied to pregnant rats: maternal and fetal outcomes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Circulating thyroid hormone levels in young pregnant rats and their fetuses: Effect of malnutrition

In order to evaluate some factors likely to be involved in the maternal and fetal growth impairment due to alimentary protein deficiency, the circulating levels of triiodothyronine (T 3) and thyroxine (T 4) were studied in 4 young (45-day-old) female rat groups: control and malnourished, both nonpregnant and pregnant; similarly schedules groups were studied using adult (100-day-old) rats. Circulating levels of T 4 were higher in nonpregnant, malnourished young rats in their corresponding controls. T 3 levels were higher in young malnourished animals and lower in adult malnourished animals, nonpregnant or pregnant, as compared to controls. Pups from young malnourished mothers showed significantly lower birth weights than those from controls. The present results suggest that there are age differences in thyroid function, as affected by protein-calorie malnutrition in pregnant and non-pregnant rats. On the other hand, the circulating thyroid hormone levels were not importantly affected by the mother dietary protein restriction under our experimental conditions.

Zinc metabolism in pregnant and lactating rats and the effect of varying iron: Zn in the diet

Pregnant rats were given control (46 mg iron/kg, 61 mg zinc/kg), low-Zn (6.9 mg Zn/kg) or low-Zn plus Fe (168 mg Fe/kg) diets from day 1 of pregnancy. The animals were allowed to give birth and parturition times recorded. Exactly 24 h after the end of parturition the pups were killed and analysed for water, fat, protein, Fe and Zn contents and the mothers' haemoglobin (Hb) and packed cell volume (PCV) were measured. There were no differences in weight gain or food intakes throughout pregnancy. Parturition times were similar (mean time 123 (SE 15) min) and there were no differences in the number of pups born. Protein, water and fat contents of the pups were similar but the low-Zn Fe-supplemented group had higher pup Fe than the low-Zn unsupplemented group, and the control group had higher pup Zn than both the low-Zn groups. The low-Zn groups had a greater incidence of haemorrhaged or deformed pups, or both, than the controls. Pregnant rats were given diets of adequate Zn level (40 mg/kg) but with varying Fe:Zn (0.8, 1.7, 2.9, 3.7). Zn retention from the diet was measured using 65Zn as an extrinsic label on days 3, 10 and 17 of pregnancy with a whole-body gamma-counter. A group of non-pregnant rats was also included as controls. The 65Zn content of mothers and pups was measured 24-48 h after birth and at 14, 21 and 24 d of age. In all groups Zn retention was highest from the first meal, fell in the second meal and then rose in the third meal of the pregnant but not the non-pregnant rats. There were no differences between the groups given diets of varying Fe:Zn level. Approximately 25% of the 65Zn was transferred from the mothers to the pups by the time they were 48 h old, and a further 17% during the first 14 d of lactation. The pup 65Zn content did not significantly increase after the first 20 d of lactation but the maternal 65Zn level continued to fall gradually.

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. on d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

The onset of oestrus and ovulation in lactating rats

Lactation delays the re-initiation of oestrous cyclicity in rats, resulting in physiological sterility for the duration of suckling. During this phase, the secretion of pituitary gonadotrophins is suppressed by an unknown mechanism. Continued application of the suckling stimulus by litter replacement (Bruce, 1958; Nicoll & Meites, 1959), or injections of prolactin (Meites & Nicoll, 1959), have been shown to prolong lactation considerably beyond the usual period. The present study aimed to demonstrate the role of prolactin in inhibiting the gonadotrophin secretion necessary for the re-establishment of oestrous cyclicity during lactation. Pregnant rats weighing approximately 300 g were obtained from the Institute colony and housed in individual cages. At parturition, the number of young in the litter was adjusted to eight, two or one as required. The day following the post-partum oestrus was regarded.

UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression

Bromati CR, Lellis-Santos C, Yamanaka TS, Nogueira TC, Leonelli M, Caperuto LC, Gorjao R, Leite AR, Anhe GF, Bordin S. UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression. Am J Physiol Regul Integr Comp Physiol 300: R92-R100, 2011. First published November 10, 2010; doi:10.1152/ajpregu.00169.2010.-Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in beta-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2 alpha phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in beta-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in beta-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4/CHOP-induced TRB3 expression.

Semen parameters, fertility and testosterone levels in male rats exposed prenatally to betamethasone

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Adult partner preference and sexual behavior of male rats exposed prenatally to betamethasone

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)