Wistar Rat Offspring Research Articles

Assessment of body composition in Wistar rat offspring by DXA in relation to prenatal and postnatal nutritional manipulation.

This experimental study aims to investigate the impact of combinations of prenatal and postnatal food manipulation on body composition in rat offspring. On day 12 of gestation, 100 timed pregnant rats were randomized into two nutritional groups: standard laboratory and 50% starved. Pups born to starved mothers were subdivided, based on birthweight (BiW), into fetal growth restricted (FGR) and non-FGR. Pups were born on day 21, cross-fostered, then left undisturbed lactating until the 26th postnatal day when they underwent dual-energy X-ray absorptiometry (DXA) examination. Prenatally control-fed animals had a significantly greater body weight at 26 d postnatally than the prenatally starved groups, irrespective of their postnatal diet (P < 0.001). Postnatal control diet was associated with significantly increased abdominal and total fat in non-FGR compared to FGR rats (P < 0.001). non-FGR/CONTROL rats showed higher values of abdominal fat than prenatally starved animals that were starved postnatally irrespective of their birth weight (P < 0.001). Postnatal control diet significantly increased total bone mineral content (BMC), head BMC, head area, abdominal BMC in non-FGR compared to FGR rats (P < 0.001). Interaction between prenatal and postnatal nutrition affects growth, abdominal adiposity, and bone accrual in Wistar rats' offspring at 26 d of life.

Maternal Triclosan consumption alters the appetite regulatory network on Wistar rat offspring and predispose to metabolic syndrome in the adulthood.

The objectives of this study were to evaluate the effects of maternal oral exposure to the antibacterial Triclosan (TCS) during gestation and lactation on the metabolic status of the adult offspring and on the expression of main genes controlling the appetite regulatory network. Pregnant rats were fed ad-libitum with ground food + TCS (1 mg/kg) from day 14 of gestation to day 20 of lactation (n=3) or ground food (n=3). After litter reduction, 12 males and 12 females born from the TCS exposed rats (TCS, n=24) or not (Control, n=24) were used to evaluate monthly body weight, food intake, plasma levels of cholesterol, glucose and triglycerides, and the hypothalamic mRNA expression of agouti-related protein (Agrp), neuropeptide Y (Npy) and propiomelanocortin (Pomc). Body weight for rats in the TCS group was 12.5% heavier for males at 4 months (p<0.001) and 19% heavier for females at 8 months (p=0.01). Food intake was significantly higher for rats in the TCS group at 5 months of age (p<0.01). Cholesterol and glucose levels were significantly higher for rats in the TCS group at 8 months (p<0.05). mRNA expression of Npy and Agrp were significantly increased in hypothalami of rats in the TCS group at 2 months for males or 8 months for females (p<0.05). In conclusion, low doses of oral TCS consumption by the pregnant and lactating dam increase the hypothalamic expression of the orexigenic neuropeptides Npy and Agrp in the offspring and alter their metabolic status during adulthood, resembling development of the metabolic syndrome.

Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring

Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.

Maternal hyperglycemia at different stages of gestation and its effects on male reproductive functions in rats.

The critical period during which maternal hyperglycemia predisposes offspring to develop reproductive disorders in adult life is not known. The relationship between maternal hyperglycemia at different stages and reproductive functions of male offspring was investigated. A single intraperitoneal injection of alloxan (90 mg/kg body weight) was administered at gestation days (GD) 1, 8 and 15. Animals were subsequently given 10% glucose solution daily as drinking water until parturition. All male pups were sacrificed on the 63rd day of postnatal life. Birth weight, anogenital distance index (AGDi), testes descent day, preputial separation day, sperm profile, serum testosterone, luteinizing hormone and follicle-stimulating hormone levels and the histology of the testis were assessed. Data significance test was based on 95% confidence interval. GD1 pups showed a significant increase in mean birth weight, whereas GD8 pups and GD15 pups had significantly reduced birth weight as compared with control. AGDi was significantly increased in GD8 and GD15 pups. Testes descent and preputial separation in all the experimental groups were significantly earlier. There was a significant reduction in sperm count and viability in GD8 offspring. Sperm motility was reduced in all test groups. Testosterone level was reduced in all test groups. Histology of the testis showed varying degrees of pathologies. It was deduced from this study that maternal hyperglycemia caused alterations in reproductive functions in male offspring of Wistar rats irrespective of the period of gestation involved, although GD8 pups were most severely affected.

High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring

High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake.

The influence of experimental gestational diabetes on expression of Aire mRNA and character of differentiation of Foxp3+ - cells in mesenteric lymph nodes in the offspring.

Background. Formation of immunological tolerance to self-antigens is an important mechanism that prevents development of the autoimmune diseases. Objective. With the help of molecular genetic and immunofluorescence techniques to investigate the effects of experimental gestational diabetes on the level of mRNA expression of autoimmune regulator Aire and differentiation features of Foxp3+ cells in mesenteric lymph nodes in the offspring of Wistar rats. Methods. To determine the level of Аire mRNA RT-PCR was performed in real-time by thermocycler CFX96™ Real-Time PCR Detection Systems («Bio-RadLaboratories, Inc», USA). The relative level of gene expression were studied with rat reference genes GAPDH by the method ΔΔCt. Statistical analysis were conducted using available software «Bio-Rad СFX Manager 3.1» (Bio-Rad, USA). The immunopositive Foxp3+-lymphocytes were determined using an indirect immunofluorescence technique with using a monoclonal rat antibody. Results. The offspring of experimental gestational diabetes rats showed the reduction of autoimmune regulator Aire mRNA in 2,3-8,1 times (p &lt;0,05) in mesenteric lymph node cells compared to control animals. The observed decrease in the transcriptional activity of Aire is accompanied by reduction in the number of regulatory Foxp3+ lymphocytes in mesenteric lymph node in the offspring of rats with experimental gestational diabetes, as well as reduction of concentration of the transcription factor Foxp3 in lymphocytes of cortical plateau. Conclusion. The revealed changes evidence the abuse of formation of peripheral immunological tolerance and can trigger the development of autoimmune disease in the offspring of mothers with experimental gestational diabetes.

A gestational diet high in fat-soluble vitamins alters expression of genes in brain pathways and reduces sucrose preference, but not food intake, in Wistar male rat offspring.

High intakes of multivitamins (HV) during pregnancy by Wistar rats increase food intake, body weight, and characteristics of the metabolic syndrome in male offspring. In this study, high-fat soluble vitamins were fed in combination during gestation to test the hypothesis that they partially account for the effects of the HV diet. Pregnant Wistar rats (14-16/group) were fed a recommended multivitamin diet (1-fold all vitamins) or high-fat soluble vitamin diet (HFS; 10-fold vitamins A, D, E, and K) during pregnancy. Offspring body weight, food intake, and preference as well as expression of selected genes in the hypothalamus and hippocampus were evaluated at birth, weaning, and 14 weeks postweaning. Body weight and food intake were not affected but sucrose preference decreased by 4% in those born to dams fed the HFS gestational diet. Gene expressions of the hypothalamic anorexogenic pro-opiomelanocortin (Pomc) and orexogenic neuropeptide Y (Npy) (∼30% p = 0.008, ∼40% p = 0.007) were increased in weaning and adult rats, respectively. Hippocampal dopaminergic genes (35%-50% p < 0.05) were upregulated at birth and 14 weeks postweaning. DNA hypermethylation (2% p = 0.006) was observed in the dopamine receptor 1 (Drd1) promoter region. We conclude that a gestational diet high in vitamins A, D, E, and K does not show the effects of the HV diet on body weight or food intake but may affect the development of higher hedonic regulatory pathways associated with food preference.

Influence of trans fat on skin damage in first-generation rats exposed to UV radiation.

The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders.

Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.

Tenofovir during pregnancy in rats: a novel pathway for programmed hypertension in the offspring.

To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy. Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed. Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion. This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.

Chronic maternal vitamin B12 restriction induced changes in body composition & glucose metabolism in the Wistar rat offspring are partly correctable by rehabilitation.

Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers from conception or parturition and their offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with control males. Six each of pregnant B12R dams were rehabilitated from conception and parturition and their offspring weaned to control diet. While offspring of six B12R dams were weaned to control diet, those of the remaining six B12R dams continued on B12R diet. Biochemical parameters and body composition were determined in dams before mating and in male offspring at 3, 6, 9 and 12 months of their age. Dietary vitamin B12 restriction increased body weight but decreased LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams. Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%, basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12 months age, B12R offspring had higher (than controls) fasting plasma glucose, insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic enzyme activities were increased. B12R offspring had increased oxidative stress and decreased antioxidant status. Changes in body composition, glucose metabolism and stress were reversed by rehabilitating B12R dams from conception, whereas rehabilitation from parturition and weaning corrected them partially, highlighting the importance of vitamin B12 during pregnancy and lactation on growth, muscle development, glucose tolerance and metabolism in the offspring.

Structural Changes in the Subnuclei of the Parabrachial Complex in Rats with Serotoninergic System Deficiency during Prenatal Development

Experiments were performed on the offspring of female Wistar rats (n = 8) given parachlorophenylalanine on day 16 of pregnancy to decrease endogenous serotonin levels in the offspring. Histological, immunocytochemical, and morphometric methods were used in rat pups on days 10 and 14 of postnatal development (5–6 individuals at each time point) for studies of the dorsal and ventral subnuclei of the lateral part of the parabrachial complex. The results showed that serotonin deficiency led to changes in the structure of these subnuclei. The population of large, multipolar neurons in the ventral subnucleus was found to be more sensitive to decreased serotonin levels. Experimental animals showed decreases in the body sizes of these neurons by a factor of 1.6 compared with controls, with virtually no change in the number of cells in this population. The morphological characteristics of small neurons corresponded to those in controls, though there was a reduction in the number of cells, which may explain the rarefaction of neurons in this nucleus. In the dorsal subnucleus of experimental animals, neurons of both of the populations in this structure underwent more marked changes. The sizes of both large and smaller neuron cell bodies decreased significantly, by factors of 2.0 and 1.8 respectively; the cytoplasmic volumes of these cells decreased compared with controls; the numbers of cells in both populations remained largely unaltered. Reactions detecting glial fibrillary acidic protein showed increases in the numbers of the astrocyte glial population in the early postnatal period in the experimental animals.

Inhibition of Na+,K+-ATPase in the hypothalamus, pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism

Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na+,K+-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions’ AChE and Mg2+-ATPase were recorded. The observed Na+,K+-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na+,K+-ATPase activity as a consistent neurochemical marker within the context of a systematic comparative study of existing (and novel) simulation approaches to congenital and early age hypothyroidism.

Role of methyl group vitamins in hypothalamic development of food intake regulation in Wistar rats

High multivitamin diets (HV; 10-fold AIN-93G) fed during pregnancy to Wistar rats produce offspring with increased food intake, obesity, and characteristics of metabolic syndrome. The hypothesis that methyl group vitamins in HV gestational and pup diets modify expression of the obesogenic phenotypes in the offspring through their effects on hypothalamic feeding pathways was tested by 4 studies. In studies 1 and 2, dams were fed the AIN-93G diet with recommended vitamin (RV), HV, high methyl vitamins (10-fold folate, vitamin B12 and vitamin B6) (HMethyl), or HV with normal folate (HVNF) and male offspring were weaned to a high-fat diet for 8 weeks. In studies 3 and 4, dams were fed RV, HV, or high 10-fold folate (HFol), and male offspring were weaned to RV, HV, or HFol diets for 29 weeks. The results were as follows: (i) HV and HMethyl diets increased obesogenic phenotypes and altered hypothalamic regulation of food intake and metabolism concurrent with epigenetic effects on gene expression. (ii) Removing folate additions to the HV diet showed that folate contributes to the obesogenic phenotype in the offspring and epigenetic alterations in the hypothalamus that favour increased food intake. (iii) Matching pup diet vitamin content with that of the HV and HFol diet-fed dams prevented their increased food intake, body weight, and insulin resistance when weaned to the RV diet. (iv) Both HFol gestational and pup diets altered hypothalamic feeding pathways through DNA methylation, showing that epigenetic effects of these vitamins occur not only in utero but also postnatally. In conclusion, methyl group vitamins in HV gestational and pup diets modify expression of the obesogenic phenotypes and hypothalamic food intake regulatory systems in the Wistar rat offspring.

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism.

Morphological alteration of seminiferous tubules of testes of Wistar rat offspring exposed to alcohol during pregnancy and/or lactation

This paper presents the effects of alcohol on the morphology of seminiferous tubules of testes of Wistar rat offspring exposed to alcohol during pregnancy and/or lactation. Seventy five adult female Wistar rats divided into 3 groups of 25 each and their offsprings were used. The offspring of group 1 served as control, those of group 2 were exposed to 2 g/kg body weight of 30% ethanol (v/v) during pregnancy and lactation (APL) while those of group 3 were exposed to the same dose of ethanol during lactation only (AL). At Day (D) 7, 14, 21, 35 and 49 of postnatal life, 5 male offspring were randomly selected from the three groups and sacrificed. After the sacrifice, the two testes were dissected out and then prepared for routine histological evaluation. The result of the study showed that the seminiferous epithelia of the testes of the alcohol-exposed groups were characterized by few adluminal as well as defoliated germ cells. The result further showed significant reduction (P&lt;0.05) in the diameter of the seminiferous tubules of the testes in alcohol-exposed groups. This histomorphometric effects which persisted into adulthood may have implications on the fertility of male offspring of dams who abuse alcohol during pregnancy and/or lactation.Keywords: Alcohol, pregnancy, lactation, testes, histomorphometry, Wistar rats

Prenatal exposure to integerrimine N-oxide impaired the maternal care and the physical and behavioral development of offspring rats

Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6–20 (during organogenesis and fetal development period) at doses of 3, 6 and 9mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring.

Folate in a high multivitamin gestational diet causes obesogenic phenotype and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring (271.3)

High multivitamin (HV, 10‐fold AIN‐93G) gestational diets fed to Wistar rats produce offspring with higher food intake, obesity and characteristics of metabolic syndrome. The objective was to determine if folate within the HV diet contributes to obesogenic phenotype through epigenetic effects on hypothalamic regulatory mechanisms. Male offspring of dams fed HV diet with normal folate (NF) (HVNF) were compared with those from HV fed dams. Offspring were weaned to a high fat diet for 8 weeks. HVNF offspring had lower food intake (5%, P=0.0005), body weight (4%, P=0.03), fat preference (12%, P=0.02), adiposity index (10%, P=0.04), plasma leptin concentration (24%, P=0.03), glucose response to a glucose load (18%, P&lt;0.05) and insulin resistance (12%, P=0.03). They had higher pro‐opiomelanocortin (POMC; 38%, P&lt;0.05) and lower leptin receptor (Ob‐Rb; 10%, P=0.03), mammalian target of rapamycin (MTOR; 7%, P=0.01), serotonin receptor (5‐HTR) 1A (11%, P=0.03) and 5‐HTR2A (21%, P=0.03) gene expression. DNA methylation of 5‐HTR1A (P=0.0007) was lower but higher in 5‐HTR2A (P=0.01). Phosphoinositide 3‐kinase (PI3K) signaling protein expression was improved (42%, P=0.03). In conclusion, folate in the HV gestational diet contributes to the obesogenic phenotype in the offspring concurrent with alterations in gene expression, DNA methylation and energy sensing in the hypothalamus that favor increased food intake.Grant Funding Source: Supported by Canadian Institutes of Health Research, Institute of Nutrition, Metabolism and Diabetes

Psychobiological assessment in offspring of Wistar rats supplemented with sodium selenite during the period of pregnancy and lactation (684.13)

The objective of this study was to evaluate the possible occurrence of behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. Two groups were treated during pregnancy and lactation with: saline or sodium selenite at a dose of 1 mg/kg through oral route. Thyroid status was determined by serum analysis of thyroid hormones and for gene expression analyzes, we used RT‐qPCR. At 60 days‐old, the offspring underwent a behavioral assessment in an open field test, elevated plus maze test, object recognition task and swimming forced test for five minutes. Statistical analysis was performed by t student test, considering the significant differences between means at p &lt;0.05. According to the results, it was demonstrated that supplementation with Se causes increased levels of triiodothyronine (25%, p = 0.0001) and the expression of type 2 deiodinase in brown adipose tissue (351%, p = 0.002). Moreover, Se treatment promotes reduction of TPH2 expression (12%, p = 0.007), but increases the levels of mRNA for TH (200%, p = 0.002) in the hippocampus. It was also found that the offspring of females supplemented with Se have higher locomotor activity (50%, p = 0.004) and more rearing (77%, p &lt;0.0001) in the open field test. In the elevated plus maze, the treated group had higher time spent in the open arms (143%, p = 0.005). Finally, through the object recognition task, the programmed offspring had a higher absolute index of discrimination (230%, p = 0.02). The results demonstrate that maternal supplementation with sodium selenite affects the physiological systems involved with learning and expression of affective behavior in adulthood. Therefore, we believe that the behavioral profile observed can be related to neurochemical changes during the critical period of the central nervous system ontogeny.Grant Funding Source: FAPERJ/CNPq

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na+,K+-ATPase and Mg2+-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner.