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Sample records for maternal protein-restricted rats

  1. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    PubMed Central

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J.; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M.

    2013-01-01

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 0.1 vs 6.3 0.1?g; mean SE) to weaning (42.4 1.3 vs 49.1 1.6?g), although at 16 weeks of age their body weight was similar to control (421.7 8.9 and 428.5 8.5?g). Maternal protein restriction also increased lactase activity in the proximal (0.23 0.02 vs 0.15 0.02), medial (0.30 0.06 vs 0.14 0.01) and distal (0.43 0.07 vs 0.07 0.02 Ug-1min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 1.11 vs 2.38 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 0.02 vs 0.91 0.02 Ug-1min-1) and sucrase mRNA abundance (4.48 0.51 vs 1.95 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring. PMID:23532268

  2. Retinoic acid enhances nephron endowment in rats exposed to maternal protein restriction.

    PubMed

    Makrakis, John; Zimanyi, Monika A; Black, M Jane

    2007-11-01

    A reduced nephron complement at birth renders the kidney susceptible to renal disease in adulthood. Retinoic acid (RA; the active metabolite of vitamin A) is linked to nephrogenesis in vitro and in vivo. The aim of this study was to determine the effect of administration of retinoic acid in midgestation in rats on nephron endowment in offspring exposed to maternal protein restriction. Rats were fed either a normal-protein diet (NPD) or a low-protein diet (LPD) during pregnancy and lactation. Half of the dams in the LPD group were injected intraperitoneally with retinoic acid (20 mg/kg) during gestation at embryonic day 11.5. At 4 weeks of age, the offspring were anesthetized and perfusion-fixed, and nephron number estimated using unbiased stereological techniques. Body weight and kidney volume was significantly reduced in all LPD offspring. There was a significant 29% reduction in nephron number in the LPD group compared with the NPD offspring, whereas the number of nephrons in kidneys from the LPD + RA offspring was not significantly different compared with controls. In conclusion, administration of a single bolus dose of retinoic acid during midgestation restored nephron endowment to normal in offspring exposed to maternal protein restriction. PMID:17849154

  3. Effect of maternal protein restriction in rats on cardiac fibrosis and capillarization in adulthood.

    PubMed

    Lim, Kyungjoon; Zimanyi, Monika A; Black, M Jane

    2006-07-01

    This study examines the effect of maternal protein restriction in rats on levels of cardiac fibrosis, myocardial capillarization, and media:lumen ratio of intramyocardial arteries in adult offspring. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low-protein diet (LPD; 8.7% casein) during pregnancy and lactation. Female offspring (seven per group) were weaned at 4 wk of age and grown to adulthood. At 24 wk of age, the offspring were perfusion fixed. Cardiac fibrosis and media:lumen ratio of intramyocardial arterioles was assessed using image analysis and cardiac capillarization was stereologically investigated. Body weights at 2 and 24 wk of age were significantly reduced (31% and 8%, respectively) in the LPD offspring; however, heart size was not different at 24 wk. Importantly by adulthood, there was a significant 15% increase in left ventricular interstitial fibrosis in LPD offspring. There were no differences in levels of perivascular fibrosis, myocardial capillarization, or in the media:lumen ratio of intramyocardial arteries between groups. Because cardiac fibrosis is associated with impaired cardiac contractility and arrhythmia, our results suggest that induction of interstitial fibrosis may contribute to the increased cardiac disease in adult subjects who were exposed to an adverse intrauterine environment. PMID:16690945

  4. Effect of maternal protein restriction during pregnancy and lactation on the number of cardiomyocytes in the postproliferative weanling rat heart.

    PubMed

    Lim, Kyungjoon; Zimanyi, Monika A; Black, M Jane

    2010-03-01

    Maternal protein restriction leads to a reduction in the number of cardiomyocytes in the rat heart at birth. However, in rats, cardiomyocytes continue to proliferate until about 2 weeks after birth. Hence, this study aimed to examine the effect of maternal protein restriction, on the number of cardiomyocytes in the young rat heart at a time point when the cardiomyocytes have ceased proliferating and are terminally differentiated. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low protein diet (LPD; 8.7% casein) during pregnancy and lactation. Offspring (seven males and seven females per group) were perfusion fixed at 4 weeks of age. Heart volume and total cardiomyocyte number were determined using stereological techniques. At 4 weeks of age, body weights in both male and female LPD offspring were significantly reduced compared with NPD controls whereas relative heart volumes were significantly increased in LPD offspring. Total number of cardiomyocytes was not significantly different between groups. In both groups, there was a significant linear correlation between cardiomyocyte number and heart volume. In conclusion, total cardiomyocyte number in the postproliferative rat heart does not appear to be affected by maternal protein restriction per se but is directly related to heart size. PMID:20091884

  5. Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat.

    PubMed

    Torres, Nimbe; Bautista, Claudia J; Tovar, Armando R; Ordz, Guillermo; Rodrguez-Cruz, Maricela; Ortiz, Victor; Granados, Omar; Nathanielsz, Peter W; Larrea, Fernando; Zambrano, Elena

    2010-02-01

    Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism. PMID:19920218

  6. Effect of maternal protein restriction on liver metabolism in rat offspring.

    PubMed

    Moraes, Camila; Rebelato, Hrcules J; Amaral, Maria Esmeria C; Resende, Thais Marangoni; Silva, Eduarda V C; Esquisatto, Marcelo A M; Catisti, Rosana

    2014-09-01

    Consequences of gestational protein restriction (GPR) on liver metabolism in rat offspring were investigated. Pregnant dams were divided into groups: normal (NP, 17% casein) or low-protein diet (LP, 6% casein). Livers were collected from 30-day-old offspring (d30) for analysis or isolation of mitochondria. At d30, hepatic and muscle glycogen was increased in LP group. Mitochondrial swelling and oxygen uptake (recorded with a Clark-type electrode) were significantly reduced in NP female and LP pups. Thiobarbituric acid reactive substances production was lower in females (NP or LP), suggesting significant inhibition of lipid peroxidation. Measurement of mitochondrial respiration (states 3 and 4 stimulated by succinate) showed a higher ADP/O ratio in LP pups, particularly females, suggesting higher phosphorylation efficiency. In the 1st month of life, under our experimental conditions, GPR protects liver mitochondria against oxidative stress and females seem to be more resistant or more suitable for survival. PMID:24994532

  7. Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

    PubMed Central

    Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

    2014-01-01

    Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

  8. Maternal protein restriction compromises myocardial contractility in the young adult rat by changing proteins involved in calcium handling.

    PubMed

    de Belchior, Aucelia C S; Freire, David D; da Costa, Carlos P; Vassallo, Dalton V; Padilha, Alessandra S; Dos Santos, Leonardo

    2016-02-01

    Maternal protein restriction (MPR) during pregnancy is associated with increased cardiovascular risk in the offspring in adulthood. In this study we evaluated the cardiac function of young male rats born from mothers subjected to MPR during pregnancy, focusing on the myocardial mechanics and calcium-handling proteins. After weaning, rats received normal diet until 3 mo old, when the following parameters were assessed: arterial and left ventricular hemodynamics and in vitro cardiac contractility in isolated papillary muscles. The body weight was lower and arterial pressure higher in the MPR group compared with young adult offspring of female rats that received standard diet (controls); and left ventricle time derivatives increased in the MPR group. The force developed by the cardiac muscle was similar; but time to peak and relaxation time were longer, and the derivatives of force were depressed in the MPR. In addition, MPR group exhibited decreased post-pause potentiation of force, suggesting reduced reuptake function of the sarcoplasmic reticulum. Corroborating, the myocardial content of SERCA-2a and phosphorylated PLB-Ser16/total PLB ratio was decreased and sodium-calcium exchanger was increased in the MPR group. The contraction dependent on transsarcolemmal influx of calcium was higher in MPR if compared with the control group. In summary, young rats born from mothers subjected to protein restriction during pregnancy exhibit changes in the myocardial mechanics with altered expression of calcium-handling proteins, reinforcing the hypothesis that maternal malnutrition is related to increased cardiovascular risk in the offspring, not only for hypertension, but also cardiac dysfunction. PMID:26586904

  9. Maternal protein restriction in the rat during pregnancy and/or lactation alters cognitive and anxiety behaviors of female offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Charco, R; Bautista, C J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2012-02-01

    Maternal protein deficiencies can developmentally program offspring to lifelong dysfunction of many physiological systems. We hypothesized that maternal isocaloric low protein diet during fetal and early postnatal development would negatively affect female offspring anxiety, exploration, associative learning and motivation as measured by the elevated plus maze (EPM), open field test (OFT), operant conditioning and the progressive ratio task, respectively. Control mothers (C) received a 20% casein diet and restricted mothers (R) a 10% casein diet to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second lactation diet) to enable evaluation of offspring effects influenced by maternal diet during pregnancy and lactation. Maternal protein restriction decreased open arm time and distance in RR and RC offspring, increased anxiety behavior, in the EPM. In the OFT, the RR and RC offspring displayed decreased exploration (increased stress) as indexed by decreased distance in the center zone. These behaviors in the EPM and OFT was associated with increased corticosterone levels during an immobilization test in the RR offspring with intermediary effects in the RC offspring. Learning impairment was observed in the RR, CR and RC offspring during fixed ratio 5 schedule of reinforcement. Motivational effects were measured in RR offspring responding less, decreased motivation, and CR offspring making more responses, increased motivation, than CC offspring. These findings reveal the negative effects of developmental protein restriction on female offspring behavior. The underlying basis for these negative outcomes remains to be elucidated. PMID:22023958

  10. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    PubMed

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. PMID:26763577

  11. Quercetin intake during lactation modulates the AMP-activated protein kinase pathway in the livers of adult male rat offspring programmed by maternal protein restriction.

    PubMed

    Sato, Shin; Mukai, Yuuka; Saito, Takeshi

    2013-01-01

    Quercetin, a naturally occurring flavonoid, has been reported to possess numerous biological activities including activation of adenosine-5'-monophosphate-activated protein kinase (AMPK). We investigated the effects of quercetin intake during lactation on the AMPK activation in the livers of adult offspring programmed by maternal protein restriction during gestation. Pregnant Wistar rats were fed control and low-protein diets during gestation. Following delivery, each dam received a control or 0.2% quercetin-containing control diet during lactation as follows: control on control (CC), control on restricted (LPC) and 0.2% quercetin-containing control on restricted (LPQ). At weaning (week 3), some of the pups from each dam were killed, and the remaining pups (CC, n=8; LPC, n=10; LPQ, n=13) continued to receive a standard laboratory diet and were killed at week 23. Blood chemistry and phosphorylation levels of AMPK?, acetyl-CoA carboxylase (ACC), endothelial nitric oxide synthase (eNOS) and mammalian target of rapamycin (mTOR) in the livers of male offspring were examined. At week 3, the level of phosphorylated AMPK protein in LPQ increased about 1.5- and 2.1-fold compared with LPC and CC, respectively, and the level in LPQ at week 23 increased about 1.9- and 2.9-fold, respectively. A significant increase in phosphorylated ACC and eNOS levels was found in LPQ. There was no significant difference among the three groups in the level of phosphorylated mTOR protein. In conclusion, quercetin intake during lactation up-regulates AMPK activation in the adult offspring of protein-restricted dams and modulates the AMPK pathway in the liver. PMID:22819550

  12. Maternal protein restriction induces alterations in hepatic tumor necrosis factor-?/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring

    PubMed Central

    Liu, Xiaomei; Qi, Ying; Tian, Baoling; Chen, Dong; Gao, Hong; Xi, Chunyan; Xing, Yanlin; Yuan, Zhengwei

    2014-01-01

    It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-? (TNF-?)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7?-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-? expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4? and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-?/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life. PMID:25120278

  13. Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats

    PubMed Central

    Liu, Xiaomei; Qi, Ying; Gao, Hong; Jiao, Yisheng; Gu, Hui; Miao, Jianing; Yuan, Zhengwei

    2013-01-01

    It is well recognized that intrauterine growth restriction leads to the development of insulin resistance and type 2 diabetes mellitus in adulthood. To investigate the mechanisms behind this metabolic imprinting phenomenon, we examined the impact of maternal undernutrition on insulin signaling pathway and the ATP sensitive potassium channel expression in the hypothalamus of intrauterine growth restriction fetus. Intrauterine growth restriction rat model was developed through maternal low protein diet. The expression and activated levels of insulin signaling molecules and KATP protein in the hypothalami which were dissected at 20 days of gestation, were analyzed by western blot and real time PCR. The tyrosine phosphorylation levels of the insulin receptor substrate 2 and phosphatidylinositol 3'-kinase p85? in the hypothalami of intrauterine growth restriction fetus were markedly reduced. There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. Moreover, the abundances of gluconeogenesis enzymes were increased in the intrauterine growth restriction livers, though no correlation was observed between sulfonylurea receptor 1 and gluconeogenesis enzymes. Our data suggested that aberrant intrauterine milieu impaired insulin signaling in the hypothalamus, and these alterations early in life might contribute to the predisposition of the intrauterine growth restriction fetus toward the adult metabolic disorders. PMID:23341697

  14. Gestational protein restriction alters cell proliferation in rat placenta.

    PubMed

    Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; de Sousa Righi, Eloá Fernanda; Catisti, Rosana

    2016-04-01

    We recently showed that gestational protein restriction (GPR) alters the structure of the rat placenta on day 19 of gestation (dG). The aim of the study was to investigate the spatial and temporal immunolocalization of proliferating cell antigen Ki67 in normal and GPR placental development. Pregnant Wistar rats were divided into two groups: normal (NP, 17 % casein) or low-protein diet (LP, 6 % casein). Placentas and fetus were collected and weighed at 15, 17, 19 and 21 dG. Morphological, morphometric and ultrastructural analyses were performed. Immunoperoxidase was used to identify nuclear antigen Ki67 in placental sections. We observed a significant reduction in the number of trophoblast giant cells and glycogen cells in the LP group. Placental weight was significantly reduced only at 17 dG in the LP group, in parallel to a decrease in glycogen cells. From 15 to 21 dG, the thickness of the junctional zone (JZ) decreased in NP and LP animals, while that of the labyrinth zone (LZ) increased in parallel to a reduction in the number of proliferating cells in this LZ zone. GPR significantly inhibits cell proliferation in the JZ, especially at 15 and 17 dG. The ultrastructural appearance of the cytoplasm of giant and cytotrophoblastic cells indicates degeneration from 15 to 21 dG and this effect is enhanced in LP animals suggesting early aging. Offspring of NP dams were significantly heavier than offspring of LP dams at 21 dG. GPR causes modifications in specific regions of the placenta, cell proliferation inhibition and fetal growth restriction. PMID:26779652

  15. Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study

    PubMed Central

    Petry, Clive J; Jennings, Bridget J; James, Lynwen A; Hales, Charles N; Ozanne, Susan E

    2006-01-01

    Background Previous studies have shown that in male rats, exposure to maternal protein restriction either in utero or whilst suckling can have profound effects on both longevity and kidney telomere lengths. This study monitored albuminuria longitudinally in male rats whose mothers had been protein restricted either during pregnancy or lactation. Methods Pregnant Wistar rats were fed either a 20% ('control') or an 8% protein ('low protein') diet. At two days of age some of the pups were cross-fostered to dams fed the diet that was not given to their biological mothers. At weaning all pups were fed standard chow. Urine samples were collected for the measurement of albumin and creatinine at monthly intervals from two months-of-age. Longitudinal analysis was then performed using repeated measures analysis of variance. Results Overall estimated marginal geometric mean (95 % confidence interval) urine albumin to creatinine ratios were: control animals 79.5 (57.2~110.6) g/mol (n = 6 litters, 24 animals in total), those exposed in utero to maternal protein restriction 71.0 (47.4~106.5) (n = 4 litters, 16 animals in total), those exposed to maternal protein restriction whilst suckling 21.2 (14.7~30.4) (n = 5 litters, 20 animals in total) (p < 0.001). These latter animals had lower albumin to creatinine ratios than either of the two other groups (both p < 0.001), which had ratios that were indistinguishable from each other (p = 1.0). Similar results were gained using 24 h. urine albumin excretion rates. These differences became evident from three months-of-age and were long-lasting. Conclusion Animals exposed to maternal protein restriction whilst suckling exhibited lower urine albumin excretions during much of adult life. As urine albumin can be nephrotoxic, these rats therefore appeared to be relatively protected against future nephron damage like that previously observed in animals exposed to maternal protein restriction in utero. PMID:17010194

  16. Effect of nickel sulfate on testicular steroidogenesis in rats during protein restriction.

    PubMed Central

    Das, Kusal K; Dasgupta, Shakuntala

    2002-01-01

    Nickel, a widely used heavy metal, exerts potent toxic effects on peripheral tissues as well as on the reproductive system. Low dietary protein coupled with exposure to this metal induces more severe changes, including biochemical defects, structural disorders, and altered physiologic functions. This study was designed to assess the effects of nickel sulfate on testicular steroidogenesis and to ascertain whether such alterations are reversible with normal protein and protein-restricted dietary regime. Nickel sulfate [2 mg/100 g body weight (bw)] dissolved in double-distilled water was administered on alternate days for 10 doses in a normal protein diet (18% casein) and a protein-restricted diet (5% casein) to Wistar male albino rats (bw 160 +/- 5 g). Two groups, one with a normal protein diet and the other with a protein-restricted diet, served as controls. Twenty-four hours after the last treatment, all the animals except those in withdrawal groups were sacrificed by decapitation. We observed a significant reduction in the activities of the testicular steroidogenic enzymes and plasma testosterone concentration accompanied by a significant elevation in cholesterol and ascorbic acid level in both dietary groups. After 15 days of withdrawal from the nickel sulfate treatment, the testicular steroidogenic enzymes, along with plasma testosterone level, improved significantly in both normal protein-fed and protein-restricted dietary groups. The effects of nickel on testicular cholesterol and ascorbic acid concentration were also reduced after withdrawal. Our results indicate that nickel sulfate affects the steroidogenic enzymes, causing alteration in the formation of testosterone in both dietary groups, which was manifested in the elevated cholesterol and ascorbic acid level with decreased activities of steroidogenic enzymes in adult rats testes. However, these alterations were reversible in both groups of animals fed normal protein diets and protein-restricted diets. PMID:12204828

  17. Metabolic and Genomic Response to Dietary Isocaloric Protein Restriction in the Rat*

    PubMed Central

    Kalhan, Satish C.; Uppal, Sonal O.; Moorman, Jillian L.; Bennett, Carole; Gruca, Lourdes L.; Parimi, Prabhu S.; Dasarathy, Srinivasan; Serre, David; Hanson, Richard W.

    2011-01-01

    We have examined hepatic, genomic, and metabolic responses to dietary protein restriction in the non-pregnant Sprague-Dawley rat. Animals were pair-fed either a 6 or 24% casein-based diet for 710 days. At the end of the dietary period, a microarray analysis of the liver was performed, followed by validation of the genes of interest. The rates of appearance of phenylalanine, methionine, serine, and glucose and the contribution of pyruvate to serine and glucose were quantified using tracer methods. Plasma and tissue amino acid levels, enzyme activities, and metabolic intermediates were measured. Protein restriction resulted in significant differential expression of a number of genes involved in cell cycle, cell differentiation, transport, transcription, and metabolic processes. RT-PCR showed that the expression of genes involved in serine biosynthesis and fatty acid oxidation was higher, and those involved in fatty acid synthesis and urea synthesis were lower in the liver of protein-restricted animals. Free serine and glycine levels were higher and taurine levels lower in all tissues examined. Tracer isotope studies showed an ?50% increase in serine de novo synthesis. Pyruvate was the primary (?90%) source of serine in both groups. Transmethylation of methionine was significantly higher in the protein-restricted group. This was associated with a higher S-adenosylmethionine/S-adenosylhomocysteine ratio and lower cystathione ?-synthase and cystathionine ?-lyase activity. Dietary isocaloric protein restriction results in profound changes in hepatic one-carbon metabolism within a short period. These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine. PMID:21147771

  18. Time window-dependent effect of perinatal maternal protein restriction on insulin sensitivity and energy substrate oxidation in adult male offspring.

    PubMed

    Agnoux, Aurore Martin; Antignac, Jean-Philippe; Simard, Gilles; Poupeau, Guillaume; Darmaun, Dominique; Parnet, Patricia; Alexandre-Gouabau, Marie-Ccile

    2014-07-15

    Epidemiological and experimental evidence suggests that a suboptimal environment during perinatal life programs offspring susceptibility to the development of metabolic syndrome and Type 2 diabetes. We hypothesized that the lasting impact of perinatal protein deprivation on mitochondrial fuel oxidation and insulin sensitivity would depend on the time window of exposure. To improve our understanding of underlying mechanisms, an integrative approach was used, combining the assessment of insulin sensitivity and untargeted mass spectrometry-based metabolomics in the offspring. A hyperinsulinemic-euglycemic clamp was performed in adult male rats born from dams fed a low-protein diet during gestation and/or lactation, and subsequently exposed to a Western diet (WD) for 10 wk. Metabolomics was combined with targeted acylcarnitine profiling and analysis of liver gene expression to identify markers of adaptation to WD that influence the phenotype outcome evaluated by body composition analysis. At adulthood, offspring of protein-restricted dams had impaired insulin secretion when fed a standard diet. Moreover, rats who demonstrated catch-up growth at weaning displayed higher gluconeogenesis and branched-chain amino acid catabolism, and lower fatty acid ?-oxidation compared with control rats. Postweaning exposure of intrauterine growth restriction-born rats to a WD exacerbated incomplete fatty acid ?-oxidation and excess fat deposition. Control offspring nursed by protein-restricted mothers showed peculiar low-fat accretion through adulthood and preserved insulin sensitivity even after WD-exposure. Altogether, our findings suggest a testable hypothesis about how maternal diet might influence metabolic outcomes (insulin sensitivity) in the next generation such as mitochondrial overload and/or substrate oxidation inflexibility dependent on the time window of perinatal dietary manipulation. PMID:24808498

  19. Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny

    PubMed Central

    Guzmn, C; Cabrera, R; Crdenas, M; Larrea, F; Nathanielsz, P W; Zambrano, E

    2006-01-01

    Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function. PMID:16497715

  20. Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny.

    PubMed

    Guzmn, C; Cabrera, R; Crdenas, M; Larrea, F; Nathanielsz, P W; Zambrano, E

    2006-04-01

    Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function. PMID:16497715

  1. Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

    SciTech Connect

    Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

    1988-01-01

    The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted).

  2. Enhanced Mesenteric Arterial Responsiveness to Angiotensin II Is Androgen Receptor-Dependent in Prenatally Protein-Restricted Adult Female Rat Offspring1

    PubMed Central

    Sathishkumar, Kunju; Balakrishnan, Meena P.; Yallampalli, Chandrasekhar

    2014-01-01

    ABSTRACT Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent. PMID:25550341

  3. Protein restriction during gestation alters histone modifications at the glucose transporter 4 (GLUT4) promoter region and induces GLUT4 expression in skeletal muscle of female rat offspring.

    PubMed

    Zheng, Shasha; Rollet, Michelle; Pan, Yuan-Xiang

    2012-09-01

    Maternal nutrition during pregnancy is an intrauterine factor that results in alteration of the offspring genome and associates with disease risk in the offspring. We investigated the impact of a maternal low-protein (LP) diet on the expression of glucose transporter 4 (GLUT4) in offspring skeletal muscle. GLUT4 is an insulin-regulated glucose transporter involved in insulin sensitivity and carbohydrate metabolism in muscle cells. We observed sex-dependent GLUT4 mRNA expression and increased GLUT4 protein content in female pup skeletal muscle with maternal LP. Analysis of transcriptional and epigenetic regulation of increased skeletal muscle GLUT4 expression in offspring rats revealed the regulatory mechanisms involved. The protein level of myocyte enhancer factor 2A (MEF2A), which has been known as an activator of GLUT4 transcription via the ability to carry out specific binding to the GLUT4 MEF2 binding sequence, increased in female pups whose mothers were fed a LP diet. Modifications of chromatin structure, including acetylated histone H3, acetylated histone H4 and di-methylated histone H3 at lysine 4, were detected at a significantly increased level at the GLUT4 promoter region in female pup muscle following a maternal LP diet. Glycogen content was also detected as up-regulated, accompanied by increased glycogen synthase in LP female offspring muscle. These results document that maternal protein restriction during pregnancy induces GLUT4 expression in female offspring skeletal muscle but not in males, which may indicate sex-dependent adaptation of glucose metabolism to a maternal LP diet. PMID:22079207

  4. Taurine Supplementation Reduces Blood Pressure and Prevents Endothelial Dysfunction and Oxidative Stress in Post-Weaning Protein-Restricted Rats

    PubMed Central

    Maia, Aline R.; Batista, Thiago M.; Victorio, Jamaira A.; Clerici, Stefano P.; Delbin, Maria A.; Carneiro, Everardo M.; Davel, Ana P.

    2014-01-01

    Introduction Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats. Methods and Results Weaned male Wistar rats were fed normal- (12%, NP) or low-protein (6%, LP) diets for 90 days. Half of the NP and LP rats concomitantly received 2.5% taurine supplementation in the drinking water (NPT and LPT, respectively). LP rats showed elevated systolic, diastolic and mean arterial blood pressure versus NP rats; taurine supplementation partially prevented this increase. There was a reduced relaxation response to acetylcholine in isolated thoracic aortic rings from the LP group that was reversed by superoxide dismutase (SOD) or apocynin incubation. Protein expression of p47phox NADPH oxidase subunit was enhanced, whereas extracellular (EC)-SOD and endothelial nitric oxide synthase phosphorylation at Ser 1177 (p-eNOS) were reduced in aortas from LP rats. Furthermore, ROS production was enhanced while acetylcholine-induced NO release was reduced in aortas from the LP group. Taurine supplementation improved the relaxation response to acetylcholine and eNOS-derived NO production, increased EC-SOD and p-eNOS protein expression, as well as reduced ROS generation and p47phox expression in the aortas from LPT rats. LP rats showed an increased aortic wall/lumen ratio and taurine prevented this remodeling through a reduction in wall media thickness. Conclusion Our data indicate a protective role of taurine supplementation on the high blood pressure, endothelial dysfunction and vascular remodeling induced by post-weaning protein restriction. The beneficial vascular effect of taurine was associated with restoration of vascular redox homeostasis and improvement of NO bioavailability. PMID:25170895

  5. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    PubMed Central

    Nayak, Prasunpriya; Chatterjee, Ajay K

    2003-01-01

    Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

  6. Pre- and/or postnatal protein restriction in rats impairs learning and motivation in male offspring.

    PubMed

    Reyes-Castro, L A; Rodriguez, J S; Rodrguez-Gonzlez, G L; Wimmer, R D; McDonald, T J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2011-04-01

    Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.40.8 and 3.80.3 sessions, respectively, p<0.05). Performance in fixed ratio-5 conditioning showed the RR (5.41.1), CR (4.00.8), and RC (5.00.8) offspring required more sessions to reach performance criterion than CC offspring (2.50.5, p<0.05). Furthermore, motivational effects during the progressive ratio test revealed less responding in the RR (48.117), CR (74.78.4), and RC (65.911.2) for positive reinforcement vs. the CC offspring (131.57.5, p<0.05). These findings demonstrate negative developmental programming effects due to perinatal isocaloric low protein diet on learning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior. PMID:21078378

  7. Postnatal prebiotic fiber intake in offspring exposed to gestational protein restriction has sex-specific effects on insulin resistance and intestinal permeability in rats.

    PubMed

    Hallam, Megan C; Reimer, Raylene A

    2014-10-01

    Maternal protein restriction (PR) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. A few studies have shown that this adverse programming can be reversed by dietary or hormonal therapies early in postnatal life. The objective of this study was to determine if a weaning diet high in prebiotic fiber could mitigate some of the negative effects of maternal PR, such as increased adiposity and impaired glucose tolerance. Wistar rats were fed a low- (8%) or normal- (20%) protein diet during pregnancy. Male and female pups were weaned onto control (C; 5% fiber, 20% protein) or high (prebiotic) fiber (HF; 21% wt:wt, 1:1 ratio oligofructose and inulin at 4-10 wk; 10% wt:wt, 1:1 ratio oligofructose and inulin at 10-24 wk; 17.3% protein) diets. At 24 wk of age, glucose tolerance, body composition, satiety hormones, gut microbiota, and markers of intestinal permeability were measured in the offspring. Maternal PR reduced offspring birth weight by 5% and lean mass by 9% compared with the C offspring (P < 0.007). HF-fed offspring had lower body weights and percentage body fat (∼23% in males, ∼19% in females) at 24 wk than did C offspring (P < 0.02). Compared with C pups, pups fed the HF diet had greater cecal Bifidobacterium spp. (>5-fold) and plasma concentrations of the gut trophic hormone glucagon-like peptide 2 (GLP-2) (P < 0.05). In male PR offspring fed the HF diet, insulin resistance measured by the homeostasis model assessment of insulin resistance was reduced by 81% compared with those fed the C diet (P = 0.02). In female PR offspring fed the HF diet, plasma endotoxin was greater and colonic tight junction protein 1 (Tjp1) expression was lower than in those fed the C diet. A high prebiotic fiber weaning diet mitigated increased adiposity and insulin resistance associated with maternal PR, which could improve health and decrease risk of chronic disease in offspring born to malnourished dams. However, the functional importance of sex-specific changes in markers of intestinal barrier function warrants further investigation. PMID:25080539

  8. Maternal protein restriction induces early-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring

    PubMed Central

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin

    2015-01-01

    Aims/Introduction Maternal undernutrition during pregnancy and/or lactation can alter the offspring's response to environmental challenges, and thus increases the risk of the development of metabolic diseases at a later age. However, whether maternal protein restriction can modulate glucose metabolism in the early life of offspring is less understood. Furthermore, we explored the potential underlying mechanisms that illustrate this phenotype. Materials and Methods To test this hypothesis, we examined the offspring of C57BL/6J mice at weaning to determine the effects of feeding their mothers a low-protein diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time polymerase chain reaction were utilized to explore the altered hepatic genes expression. Results The offspring of dams fed a low-protein diet had a lower birthweight and bodyweight, impaired glucose tolerance, decreased insulin sensitivity, and decreased serum cholesterol at weaning. Using gene array experiments, 253 differentially expressed genes were identified in the liver tissues of the offspring between the two groups. Bioinformatic analyses showed that all differentially expressed genes were mapped to 11 pathways. We focused on the ‘peroxisome proliferator-activated receptor signaling pathway,’ because peroxisome proliferator-activated receptors have emerged as central regulators of glucose and lipid homeostasis. Quantitative real-time polymerase chain reaction was utilized for the validation of genes in the pathway. Conclusions A maternal low-protein diet during pregnancy and lactation promotes early-onset glucose intolerance in the offspring mice, and the altered hepatic genes expression in peroxisome proliferator-activated receptor signaling pathway could play role in regulating this phenomenon. PMID:25969711

  9. Maternal metabolizable protein restriction during late gestation on uterine and umbilical blood flows and maternal and fetal amino acid concentrations near term in sheep.

    PubMed

    Lekatz, L A; Swanson, T J; Camacho, L E; Van Emon, M L; Schauer, C S; Maddock Carlin, K R; Hammer, C J; Lemley, C O; Vonnahme, K A

    2015-07-01

    To examine the effects of maternal metabolizable protein (MP) restriction during late gestation on uterine and umbilical blood flows, conceptus size, and amino acid concentrations in the uterine and umbilical vessels, 11 ewes with singleton pregnancies were assigned to one of three isocaloric diets formulated to provide 60% of MP (MP60), 80% of MP (MP80), or 100% of MP (MP100) requirements from days 100 to 130 of gestation. On day 130 of gestation, intraoperative uterine and umbilical blood flows were obtained as well as serum samples from the uterine artery, uterine vein, umbilical artery, and umbilical vein. Ewes on the MP60 diet had lighter (P=0.04) and smaller (P≤0.05) fetuses, but increased (P=0.02) uterine blood flow relative to fetal weight compared with MP100 ewes, with MP80 being intermediate. Umbilical blood flow was similar (P=0.70) across treatments. Glutamine, glycine, isoleucine, leucine, ornithine, serine, and valine concentrations were impacted (P≤0.02) by maternal treatment. While uterine flux of total serum nitrites was greater (P=0.03) in MP60 and MP80 ewes compared with MP100 ewes, fetal flux did not differ. Decreased maternal protein intake resulted in less (P<0.01) maternal cytochrome P450 1A enzyme activity. There were minimal impacts of maternal diet on steroid concentrations. Maternal dietary protein may alter fetal growth by impacting placental vasculature function and nutrient absorptive capabilities. PMID:26024963

  10. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  11. Impaired β-cell function in the adult offspring of rats fed a protein-restricted diet during lactation is associated with changes in muscarinic acetylcholine receptor subtypes.

    PubMed

    Oliveira, Júlio C de; Miranda, Rosiane A; Barella, Luiz F; Torrezan, Rosana; Agostinho, Aryane R; Ribeiro, Tatiane A S; Franco, Claudinéia C S; Malta, Ananda; Tófolo, Laize P; Gravena, Clarice; Mathias, Paulo C F

    2014-01-28

    Impaired pancreatic β-cell function, as observed in the cases of early nutrition disturbance, is a major hallmark of metabolic diseases arising in adulthood. In the present study, we aimed to investigate the function/composition of the muscarinic acetylcholine receptor (mAChR) subtypes, M2 and M3, in the pancreatic islets of adult offspring of rats that were protein malnourished during lactation. Neonates were nursed by mothers that were fed either a low-protein (4 %, LP) or a normal-protein (23 %, NP) diet. Adult rats were pre-treated with anti-muscarinic drugs and subjected to the glucose tolerance test; the function and protein expression levels of M2mAChR and M3mAChR were determined. The LP rats were lean and hypoinsulinaemic. The selective M2mAChR antagonist methoctramine increased insulinaemia by 31 % in the NP rats and 155 % in the LP rats, and insulin secretion was increased by 32 % in the islets of the NP rats and 88 % in those of the LP rats. The selective M3mAChR antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide decreased insulinaemia by 63 % in the NP rats and 40 % in the LP rats and reduced insulin release by 41 % in the islets of the NP rats and 28 % in those of the LP rats. The protein expression levels of M2mAChR and M3mAChR were 57 % higher and 53 % lower, respectively, in the islets of the LP rats than in those of the NP rats. The expression and functional compositions of M2mAChR and M3mAChR were altered in the islets of the LP rats, as a result of metabolic programming caused by the protein-restricted diet, which might be another possible effect involved in the weak insulin secretion ability of the islets of the programmed adult rats. PMID:23841989

  12. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development.

    PubMed

    Zambrano, E; Rodrguez-Gonzlez, G L; Guzmn, C; Garca-Becerra, R; Boeck, L; Daz, L; Menjivar, M; Larrea, F; Nathanielsz, P W

    2005-02-15

    Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. PMID:15611025

  13. Compensatory mammary growth following protein restriction during pregnancy and lactation increases early-onset mammary tumor incidence in rats.

    PubMed

    Fernandez-Twinn, D S; Ekizoglou, S; Gusterson, B A; Luan, Jian'an; Ozanne, S E

    2007-03-01

    Breast cancer incidence is increased in women with both high and low birth weight. The latter is also associated with hyperglycaemia, insulin resistance and type-2 diabetes, each of which independently increases breast cancer risk. We showed previously in our model of poor early-growth that pregnancy estradiol levels were raised while offspring developed type-2 diabetes. We hypothesized that nutritionally-induced poor early-growth influences breast cancer risk and investigated this in our model. Wistar rat dams were given either a control diet (20% casein) or an isocaloric low-protein (LP) diet (8% casein) throughout pregnancy and lactation. Offspring postnatal mammary gland development was assessed by morphometry. To identify potential growth mechanisms, we measured protein expression of receptors involved in insulin and hormone signaling, both in cleared mammary gland lysates and isolated epithelial cells. Mammary tumor incidence and latency (n=96) was monitored after three weekly intraperitoneal nitrosomethylurea injections (50 mg/kg body wt). LP offspring displayed reduced postnatal ductal branching and epithelial invasion at 3 weeks, followed by compensatory mammary growth 1 week later coinciding with increased protein expression of receptors to insulin, IGF-1 and estrogen. Significantly, early-mammary tumor incidence (0-16 weeks post-treatment) was doubled in LP offspring [RR, 2.13 (1.02, 4.45); P=0.046]. The data suggest that poor early nutrition has an important influence on the mammary primordium, and increases future susceptibility to breast cancer. Up-regulated growth factor and hormone signaling during compensatory mammary growth may mediate this increased susceptibility and present potential targets for intervention. PMID:16952910

  14. Maternal diet influences DNA damage, aortic telomere length, oxidative stress, and antioxidant defense capacity in rats.

    PubMed

    Tarry-Adkins, J L; Martin-Gronert, M S; Chen, J-H; Cripps, R L; Ozanne, S E

    2008-06-01

    Low birth weight is associated with increased cardiovascular disease (CVD) in humans. Detrimental effects of low birth weight are amplified by rapid catch-up growth. Conversely, slow growth during lactation reduces CVD risk. Gestational protein restriction causes low birth weight, vascular dysfunction, and accelerated aging in rats. Atherosclerotic aortic tissue has shortened telomeres, and oxidative stress accelerates telomere shortening through generation of DNA single-strand breaks (ssbs). This study tested the hypothesis that maternal diet influences aortic telomere length through changes in DNA ssbs, antioxidant capacity, and oxidative stress. We used our models of gestational protein restriction followed by rapid catch-up growth (the recuperated group) and protein restriction during lactation (the postnatal low-protein [PLP] group). Southern blotting revealed fewer aortic DNA ssbs and subsequently fewer short telomeres (P<0.05) in the PLP group. This result was associated with reduced (P<0.01) 8-hydroxy-2-deoxyguanosine, a marker of oxidative stress. PLP animals expressed increased (P<0.01) manganese superoxide-dismutase, copper-zinc superoxide-dismutase, catalase, and glutathione-reductase. Age-dependent changes in antioxidant defense enzymes indicated more protection to oxidative stress in the PLP animals; conversely, recuperated animals demonstrated age-associated impairment of antioxidant defenses. We conclude that maternal diet has a major influence on aortic telomere length. This finding may provide a mechanistic link between early growth patterns and CVD. PMID:18230683

  15. Antipsychotic drugs on maternal behavior in rats.

    PubMed

    Li, Ming

    2015-09-01

    Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and the atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and amisulpride, disrupt active maternal responses (e.g. pup retrieval, pup licking, and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at clinically relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, whereas 5-HT2A/2C receptors contributing more to atypical drug-induced disruptions. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps understand the extent and mechanisms of impact of antipsychotic medications on human maternal care, but is also important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic effects and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects. PMID:26221833

  16. Early changes of hypothalamic angiotensin II receptors expression in gestational protein-restricted offspring: effect on water intake, blood pressure and renal sodium handling.

    PubMed

    de Lima, Marcelo Cardoso; Scabora, José Eduardo; Lopes, Agnes; Mesquita, Flávia Fernandes; Torres, Daniele; Boer, Patrícia Aline; Gontijo, José Antonio Rocha

    2013-09-01

    The current study examines changes in the postnatal hypothalamic angiotensin receptors by maternal protein restriction (LP), and its impact on in uteri programming of hypertension in adult life. The data show that LP male pup body weight was significantly reduced when compared to that of control (NP) pups. Also, immunoblotting analysis demonstrated a significantly decreased expression of type 1 AngII receptors (AT1R) in the entire hypothalamic tissue extract of LP rats at 12 days of age compared to age-matched NP offspring. Conversely, the expression of the type 2 AngII (AT2R) receptors in 12-day- and 16-week-old LP hypothalamus was significantly increased. The current data show the influence of central AngII administration on water consumption in a concentration-dependent fashion, but also demonstrate that the water intake response to AngII was strikingly attenuated in 16-week-old LP. These results may be related to decreased brain arginine vasopressin (AVP) expression appearing in maternal protein-restricted offspring. The present investigation shows an early decrease in fractional urinary sodium excretion in maternal protein-restricted offspring. The decreased fractional sodium excretion was accompanied by a fall in proximal sodium excretion and occurred despite unchanged creatinine clearance. These effects were associated with a significant enhancement in arterial blood pressure in the LP group, but the precise mechanism of these phenomena remains unknown. PMID:22936038

  17. MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT

    EPA Science Inventory

    MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT.
    C. Lau and J.M. Rogers, Reproductive Toxicology Division, NHEERL, ORD, USEPA, Research Triangle Park, NC, USA

    Perfluorooctane sulfonate (PFOS), an environmentally persistent compound used ...

  18. Central V1b receptor antagonism in lactating rats: impairment of maternal care but not of maternal aggression.

    PubMed

    Bayerl, D S; Klampfl, S M; Bosch, O J

    2014-12-01

    Maternal behaviour in rodents is mediated by the central oxytocin and vasopressin systems, amongst others. The role of vasopressin, acting via the V1a receptor (V1aR), on maternal careand maternal aggression has recently been described. However, a potential involvement of the V1b receptor (V1bR) in maternal behaviour has only been demonstrated in knockout mice. The present study aimed to examine the effects of central pharmacological manipulation of the V1bR on maternal behaviour in lactating Wistar rats. On pregnancy day 18, female rats were implanted with a guide cannula targeting the lateral ventricle. After parturition, dams received an acute central infusion of a specific V1bR agonist (d[Leu4,Lys8]VP) or V1bR antagonist (SSR149415) once daily, followed by observations of maternal care [lactation day (LD) 1], maternal motivation in the pup retrieval test (LD 2), anxiety-related behaviour on the elevated plus-maze (LD 3) and maternal aggression in the maternal defence test followed by maternal care monitoring (LD 4). Our data demonstrate that, under nonstress conditions, the V1bR antagonist decreased the occurrence of both nursing and mother-pup interaction, whereas the V1bR agonist did not affect either parameter. Under stress conditions (i.e. after the maternal defence test), mother-pup interaction was decreased by infusion of the V1bR antagonist. During the maternal defence test, neither treatment affected aggressive or non-aggressive behaviour. Finally, neither treatment altered maternal motivation or anxiety. In conclusion, central V1bR antagonism modulates aspects of maternal care but not of maternal aggression or maternal motivation in lactating rats. These findings further extend our knowledge on the vasopressin system as a vital mediator of maternal behaviour. PMID:25283607

  19. Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat.

    PubMed

    Sherman, R C; Jackson, A A; Langley-Evans, S C

    1999-01-01

    Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension. PMID:10436308

  20. Supplementation of a maternal low-protein diet in rat pregnancy with folic acid ameliorates programming effects upon feeding behaviour in the absence of disturbances to the methionine-homocysteine cycle.

    PubMed

    Engeham, Sarah F; Haase, Andrea; Langley-Evans, Simon C

    2010-04-01

    Maternal protein restriction in rat pregnancy is associated with altered feeding behaviour in later life. When allowed to self-select their diet, rats subject to prenatal undernutrition show an increased preference for fatty foods. The main aim of the present study was to evaluate the contribution of folic acid in the maternal diet to programming of appetite, since disturbances of the folate and methionine-homocysteine cycles have been suggested to impact upon epigenetic regulation of gene expression and hence programme long-term physiology and metabolism. Pregnant rats were fed diets containing either 9 or 18 % casein by weight, with folate provided at either 1 or 5 mg/kg diet. Adult male animals exposed to low protein (LP) in fetal life exhibited increased preference for high-fat food. Providing the higher level of folate in the maternal diet prevented this effect of LP, but offspring of rats fed 18 % casein diet with additional folate behaved in a similar manner to LP-exposed animals. Among day 20 gestation fetuses, it was apparent that both protein restriction and maternal folate supplementation could have adverse effects upon placental growth. Examination of methionine-homocysteine and folate cycle intermediates, tissue glutathione concentrations and expression of mRNA for methionine synthase, DNA methyltransferase 1 and methyltetrahydrofolate reductase revealed no gross disturbances of folate and one-carbon metabolism in either maternal or fetal tissue. The present findings indicated that any role for DNA methylation in programming of physiology is not related to major perturbations of folate metabolism, and is likely to be gene-specific rather than genome-wide. PMID:19941678

  1. Immune responsiveness of Japanese quail selected for egg yolk testosterone content under severe protein restriction.

    PubMed

    Kankova, Zuzana; Okuliarova, Monika; Zeman, Michal

    2014-11-01

    Yolk testosterone concentrations vary in response to environmental conditions and different testosterone contents can subsequently modify the phenotypic traits of offspring. Apart from effects on growth, proactive behaviour and secondary sexual characteristics, the possible negative impacts of maternal testosterone on the immune system are often considered a limitation for its deposition. The effects of maternal testosterone can be modulated by postnatal environmental conditions, such as the availability of food resources. However, the majority of studies considering the effects of maternal testosterone on the immune system have been conducted under optimum conditions. We evaluated the influence of genetic selection for high (HET) and low (LET) egg testosterone content in Japanese quail on immune responsiveness of offspring to phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) stimulation under severe protein restriction. Protein restriction negatively influenced body weight and performance in the PHA-test. We observed an increase in Cort (corticosterone) and He/Ly (heterophil/lymphocyte ratio) after LPS, while no changes occurred in total IgY levels in the protein-restricted group. HET quails showed higher body mass and total IgY levels and lower He/Ly ratio than LET quails, while the PHA index and Cort concentration did not differ between lines. No interactions were found between protein restriction and genetic line. In conclusion, the immune response was not compromised under conditions of severe protein restriction in the faster growing HET line compared with the LET line. We hypothesise that the immune responsiveness of birds with higher yolk testosterone may be linked with other maternally-derived substances in a context-dependent manner. PMID:25086332

  2. Maternal immune activation increases seizure susceptibility in juvenile rat offspring.

    PubMed

    Yin, Ping; Zhang, Xin-Ting; Li, Jun; Yu, Lin; Wang, Ji-Wen; Lei, Ge-Fei; Sun, Ruo-Peng; Li, Bao-Min

    2015-06-01

    Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia. PMID:25982885

  3. Can early protein restriction induce the development of binge eating?

    PubMed

    Fechine, Madge Farias; Borba, Tássia Karin; Cabral-Filho, José Eulálio; Bolaños-Jiménez, Francisco; Lopes-de-Souza, Sandra; Manhães-de-Castro, Raul

    2016-04-01

    We tested the hypothesis that perinatal undernourishment is a factor for binge eating. At 52 days rats born from dams fed on 17% protein (Control) or 8% protein (Undernourished) were distributed into four groups, two of which continued to be fed ad libitum chow and two were submitted to three consecutive Restricted/Refeeding (R/R) cycles. According to the following schedule: Control Naïve (from mothers fed 17% protein/no restriction phase); Control Restricted (from mothers fed 17% protein/restriction phase); Undernourished Naïve (from mothers fed 8% protein/no restriction phase); and Undernourished Restricted (from mothers fed 8% protein/restriction phase). Each cycle consisted of a restriction phase (in the first four days 40% of the mean daily individual chow intake was offered for consumption), followed by a refeeding phase (4 days of chow ad libitum). After the three cycles, all animals were subjected to a feeding test (chow diet and palatable food ad libitum for 24h). During the feeding test, the Undernourished Restricted demonstrated rebound hyperphagia during 2, 4 and 6h. These results suggest the perinatal undernourishment cannot contribute to a binge eating phenotype. PMID:26836391

  4. Metyrapone Alleviates Deleterious Effects of Maternal Food Restriction on Lung Development and Growth of Rat Offspring

    PubMed Central

    Paek, David S.; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S.

    2015-01-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. PMID:24916330

  5. Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

    PubMed

    Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K

    2015-02-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor ?, increase in myogenic proteins (fibronectin, ?-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and ?-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. PMID:24916330

  6. Lactating Rats Retain Nursing Behavior and Maternal Care in Space

    NASA Technical Reports Server (NTRS)

    Daly, Megan E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    In 1997, suckling mammals were flown in space for the first time as part of the NIH.R3 experiment sponsored jointly by NIH (National Institutes of Health) and NASA. Six rat dams and litters (Rattus norvegicus) were launched on an eight-day Space Shuttle mission at each of three postnatal ages (P5, P8, and P15). Dams and litters (N = 10 pups/litter) were housed within modified Animal Enclosure Modules (AEMs). Comparisons were made to ground controls. Dams and litters were videotaped daily in flight. The P8 and P15 flight litters showed excellent survival (99%) and weight gain relative to AEM ground controls, whereas P5 litters showed reduced survival (0% and 60%, respectively) and weight gain (less than 40% AEM). To examine the possibility that failures of maternal care contributed to P5 results, we analyzed the dams' in-flight nursing, licking and retrieving from four video segments ranging from twelve to fifteen minutes in length with control data derived from multiple ground segments. Video analyses revealed clear evidence of maternal care in flight. For P5 dams, frequency and duration of nursing and licking bouts fell within or above one standard deviation of control values. Retrieving was noted in the P5 and P8 groups only. The observed results suggest that factors other than maternal care contributed to the low survival rates and body weight gains of the P5 flight offspring.

  7. Long maternal separation has protective effects in rats exposed to activity-based anorexia.

    PubMed

    Carrera, O; Cerrato, M; Sanchez, A; Gutierrez, E

    2009-12-01

    This study examined the effect of three neonatal treatments of maternal separation during infancy in young adult rats exposed to standard activity-based anorexia (ABA) consisting of food restriction plus free access to an activity wheel. During the first 20 postnatal days of life rat pups were exposed to periods of either brief maternal separation (BMS, 15 min), long maternal separation (LMS, 180 min), or were non-handled (NH). Thereafter, male and female rats were exposed to ABA. Neonatal treatment produced no significant differences in the survival time of male rats, whereas survival was greater in female rats exposed to LMS than in NH rats under ABA procedure. In conclusion, prolonged maternal separation appears to promote resistance in female animals subjected to harsh ABA life-threatening conditions. PMID:19728326

  8. Protein Content and Methyl Donors in Maternal Diet Interact to Influence the Proliferation Rate and Cell Fate of Neural Stem Cells in Rat Hippocampus

    PubMed Central

    Amarger, Valrie; Lecouillard, Angle; Ancellet, Laure; Grit, Isabelle; Castellano, Blandine; Hulin, Philippe; Parnet, Patricia

    2014-01-01

    Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation. PMID:25317634

  9. IFITM Proteins Restrict Viral Membrane Hemifusion

    PubMed Central

    Golfetto, Ottavia; Bungart, Brittani; Li, Minghua; Ding, Shilei; He, Yuxian; Liang, Chen; Lee, James C.; Gratton, Enrico; Cohen, Fredric S.; Liu, Shan-Lu

    2013-01-01

    The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection. PMID:23358889

  10. Effect of dietary protein restriction on renal ammonia metabolism.

    PubMed

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Guo, Hui; Verlander, Jill W; Weiner, I David

    2015-06-15

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

  11. Arginine Vasopressin V1a Receptor Antagonist Impairs Maternal Memory in Rats

    PubMed Central

    Nephew, Benjamin C.; Bridges, Robert S.

    2008-01-01

    Primiparous female rats rapidly respond to foster pups following an extended separation from pups after an initial maternal experience. This consolidation of maternal behavior has been referred to as maternal memory. The neurochemical regulation of maternal memory is not clearly understood. One neuropeptide that may mediate maternal memory is arginine vasopressin (AVP), a neuropeptide which is modulated around the time of parturition and has an established role in learning and memory processes. Thus, the present studies examine the possible involvement of AVP in the establishment of maternal memory in female rats. Pregnant rats were implanted with chronic cannulae connected to subcutaneous osmotic minipumps filled with a V1a receptor antagonist [d(CH2)5Tyr(Me)AVP, 0.1–12.5 ng/hr] or saline vehicle which were chronically infused either into the lateral ventricles or bilaterally into the medial amygdala beginning on day 18 of gestation. Both the osmotic pumps and the newborn pups were removed 24 hours following parturition. The effects of the V1a antagonist treatments on social recognition and maternal behavior were measured following parturition and maternal memory was assessed following a ten day separation from pups. Whereas none of the AVP treatments affected the initial establishment of maternal behavior postpartum, maternal memory was impaired in rats infused into the amygdala with the AVP antagonist (1.25 and 12.5 ng/hr). Social recognition was not impaired by intracerebroventricular infusion of either the 0.1 or 1.0 ng/hr dose of the V1a antagonist. The present results suggest a role for medial amygdaloid V1a receptors in the establishment of maternal memory. PMID:18620713

  12. Maternal-infant separation impedes changes in feeding behavior during estrous cycle of rats

    PubMed Central

    Iwasaki, Shinichi; Inoue, Koki

    2015-01-01

    Traumatic and stressful events during childhood are associated with the development of eating disorders. We conducted an animal study to test if association stress in childhood affects ingestive behavior later in life by using female rats that have an adjusted estrous cycle. First, electrical impedance of the vagina was conducted to test estrous cycle adjustment. Second, the effects of 6 h per day maternal separation from birth to weaning, which models a psychologically stressful experience in childhood, was used to test feeding behavior during an ovarian cycle in female adult rats with matched estrous cycles. Food and water intake in maternal separated and non-separated rats was measured in each estrous phase. Non-separated rats showed periodical changes, but maternal separated rats showed no significant changes in food and water intake during an estrous cycle. An opposing tendency for food and water intake was seen between maternal separated and non-separated rats. These observations suggest that electrical impedance of the vagina showed the highest value in the estrous phase of rats housed in a reversed light-dark cycle, and maternal separation was found to disturb changes in feeding behavior during the estrous cycle. PMID:26119792

  13. Developmental triclosan exposure decreases maternal and neonatal thyroxine in rats.

    PubMed

    Paul, Katie B; Hedge, Joan M; Devito, Michael J; Crofton, Kevin M

    2010-12-01

    Disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. The present study tested the hypothesis that perinatal triclosan exposure of dams decreases thyroxine in dams and offspring prior to weaning. Pregnant Long-Evans rats received triclosan by oral gavage (0-300 mg/kg/d) in corn oil from gestational day (GD)6 through postnatal day (PND)21. Serum was obtained from pups on PND4, 14, and 21, and from dams on PND22. Serum thyroxine (T4) was reduced 31% in dams on PND22. In pups, a unique pattern of hypothyroxinemia was observed; serum T4 decreased 27% in PND4 pups with no significant reduction observed on PND14 or PND21. Comparable reductions of approximately 30% in serum T4 at 300 mg/kg/d for dams and PND4 neonates and a lack of effect at PND14 and PND21 suggest that toxicokinetic or toxicodynamic factors may have contributed to a reduced exposure or a reduced toxicological response during the lactation period. PMID:20954233

  14. Effects of maternal separation on the dietary preference and behavioral satiety sequence in rats.

    PubMed

    da Silva, M C; de Souza, J A; Dos Santos, L O; Pinheiro, I L; Borba, T K F; da Silva, A A M; de Castro, R M; de Souza, S L

    2014-06-01

    This study investigated the effects of maternal separation on the feeding behavior of rats. A maternal separation model was used on postnatal day 1 (PND1), forming the following groups: in the maternal separation (MS) group, pups were separated from their mothers each day from PND1 to PND14, whereas in the control (C) group pups were kept with their mothers. Subgroups were formed to study the effects of light and darkness: control with dark and light exposure, female and male (CF and CM), and maternal separation with dark and light exposure, female and male (SDF, SDM, SLF and SLM). Female rats had higher caloric intake relative to body weight compared with male controls in the dark period only (CF=23.30.5 v. CM=18.20.7, P<0.001). Macronutrient feeding preferences were observed, with male rats exhibiting higher caloric intake from a protein diet as compared with female rats (CF=4.10.7, n=8 v. CM=7.00.5, n=8, P<0.05) and satiety development was not interrupted. Female rats had a higher adrenal weight as compared with male rats independently of experimental groups and exhibited a higher concentration of serum triglycerides (n=8, P<0.001). The study indicates possible phenotypic adjustments in the structure of feeding behavior promoted by maternal separation, especially in the dark cycle. The dissociation between the mother's presence and milk intake probably induces adjustments in feeding behavior during adulthood. PMID:24901662

  15. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates

    PubMed Central

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  16. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates.

    PubMed

    Cutuli, Debora; Caporali, Paola; Gelfo, Francesca; Angelucci, Francesco; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Bisicchia, Elisa; Molinari, Marco; Farioli Vecchioli, Stefano; Petrosini, Laura

    2015-01-01

    Environmental enrichment (EE) is a widely used paradigm for investigating the influence of complex stimulations on brain and behavior. Here we examined whether pre-reproductive exposure to EE of female rats may influence their maternal care and offspring cognitive performances. To this aim, from weaning to breeding age enriched females (EF) were reared in enriched environments. Females reared in standard conditions were used as controls. At 2.5 months of age all females were mated and reared in standard conditions with their offspring. Maternal care behaviors and nesting activity were assessed in lactating dams. Their male pups were also behaviorally evaluated at different post-natal days (pnd). Brain BDNF, reelin and adult hippocampal neurogenesis levels were measured as biochemical correlates of neuroplasticity. EF showed more complex maternal care than controls due to their higher levels of licking, crouching and nest building activities. Moreover, their offspring showed higher discriminative (maternal odor preference T-maze, pnd 10) and spatial (Morris Water Maze, pnd 45; Open Field with objects, pnd 55) performances, with no differences in social abilities (Sociability test, pnd 35), in comparison to controls. BDNF levels were increased in EF frontal cortex at pups' weaning and in their offspring hippocampus at pnd 21 and 55. No differences in offspring reelin and adult hippocampal neurogenesis levels were found. In conclusion, our study indicates that pre-reproductive maternal enrichment positively influences female rats' maternal care and cognitive development of their offspring, demonstrating thus a transgenerational transmission of EE benefits linked to enhanced BDNF-induced neuroplasticity. PMID:25814946

  17. The effects of dopaminergic/serotonergic reuptake inhibition on maternal behavior, maternal aggression, and oxytocin in the rat.

    PubMed

    Johns, J M; Joyner, P W; McMurray, M S; Elliott, D L; Hofler, V E; Middleton, C L; Knupp, K; Greenhill, K W; Lomas, L M; Walker, C H

    2005-08-01

    Studies using dopaminergic and serotonergic agonists or antagonists implicate involvement of these systems in various aspects of early maternal behavior and postpartum aggression towards an intruder in rats, both of which are associated with the presence of oxytocin in specific brain regions. It is unclear however, if or how long-term uptake inhibition of either neurotransmitter system alone or in combination, affects oxytocin system dynamics or maternal behavior/aggression. Pregnant women frequently take drugs (antidepressants, cocaine) that induce long-term reuptake inhibition of dopamine and/or serotonin, thus it is important to understand these effects on behavior and biochemistry. Rat dams were treated throughout gestation with amfonelic acid, fluoxetine, or a combination of both, to investigate effects of reuptake inhibition of dopamine and serotonin systems respectively, on maternal behavior, aggression and oxytocin. The more appetitive aspects of maternal behavior (nesting, licking, touching) and activity were increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high dose combination more than other treatments. Aggression was decreased by amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition appears to have a strong effect on hippocampal oxytocin levels, while receptor dynamics may be more strongly affected by serotonin uptake inhibition. PMID:15996723

  18. Cocaine Disrupts Pup-Induced Maternal Behavior in Juvenile and Adult Rats

    PubMed Central

    Johns, Josephine M.; McMurray, Matthew S.; Hofler, Vivian E.; Jarrett, Thomas M.; Middleton, Christopher L.; Elliott, Deborah L.; Mirza, Raessa; Haslup, Amber; Elliott, Jay C.; Walker, Cheryl H.

    2007-01-01

    Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure. PMID:17698321

  19. Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats.

    PubMed

    Johns, Josephine M; McMurray, Matthew S; Hofler, Vivian E; Jarrett, Thomas M; Middleton, Christopher L; Elliott, Deborah L; Mirza, Raessa; Haslup, Amber; Elliott, Jay C; Walker, Cheryl H

    2007-01-01

    Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure. PMID:17698321

  20. The Effects of Bromocriptine Treatment During Early Pregnancy on Postpartum Maternal Behaviors in Rats

    PubMed Central

    Price, Anya K.; Bridges, Robert S.

    2016-01-01

    Prolactin, a hormone of the anterior pituitary, is involved in initiating maternal behavior, alleviating postpartum anxiety, and stimulating lactogenesis. Bromocriptine, a dopamine D2 receptor agonist, inhibits prolactin secretion. Bromocriptine administration represses postpartum maternal behaviors (pup retrieval) in mice, and causes elevated anxiety in the elevated plus maze [Larsen & Grattan (2010). Endocrinology 151(8): 38053814]. Whether similar effects exist in other species is unknown. The present study examined the possible involvement of prolactin during early gestation on maternal behavior and anxiety in rats. Bromocriptine given on days 24 of pregnancy resulted in impaired postpartum maternal behaviors in a novel environment during early lactation. However, compared to controls, bromocriptine-treated subjects did not exhibit increased postpartum anxiety in the elevated plus maze. These findings support work in mice that bromocriptine treatment during early gestation impedes postpartum maternal care, and indicate that early gestational hormonal status affects postpartum behavior more broadly in other mammals. PMID:24889499

  1. Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

    PubMed

    Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2015-11-01

    Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring. PMID:24753110

  2. Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction.

    PubMed

    Sano, Mitsue; Ferchaud-Roucher, Vronique; Kaeffer, Bertrand; Poupeau, Guillaume; Castellano, Blandine; Darmaun, Dominique

    2016-01-01

    L-Tryptophan (L-Trp) is a precursor for serotonin (5-HT) and nicotinamide adenine dinucleotide (NAD) synthesis. Both 5-HT and NAD may impact energy metabolism during gestation given that recent studies have demonstrated that increased 5-HT production is crucial for increasing maternal insulin secretion, and that sirtuin, an NAD(+)-dependent protein deacetylase, regulates endocrine signaling. Infants born with intrauterine growth restriction (IUGR) are at a higher risk of metabolic disease once they reach adulthood. IUGR is associated with altered maternal-fetal amino acid transfer. Whether IUGR affects L-Trp metabolism in mother and fetus has not been fully elucidated. Recently, we developed an analytical method using stable isotope-labeled L-Trp to explore the metabolism of L-Trp and its main metabolites, L-kynurenine (L-Kyn), 5-HT and quinolinic acid (QA). In this study, dams submitted to dietary protein restriction throughout gestation received intravenous infusions of stable isotope-labeled (15)N2-L-Trp to determine whether L-Trp metabolism is affected by IUGR. Samples were obtained from maternal, fetal and umbilical vein plasma, as well as the amniotic fluid (AF), placenta and liver of the mother and the fetus after isotope infusion. We observed evidence for active L-Trp transfer from mother to fetus, as well as de novo synthesis of 5-HT in the fetus. Plasma 5-HT was decreased in undernourished mothers. In IUGR fetuses, maternal-fetal L-Trp transfer remained unaffected, but conversion to QA was impaired, implying that NAD production also decreased. Whether such alterations in tryptophan metabolism during gestation have adverse consequences and contribute to the increased risk of metabolic disease in IUGR remains to be explored. PMID:26334345

  3. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    PubMed Central

    Wang, Qiong; Shao, Feng; Wang, Weiwen

    2015-01-01

    Early life adversity, such as postnatal maternal separation (MS), play a central role in the development of psychopathologies during individual ontogeny. In this study, we investigated the effects of repeated MS (4 h per day from postnatal day (PND) 121) on the brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc) and the hippocampus of male and female juvenile (PND 21), adolescent (PND 35) and young adult (PND 56) Wistar rats. The results indicated that MS increased BDNF in the CA1 and the dentate gyrus (DG) of adolescent rats as well as in the DG of young adult rats. However, the expression of BDNF in the mPFC in the young adult rats was decreased by MS. Additionally, in the hippocampus, there was decreased BDNF expression with age in both the MS and non separated rats. However, in the mPFC, the BDNF expression was increased with age in the non separated rats; nevertheless, the BDNF expression was significantly decreased in the MS young adult rats. In the NAc, the BDNF expression was increased with age in the male non-maternal separation (NMS) rats, and the young adult female MS rats had less BDNF expression than the adolescent female MS rats. The present study shows unique age-differently changes on a molecular level induced by MS and advances the use of MS as a valid animal model to detect the underlying neurobiological mechanisms of mental disorders. PMID:26388728

  4. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

    PubMed Central

    Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  5. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

    PubMed

    Paul, Heather A; Bomhof, Marc R; Vogel, Hans J; Reimer, Raylene A

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  6. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

    EPA Science Inventory

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  7. Intrauterine Growth Restricted Rats Exercised before and during Pregnancy: Maternal and Perinatal Repercussions

    PubMed Central

    Corvino, S. B.; Volpato, G. T.; Rudge, M. V. C.; Damasceno, D. C.

    2015-01-01

    This study aimed at evaluating the effect of swimming before and during pregnancy on rats born with intrauterine growth restriction (IUGR) and their offspring. For this, nondiabetic and streptozotocin-induced severely diabetic (SD) pregnant rats were mated and generated offspring with appropriate (control, C) and small (IUGR) for pregnancy age, respectively. Following that, C and IUGR groups were further distributed into nonexercised control (C), exercised control (Cex), nonexercised IUGR (IUGR), and exercised IUGR (IUGRex). IUGR rats presented lower mating rate than control rats. Regardless of physical exercise IUGR rats presented decreased body weight from birth to lactation. At 90 days of life, IUGR rats presented glucose intolerance. Maternal organ weights were increased and relative adiposity of IUGRex rats was lower than Cex. IUGR and IUGRex offspring presented reduced body weight than C and Cex, respectively. IUGRex dams presented an increased rate of appropriate for pregnancy age newborns. IUGEex male and female offspring relative brain weight was increased compared with Cex. Therefore, swimming before and during pregnancy prevented glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight in rats, showing the benefit of physical exercise for IUGR rats. PMID:26345406

  8. Toxic Effects of Maternal Zearalenone Exposure on Uterine Capacity and Fetal Development in Gestation Rats

    PubMed Central

    Zhang, Yuanyuan; Jia, Zhiqiang; Yin, Shutong; Gao, Rui; Qu, Zhe; Liu, Min; Nie, Shaoping

    2014-01-01

    The objectives of this study were to determine the effects of high-dose and early gestational exposure to zearalenone (ZEN) in female Sprague-Dawley (SD) rats, to correlate the maternal uterus with the fetus, and to explore the development and malformation of fetuses. Pregnant female SD rats were fed diets containing 0.3, 48.5, 97.6, or 146.0 mg/kg ZEN on gestational days (GDs) 0 through 7. All the females survived until GD 20, at which point a cesarean section was performed to harvest the organs, blood, and fetuses. The results indicated that exposure to ZEN during early gestation can impact the maternal reproductive capability. Delayed fetal development was directly linked to maternal toxicity. The toxic effects of ZEN caused early deaths more frequently than late deaths, and the deleterious effects lasted through the end of pregnancy. PMID:24357638

  9. Early maternal separation increases symptoms of activity-based anorexia in male and female rats.

    PubMed

    Hancock, Stephanie; Grant, Virginia

    2009-07-01

    Running activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing the release of stress hormones known to exert anorexic effects. HPA axis reactivity is strongly influenced by early postnatal manipulations, including removal of pups from the dam for short (handling) or prolonged (maternal separation) durations during the preweaning period. The authors examined the effects of handling and maternal separation on food intake, body weight loss, and running rates of young adult male and female rats in the activity-based anorexia (ABA) paradigm. Postnatal treatment did not affect adaptation to a 1-hr restricted feeding schedule before the introduction of wheel running. During the ABA paradigm, maternally separated animals lost weight faster, ate less, ran more, and required fewer days to reach removal criterion compared with handled rats. Females were particularly vulnerable. These findings indicate that early postnatal treatment and sex influence ABA. PMID:19594284

  10. FETAL DEVELOPMENT IN THE RAT FOLLOWING DISRUPTION OF MATERNAL RENAL FUNCTION DURING PREGNANCY

    EPA Science Inventory

    Pregnant Sprague Dawley rats were exposed on either gestation day 7, 9, 11 or 13 to mercuric chloride (1-4 mg/kg, subcutaneously) in order to evaluate maternal renal pathophysiology as a risk factor for abnormal embryonic and fetal development. ollowing exposure, the magnitude an...

  11. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON MATERNAL AND DEVELOPMENTAL THYROID STATUS IN THE RAT

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON MATERNAL AND DEVELOPMENTAL THYROID STATUS IN THE RAT. JR Thibodeaux1, R Hanson1, B Grey1, JM Rogers1, ME Stanton2, and C Lau1. 1Reproductive Toxicology Division; 2Neurotoxicology Division, NHEERL, ORD, US EPA, Research Triangle P...

  12. MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCATANE SULFONATE (PFOS) IN THE RAT

    EPA Science Inventory

    MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT. C. Lau1, J.M. Rogers1, J.R. Thibodeaux1, R.G. Hanson1, B.E. Grey1, B.D. Barbee1, J.H. Richards2, J.L. Butenoff3. 1Reprod. Tox. Div., 2Exp. Tox. Div., NHEERL, USEPA, Research Triangle Park, NC, 3...

  13. MATERNAL HEPATIC AND EMBRYONIC EFFECTS OF 1,2,3,4-TETRACHLOROBENZENE IN THE RAT

    EPA Science Inventory

    To assess possible maternal hepatic and reproductive effects of this uncharged, low molecular weight, lipophilic chlorinated bezene 0,100, 300 and 1000 mg/kg/day of 1,2,3,4,-tetrachlorobenzene (TCB) was orally administered to pregnant rats on days 9 -13 of gestation and the anima...

  14. Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the consequences of maternal Cu (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring dir...

  15. Effect of Himatanthus sucuuba in Maternal Reproductive Outcome and Fetal Anomaly Frequency in Rats.

    PubMed

    de Sousa Soares, Thaigra; Damasceno, Dbora Cristina; Kempinas, Wilma De Grava; Resende, Flvia Mayara Campos; Correa dos Santos, Maria Aparecida; Hiruma-Lima, Cllia Akiko; Volpato, Gustavo Tadeu

    2015-10-01

    The aim of this study was to evaluate the effect of Himatanthus sucuuba on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant rats were randomly divided into three experimental groups as follows: Control = treated with water (vehicle), treated 250 = treated with H. sucuuba at dose 250 mg/kg, and treated 500 = treated with H. sucuuba at dose 500 mg/kg. The rats were orally treated, by gavage, with H. sucuuba or vehicle (water) during preimplantation and organogenic period (from gestational day 0-14). At day 21 of pregnancy, all rats were killed to obtain maternal-fetal data. The treatment with H. sucuuba at dose of 250 mg/kg caused reduction in placental efficiency and an increase preimplantation loss rate and placenta weight compared with the control. The treated 500 group presented a significant decrease in maternal weight gain, maternal weight gain minus gravid uterus weight, fetal weight, and placental efficiency compared with the control. In this group, there was a decrease in body weight at day 20 of pregnancy and metacarpus ossification and an increase in the preimplantation loss rate and skeletal anomalies compared with other groups. Himatanthus sucuuba extract caused intrauterine growth restriction, preimplantation loss, and developmental delay in the high doses tested. PMID:26339763

  16. LATE GESTATIONAL ATRAZINE EXPOSURE DECREASES MATERNAL BEHAVIOR IN LONG-EVANS RATS

    EPA Science Inventory

    Late Gestational Atrazine Exposure Alters Maternal Nursing Behavior in Rats

    Jennifer L. Rayner1 and Suzanne E. Fenton2

    1 University of North Carolina at Chapel Hill, DESE, Chapel Hill, NC, and 2 USEPA/ ORD/NHEERL/Reproductive Toxicology Division, RTP, NC.

    At...

  17. REPEATED MATERNAL SEPARATION IN THE NEONATAL RAT: CELLULAR MECHANISMS CONTRIBUTING TO BRAIN GROWTH SPARING

    EPA Science Inventory

    Separation of rat neonates from their dam has been shown to evoke acutely a variety of biochemical and physiological responses. n the current study, we examined whether these responses were extended to pups who were subject to daily episodes of maternal deprivation, and whether t...

  18. EFFECTS OF CHEMICALLY-INDUCED MATERNAL TOXICITY ON PRENATAL DEVELOPMENT IN THE RAT

    EPA Science Inventory

    The hypothesis that chemically-induced overt maternal toxicity induces a characteristic syndrome of adverse developmental effects in the rat was investigated. regnant animals (Sprague-Dawley strain) were dosed by oral gavage with one of a series of compounds on days 6 through 15 ...

  19. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations

    EPA Science Inventory

    Abstract: The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluorid...

  20. Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

    SciTech Connect

    Lin, G.W.

    1981-01-01

    The distribution of /sup 14/C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed.

  1. Developmental toxicity of benzyl benzoate in rats after maternal exposure throughout pregnancy.

    PubMed

    Koçkaya, E Arzu; Kılıç, Aysun

    2014-01-01

    The maternal and fetal toxicity of benzyl benzoate, commonly used as antiparasitic insecticide, was evaluated in pregnant rats after a daily oral dose of 25 and 100 mg/kg. Biochemical, histopathological, and morphological examinations were performed. Dams were observed for maternal body weights and food and water consumption and subjected to caesarean section on (GD) 20. Maternal and fetal liver, kidney, heart, brain, and placenta were examined histopathologically under light microscope. Maternal and fetal liver and placenta were stained immunohistochemically for vascular endothelial growth factor (VEGF). Morphometric analysis of fetal body lengths, placental measurements, and fetal skeletal stainings was performed. Statistically significant alterations in biochemical parameters and placental and skeletal measurements were determined in treatment groups. In addition to histopathological changes, considerable differences were observed in the immunolocalization of VEGF in treatment groups. These results demonstrated that benzyl benzoate and its metabolites can transport to the placenta and eventually enter the fetuses. PMID:21922633

  2. Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats.

    PubMed

    Fahrbach, S E; Morrell, J I; Pfaff, D W

    1985-06-01

    Intracerebroventricular (i.c.v.) infusions of oxytocin (OXY) induce short-latency maternal behavior in estrogen-primed virgin rats. To investigate if brain OXY might have a role in the onset of maternal behavior at parturition, we have used both antisera to OXY and an analog antagonist of OXY, d(CH2)5-8-ornithine-vasotocin, to reduce the activity of endogenous OXY in a pregnancy-terminated preparation which yields reliable short-latency maternal behavior. Sprague-Dawley rats with lateral ventricle cannulae were ovariectomized and hysterectomized on day 16 of gestation; maternal behavior was stimulated by a s.c. injection of estradiol benzoate (EB). Effects of the i.c.v. infusion of antisera to OXY or of the i.c.v. infusion of d(CH2)5-8-ornithine-vasotocin on the latency to respond to pups were tested by presenting pups 48 h after surgery and EB treatment. Behavioral observations were made for the next 5 h and periodically over the next 5 days. Groups receiving either the antisera to OXY or the analog antagonist had significantly longer latencies to respond to pups than did control groups. In a separate experiment, i.c.v. infusion of d(CH2)5-8-ornithine-vasotocin was shown to have no effect on the performance of maternal behavior in lactating rats 5 days postpartum. These results suggest that OXY may have a role in promoting short-latency maternal behavior in steroid-primed female rats, but that it is probably not involved in sustaining this behavior during lactation. PMID:4010891

  3. Neonatal Maternal Separation Disrupts Regulation of Sleep and Breathing in Adult Male Rats

    PubMed Central

    Kinkead, Richard; Montandon, Gaspard; Bairam, Aida; Lajeunesse, Yves; Horner, Richard

    2009-01-01

    Study Objectives: Neonatal maternal separation (NMS) disrupts development of cardiorespiratory regulation. Adult male rats previously subjected to NMS are hypertensive and show a hypoxic ventilatory response greater than that of controls. These results have been obtained in awake or anesthetised animals, and the consequences of NMS on respiratory control during normal sleep are unknown. This study tested the following hypotheses: NMS augments respiratory variability across sleep-wake states, and NMS-related enhancement of the hypoxic ventilatory response occurs during sleep. Methods: Two groups of adult rats were used: controls (no treatment) and rats subjected to NMS. Ventilatory activity, coefficient of variation, and hypoxic ventilatory response were compared between groups and across sleep-wake states. Subjects: Male Sprague Dawley ratsNMS: n = 11; controls: n = 10. Pups subjected to NMS were isolated from their mother for 3 hours per day from postnatal days 3 to 12. Controls were undisturbed. Measurements and results: At adulthood, sleep-wake states were monitored by telemetry, and ventilatory activity was measured using whole-body plethysmography. Sleep and breathing were measured for 2.5 hours (in the morning) while the rats were breathing room air. Data were analysed in 20-second epochs. Rats were then exposed to a brief (90-sec) hypoxic episode (nadir = 12% O2) to measure the hypoxic ventilatory response. The coefficient of variability for tidal volume and breathing frequency decreased during sleep but remained more elevated in NMS rats than in controls. During non-rapid eye movement sleep, the breathing-frequency response to hypoxia of NMS rats was significantly greater than that of controls. Conclusion: Neonatal maternal seperation results in persistent disruption of respiratory control during sleep. Citation: Kinkead R; Montandon G; Bairam A; Lajeunesse Y; Horner R. Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats. SLEEP 2009;32(12):1611-1620. PMID:20041597

  4. Polyinosinic/Polycytidylic Acid-mediated changes in maternal and fetal disposition of lopinavir in rats.

    PubMed

    Petrovic, Vanja; Piquette-Miller, Micheline

    2015-07-01

    Maintenance of optimal lopinavir (LPV) concentration is essential for effective antiretroviral therapy and prevention of mother-to-child transmission of human immunodeficiency virus. However, little is known about the effects of inflammation on the pharmacokinetics of this protease inhibitor and drug transporter substrate, particularly during gestation. Our objective was to study the effect of polyinosinic/polycytidylic acid [poly(I:C)], a viral mimetic, on key maternal drug transporters, and to examine the effect on maternal and fetal disposition of LPV in rats. Poly(I:C) (5.0 mg/kg i.p.) or saline vehicle was administered to pregnant Sprague-Dawley rats on gestational days 17-18. At 24 hours postinjection, all rats were administered LPV (10 mg/kg i.v.), and plasma and tissues were collected at 5-120 minutes postadministration. Plasma interferon-γ (IFN-γ) levels were measured by enzyme-linked immunosorbent assay, and transporter expression was measured via real-time polymerase chain reaction. Maternal plasma, hepatic, placental, and fetal LPV concentrations were determined by liquid chromatography-tandem mass spectrometry. Administration of poly(I:C) induced IFN-γ plasma levels and downregulated the expression of several important ATP-binding cassette (ABC) drug efflux transporters in the placenta and liver of pregnant rats, compared with controls (P < 0.05). Maternal LPV plasma concentration and area under the concentration-versus-time curve were significantly increased in the poly(I:C) group. Plasma protein binding was also significantly higher in poly(I:C)-treated rats. Pronounced increases in hepatic, placental, and fetal LPV tissue:unbound plasma concentrations were seen in the poly(I:C) group; however, absolute tissue concentrations were not changed. Since the majority of commonly used and clinically important antiretroviral drugs are known to be ABC transporter substrates, inflammation-mediated changes in transporter expression could affect their maternal disposition and fetal exposure. PMID:25887454

  5. Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats

    PubMed Central

    Nephew, Benjamin C.; Bridges, Robert S.

    2008-01-01

    Maternal aggression is a robust type of aggression displayed by lactating female rats. Although arginine vasopressin (AVP) has been implicated in the control of male aggression, its involvement in maternal aggression has not been thoroughly investigated. Previous neuroanatomical studies suggest that AVP may mediate the display of aggression during lactation. In the current study, AVP and an AVP V1a receptor antagonist were centrally administered to primiparous rats on days 5 and 15 of lactation, and aggression, maternal behavior, and grooming were recorded. Although AVP did not affect the number of attacks or duration of aggression, it increased the latency to initiate aggression on day 5, in addition to decreasing maternal behavior and increasing grooming. Conversely, V1a antagonist treatment increased maternal aggression on both days of lactation, decreased maternal behavior on day 15, and decreased grooming on day 5. Thus, it appears that central AVP activity modulates maternal aggression, as well as maternal behavior and grooming behavior during lactation. PMID:18640147

  6. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    PubMed Central

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  7. Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal performance of the rat.

    PubMed

    Sundari, S Bala Tripura; Venu, L; Sunita, Y; Raghunath, M

    2007-07-01

    Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring. PMID:17821855

  8. The different effects of maternal separation on spatial learning and reversal learning in rats.

    PubMed

    Wang, Qiong; Li, Man; Du, Wei; Shao, Feng; Wang, Weiwen

    2015-03-01

    Early postnatal maternal separation (MS) can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4h per day from postnatal day (PND) 1 to 21) on locomotor activity and anxiety behavior in open field, spatial learning and reversal learning in Morris water maze of male and female juvenile (PND 21), adolescent (PND 35) and early adult (PND 56) Wistar rats. The results indicated that MS increased locomotor activity of rats across all ages and reduced anxiety behavior of adolescent rats in open field test. MS also increased swim distance in spatial learning and decreased escape latency in reversal learning in adolescent and early adult rats. Additionally, for socially reared rats, there was increased spontaneous locomotion with age, decreased reversal learning ability with age. The present study provides novel insights into the consequences of MS and demonstrates unique age-dependent changes at the behavioral levels. PMID:25479401

  9. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    SciTech Connect

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-03-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-(1-/sup 14/C)leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy.

  10. Maternal Low Quality Protein Diet Alters Plasma Amino Acid Concentrations of Weaning Rats.

    PubMed

    Kabasakal Cetin, Arzu; Dasgin, Halil; Gülec, Atila; Onbasilar, İlyas; Akyol, Asli

    2015-01-01

    Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring's plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring's plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development. PMID:26633475

  11. Maternal Low Quality Protein Diet Alters Plasma Amino Acid Concentrations of Weaning Rats

    PubMed Central

    Kabasakal Cetin, Arzu; Dasgin, Halil; Gülec, Atila; Onbasilar, İlyas; Akyol, Asli

    2015-01-01

    Several studies have indicated the influence of a maternal low protein diet on the fetus. However, the effect of a maternal low quality protein diet on fetal growth and development is largely unknown. Wistar rats (11 weeks old) were mated and maintained on either a chow diet with 20% casein (n = 6) as the control group (C), or a low quality protein diet with 20% wheat gluten (n = 7) as the experimental group (WG) through gestation and lactation. Maternal body weights were similar in both groups throughout the study. Birth weights were not influenced by maternal diet and offspring body weights during lactation were similar between the groups. Offspring’s plasma amino acid profiles showed that plasma methionine, glutamine and lysine were significantly lower and aspartic acid, ornithine and glycine-proline were significantly higher in the WG. Plant based protein comprises an important part of protein intake in developing countries. It is well-known that these diets can be inadequate in terms of essential amino acids. The current study shows differential effects of a maternal low quality protein diet on the offspring’s plasma amino acids. Future studies will examine further aspects of the influence of maternal low quality protein diets on fetal growth and development. PMID:26633475

  12. Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats.

    PubMed

    Pérez-Laso, C; Ortega, E; Martín, J L R; Pérez-Izquierdo, M A; Gómez, F; Segovia, S; Del Cerro, M C R

    2013-09-01

    The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced "maternal" behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of "maternal" behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups. The present findings provide evidence that prenatal environmental stress can "demasculinize" the behavior, brain anatomy and hormone secretion in the male fetuses expressed when they reach maturity. Moreover, the nature of the maternal care received by neonates can affect the behavior and physiology that they express at maturity. PMID:23994571

  13. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

    PubMed Central

    Sinzato, Yuri Karen; Volpato, Gustavo Tadeu; Iessi, Isabela Lovizutto; Bueno, Aline; Calderon, Iracema de Mattos Paranhos; Rudge, Marilza Vieira Cunha; Damasceno, Dbora Cristina

    2012-01-01

    The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100?mg of streptozotocin/Kg, subcutaneously). At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women. PMID:22778712

  14. Maternal transfer of RSV immunity in cotton rats vaccinated during pregnancy.

    PubMed

    Blanco, Jorge C G; Pletneva, Lioubov M; Oue, Raymonde O; Patel, Mira C; Boukhvalova, Marina S

    2015-10-01

    Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. Although maternal serum antibodies against RSV are efficiently transferred through placenta protecting human infants from RSV-induced disease, this protection is short-lived and the methods for extending and augmenting protection are not known. The objective of this study was to develop an animal model of maternal RSV vaccination using the Sigmodon hispidus cotton rat. Nave or RSV-primed female cotton rats were inoculated with live RSV and set in breeding pairs. Antibody transfer to the litters was quantified and the offspring were challenged with RSV at different ages for analysis of protection against viral replication and lung inflammation. There was a strong correlation between RSV-neutralizing antibody (NA) titers in cotton rat mothers and their pups, which also correlated with protection of litters against virus challenge. Passive protection was short-lived and strongly reduced in animals at 4 weeks after birth. Protection of litters was significantly enhanced by inoculating mothers parenterally with live RSV and inversely correlated with the expression of lung cytokines and pathology. Importantly, vaccination and boosting of nave mothers with the live RSV produced the highest levels of NAs. We conclude that maternal vaccination against RSV in the cotton rat can be used to define vaccine preparations that could improve preexistent immunity and induce subsequent transfer of efficient immunity to infants. PMID:26335771

  15. A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats.

    PubMed

    Sampath, Dayalan; Sabitha, K R; Hegde, Preethi; Jayakrishnan, H R; Kutty, Bindu M; Chattarji, Sumantra; Rangarajan, Govindan; Laxmi, T R

    2014-10-15

    As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus-amygdala-cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions. PMID:25084041

  16. Decreased maternal and fetal cholesterol following maternal bococizumab (anti-PCSK9 monoclonal antibody) administration does not affect rat embryo-fetal development.

    PubMed

    Campion, Sarah N; Han, Bora; Cappon, Gregg D; Lewis, Elise M; Kraynov, Eugenia; Liang, Hong; Bowman, Christopher J

    2015-11-01

    Bococizumab is a humanized monoclonal IgG2?a antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) for the treatment of hyperlipidemia. The evaluation of potential effects on embryo-fetal development was conducted in the rat. In a pharmacokinetic/pharmacodynamic study bococizumab was administered intravenously to pregnant Sprague-Dawley (SD) rats (n=8/group) at 0, 10, 30, and 100mg/kg during organogenesis. Maternal and fetal bococizumab, total cholesterol and HDL concentrations were determined. Bococizumab was well tolerated and there were no effects on ovarian or uterine parameters. Maternal and fetal bococizumab exposure increased with increasing dose, with a corresponding dose-dependent decrease in fetal cholesterol levels. Maternal cholesterol levels were decreased significantly, with reductions that were of a similar magnitude regardless of dose. In the definitive embryo-fetal development study bococizumab was administered to pregnant SD rats (n=20/group) at 0, 10, 30, and 100mg/kg and no adverse maternal or developmental effects were observed up to 100mg/kg. These studies have provided an appropriate and relevant safety assessment of bococizumab in pregnant rats to inform human risk assessment, demonstrating no adverse effects on embryo-fetal development at magnitudes greater than anticipated clinical exposure and in the presence of maximal reductions in maternal cholesterol and dose-dependent reductions in fetal cholesterol. PMID:26382609

  17. Contextual fear conditioning in maternal separated rats: the amygdala as a site for alterations.

    PubMed

    Diehl, Luisa A; Pereira, Natividade de S Couto; Laureano, Daniela P; Benitz, Andr N D; Noschang, Cristie; Ferreira, Andrea G K; Scherer, Emilene B; Machado, Fernanda R; Henriques, Thiago Pereira; Wyse, Angela T S; Molina, Victor; Dalmaz, Carla

    2014-02-01

    The first 2weeks of life are a critical period for neural development in rats. Repeated long-term separation from the dam is considered to be one of the most potent stressors to which rat pups can be exposed, and permanently modifies neurobiological and behavioral parameters. Prolonged periods of maternal separation (MS) usually increase stress reactivity during adulthood, and enhance anxiety-like behavior. The aim of this study was to verify the effects of maternal separation during the neonatal period on memory as well as on biochemical parameters (Na(+), K(+)-ATPase and antioxidant enzymes activities) in the amygdala of adult rats. Females and male Wistar rats were subjected to repeated maternal separation (incubator at 32C, 3h/day) during postnatal days 1-10. At 60days of age, the subjects were exposed to a Contextual fear conditioning task. One week after the behavioral task, animals were sacrificed and the amygdala was dissected for evaluation of Na(+), K(+)-ATPase and antioxidant enzymes activities. Student-t test showed significant MS effect, causing an increase of freezing time in the three exposures to the aversive context in both sexes. Considering biochemical parameters Student-t test showed significant MS effect causing an increase of Na(+), K(+)-ATPase activity in both sexes. On the other hand, no differences were found among the groups on the antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT)] in male rats, but in females, we found a significant MS effect, causing an increase of CAT activity and no differences were found among the groups on SOD and GPx activities. Our results suggest a role of early rearing environment in programming fear learning and memory in adulthood. An early stress experience such as maternal separation may increase activity in the amygdala (as pointed by the increased activity of Na(+), K(+)-ATPase), affecting behaviors related to fear in adulthood, and this effect could be task-specific. PMID:24368626

  18. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

    PubMed

    Sharma, Dyuti; Nkembi, Armande Subayi; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. PMID:26389878

  19. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

    PubMed Central

    Sharma, Dyuti; Subayi Nkembi, Armande; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O2, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O2 (n = 30), PUFA ω-3/air (n = 30), control/O2 (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O2 (n = 30) or to the control/O2 (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. PMID:26389878

  20. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

    PubMed Central

    Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

    2013-01-01

    BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

  1. Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring.

    PubMed

    Lucas, A; Baker, B A; Desai, M; Hales, C N

    1996-10-01

    Epidemiological studies in human show that size in early life is related to blood cholesterol concentrations in adult life, raising the hypothesis that early nutrition programs later lipid metabolism, affecting risk for later vascular disease. Here, we tested the hypothesis that nutrition during pregnancy or lactation in the rat programs lipid metabolism in the offspring, studied in adult life (mean 6 months). Rats (n 35) from normally-fed dams (controls) were compared with (1) rats (n 22) from dams protein-restricted in pregnancy and lactation; (2) rats (n 9) born to normally-fed mother crossed to protein-restricted lactating dams and (3) those (n 9) born of protein-restricted dams and crossed to normally-fed lactating animals. In these latter three groups the offspring showed long-term reduction in plasma cholesterol, HDL-cholesterol and triacylglycerol concentrations compared with controls. The effects were predominantly in males. These findings suggest that in the rat the sensitive period for nutritional programming of cholesterol and triacylglycerol metabolism is both pre- and postnatal (pre-weaning) and that rats may be 'indirectly' programmed by altering the maternal nutritional milieu during gestation or lactation. Whilst it has been hypothesized that early human undernutrition programs risk for vascular disease, one aspect of undernutrition, low maternal protein intake, in this rat model programmed lower plasma cholesterol and triacylglycerol concentrations. PMID:8942366

  2. Cocaine treatment and prenatal environment interact to disrupt intergenerational maternal behavior in rats.

    PubMed

    Johns, Josephine M; Elliott, Deborah L; Hofler, Vivian E; Joyner, Paul W; McMurray, Matthew S; Jarrett, Thomas M; Haslup, Amber M; Middleton, Christopher L; Elliott, Jay C; Walker, Cheryl H

    2005-12-01

    The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience. PMID:16420163

  3. Maternal ileal interpostion surgery confers metabolic improvements to offspring independent of effects on maternal body weight in UCD-T2DM rats

    PubMed Central

    Cummings, Bethany P.; Graham, James L.; Stanhope, Kimber L.; Chouinard, Michael L.; Havel, Peter J.

    2013-01-01

    Introduction Increasing numbers of people are undergoing bariatric surgery, of which approximately half are women in their child-bearing years. However, information on the long-term effects of maternal bariatric surgery in their children is lacking. Furthermore, since bariatric surgery is performed to reduce body weight, clinical studies have not been able to differentiate between benefits to the child due to maternal body weight loss versus other maternal postoperative metabolic changes. Therefore, we used the UCD-T2DM rat model of type 2 diabetes to test the hypothesis that maternal ileal interposition (IT) surgery would confer beneficial metabolic effects in offspring, independent of effects on maternal body weight. Materials and Methods IT surgery was performed on 2-month old prediabetic female UCD-T2DM rats. Females were bred 3 weeks after surgery and male pups were studied longitudinally. Results Maternal IT surgery resulted in decreased body weight in offspring compared with sham offspring (P<0.05). IT offspring exhibited improvements of glucose-stimulated insulin secretion and nutrient-stimulated GLP-2 secretion (P<0.05). Fasting plasma unconjugated bile acid concentrations were 4-fold lower in IT offspring compared with sham offspring at two months of age (P<0.001). Conclusion Overall, maternal IT surgery confers modest improvements of body weight and improves insulin secretion and nutrient-stimulated GLP-2 secretion in offspring in the UCD-T2DM rat model of type 2 diabetes, indicating that this is a useful model for investigating the weight-independent metabolic effects of maternal bariatric surgery. PMID:24036841

  4. Maternal high-fat diet influences stroke outcome in adult rat offspring.

    PubMed

    Lin, ChengCheng; Shao, Bei; Zhou, YuLei; Niu, XiaoTing; Lin, YuanShao

    2016-02-01

    Diet-induced epigenetic modifications in early life could contribute to later health problem. However, it remains to be established whether high-fat diet (HFD) consumption during pregnancy and the suckling period could predispose the offspring to stroke. The present study investigated the influence of maternal HFD on stroke outcome in adult offspring. Female Sprague-Dawley rats were fed a normal diet (5.3% fat) or a HFD (25.7% fat), just before pregnancy until the end of lactation. Male offspring were fed with the control diet or the HFD after weaning, to form four groups (control offspring fed with the control diet (C/C) or the HFD (C/HFD) and offspring of fat-fed dams fed with the control diet (HFD/C) or the HFD (HFD/HFD)). The offspring received middle cerebral artery occlusion on day 120 followed by behavioral tests (neurological deficit score, staircase-reaching test and beam-traversing test), and infarct volumes were also calculated. We found that the HFD/C rats displayed larger infarct volume and aggravated functional deficits (all P<0.05), compared with the C/C rats, indicating that maternal fat-rich diet renders the brain more susceptible to the consequences of ischemic injury. Moreover, maternal HFD offspring displayed elevated glucocorticoid concentrations following stroke, and increased glucocorticoid receptor expression. In addition, adrenalectomy reversed the effects of maternal HFD on stroke outcome when corticosterone was replaced at baseline, but not ischemic, concentrations. Furthermore, expression of brain-derived neurotrophic factor (BDNF) in the ipsilateral hippocampus was decreased in the HFD/C offspring (P<0.05), compared with the C/C offspring. Taken together, maternal diet can substantially influence adult cerebrovascular health, through the programming of central BDNF expression and the hypothalamic-pituitary-adrenal axis. PMID:26643911

  5. Effects of early life social stress on endocrinology, maternal behavior, and lactation in rats

    PubMed Central

    Carini, Lindsay M.; Nephew, Benjamin C.

    2013-01-01

    Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females. The mothers of the rats in the current study were either allowed to raise their pups without exposure to a social stressor (control), or presented with a novel male intruder for 1 hour each day on lactation days 2-16 (chronic social stress). The effects of this early life chronic social stress (CSS) exposure on subsequent peripheral endocrinology, maternal behavior, and physiology were assessed. Exposure of female pups to early life CSS resulted in persistent alterations in maternal endocrinology at the end of lactation (attenuated prolactin and elevated corticosterone), depressed maternal care and aggression, increased restlessness and anxiety-related behavior, impaired lactation, and decreased saccharin preference. The endocrine and behavioral data indicate that early life CSS has long-term effects which are similar to changes seen in clinical populations of depressed mothers, and provide support for the use of the chronic social stress paradigm as an ethologically relevant rodent model for maternal disorders such as postpartum depression and anxiety. PMID:24005186

  6. Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine ?-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning.

    PubMed

    Chmurzynska, Agata; Malinowska, Anna M

    2011-07-01

    The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine ?-synthase, and betaine-homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein-restricted and normal folic acid diet, a protein-restricted and folic acid-supplemented diet, or a normal protein and folic acid-supplemented diet. The progeny were fed either the modified AIN-93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine ?-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P < .001). An interaction effect between the protein and folic acid content in the maternal diet contributed to this down-regulation (P < .001), and the postweaning diet modified these effects. Serum homocysteine concentrations were approximately 15% higher in the male rats (P < .01), but neither prenatal nutrition nor the postweaning diet affected it significantly. We conclude that maternal diet during gestation has an important effect on the transcription level of these 3 genes, but changes in gene expression were not associated with significant changes in progeny homocysteine concentrations. PMID:21840474

  7. Trophoblast Invasion and Blood Vessel Remodeling Are Altered in a Rat Model of Lifelong Maternal Obesity

    PubMed Central

    Hayes, Emily K.; Tessier, Daniel R.; Percival, Michael E.; Holloway, Alison C.; Petrik, Jim J.; Gruslin, Andree

    2014-01-01

    Maternal obesity is associated with an increased risk of a number of pregnancy complications, including fetal demise, which may be linked to impaired placental development as a result of altered trophoblast invasion and vessel remodeling. Therefore, we examined these parameters in pregnant rats fed a control (normal weight) or high fat (HF) diet (obese) at 2 critical times of rat placental development. Early trophoblast invasion was increased by approximately 2-fold in HF-fed dams with a concomitant increase in the expression of matrix metalloproteinase 9 protein, a mediator of tissue remodeling and invasion. Furthermore, we observed significantly higher levels of smooth muscle actin surrounding the placental spiral arteries of HF-fed dams, suggesting impaired spiral artery remodeling. Taken together, the results of this study suggest that altered placental development is an important contributor to the poor pregnancy outcomes and increased fetal demise in our model of lifelong maternal obesity. PMID:24155067

  8. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats

    PubMed Central

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-01-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2′-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity. PMID:26730379

  9. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats.

    PubMed

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-12-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2'-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity. PMID:26730379

  10. 26Al incorporation into the tissues of suckling rats through maternal milk

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Nagai, H.; Kobayashi, K.; Tada, W.; Horikawa, T.; Matsuzaki, H.

    2004-08-01

    Aluminium (Al) is highly neurotoxic and inhibits prenatal and postnatal development of the brain in humans and experimental animals. However, Al incorporation into the brain of sucklings through maternal milk has not yet been well clarified because Al lacks a suitable isotope for radioactive tracer experiments. Using 26Al as a tracer, we measured 26Al incorporation into the brain of suckling rats by accelerator mass spectrometry. Lactating rats were subcutaneously injected with 26AlCl3 from day 1 to day 20 postpartum. Suckling rats were weaned from day 21 postpartum. From day 5 to day 20 postpartum, the 26Al levels measured in the brain, liver, kidneys and bone of suckling rats increased significantly. After weaning, the amounts of 26Al in the liver and kidneys decreased remarkably. However, the 26Al amount in the brain had diminished only slightly up to 140 days after weaning.

  11. Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life.

    PubMed

    Tarry-Adkins, Jane L; Chen, Jian-Hua; Jones, Richard H; Smith, Noel H; Ozanne, Susan E

    2010-08-01

    Low birth weight is associated with glucose intolerance, insulin resistance, and type 2 diabetes (T2D) in later life. Good evidence indicates that the environment plays an important role in this relationship. However, the mechanisms underlying these relationships are defined poorly. Islets are particularly susceptible to oxidative stress, and this condition combined with fibrosis is thought to be instrumental in T2D pathogenesis. Here we use our maternal low-protein (LP) rat model to determine the effect of early diet on oxidative stress and fibrosis in pancreatic islets of male offspring at 3 and 15 mo of age. Islet xanthine oxidase (XO) expression was increased in 15-mo LP offspring, which suggests increased oxidative-stress. Manganese superoxide-dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and heme oxygenase-1 (HO-1) (antioxidant enzymes) were reduced significantly in LP offspring, which indicated impairment of oxidative defense. Expression of fibrosis markers collagen I and collagen III also increased in 15-mo LP offspring. Angiotensin II receptor type I (AT(II)R(1)), induced by hyperglycemia and oxidative-stress, was significantly up-regulated in 15-mo LP offspring. Lipid peroxidation was also increased in 15-mo LP animals. We conclude that maternal protein restriction causes age-associated increased oxidative stress, impairment of oxidative defense, and fibrosis. These findings provide mechanisms by which suboptimal early nutrition can lead to T2D development later in life. PMID:20388698

  12. Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in Cafeteria Diet-induced Obese Rats.

    PubMed

    Benaissa, Nawel; Merzouk, Hafida; Merzouk, Sid Ahmed; Narce, Michel

    2015-04-01

    Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil (5%) for 1 month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns. PMID:25966756

  13. Changes in memory and synaptic plasticity induced in male rats after maternal exposure to bisphenol A.

    PubMed

    Wang, Chong; Niu, Ruiyan; Zhu, Yuchen; Han, Haijun; Luo, Guangying; Zhou, Bingrui; Wang, Jundong

    2014-08-01

    Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to adversely impact the central nervous system, especially with respect to learning and memory. However, the precise effect and specific mechanisms have not been fully elucidated. In the present study, pregnant Sprague-Dawley rats were orally administered with BPA at 0.05, 0.5, 5 or 50mg/kgbody weight (BW) per day from embryonic day 9 (E 9) to E 20. We examined the effects of maternal BPA exposure on memory and synaptic structure in the hippocampus of male offspring at postnatal day (PND) 21. Maternal BPA exposure significantly affected locomotor activity, exploratory habits, and emotional behavior in open field test, and increased reference and especially working memory errors in the radial arm maze during the postnatal developing stage. Maternal BPA exposure had an adverse effect on synaptic structure, including a widened synaptic cleft, a thinned postsynaptic density (PSD), unclear synaptic surface and disappeared synaptic vesicles. Furthermore, maternal BPA exposure decreased the mRNA and protein expressions of synaptophysin, PSD-95, spinophilin, GluR1 and NMDAR1 in the hippocampus of male offspring on PND 21. These results showed that fetal growth and development was more sensitive to BPA exposure. The decreased learning and memory induced by maternal exposure to BPA in this study may be involved in synaptic plasticity alteration. PMID:24820113

  14. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  15. Impact of Experimental Diabetes on the Maternal Uterine Vascular Remodeling During Rat Pregnancy

    PubMed Central

    Phillips, Julie K.; Vance, Amanda M.; Raj, Renju S.; Mandal, Maurizio; Linder, Erika A.; Gokina, Natalia I.

    2012-01-01

    Normal pregnancy is associated with an increase in uteroplacental blood flow in part due to growth and remodeling of the maternal uterine vasculature. In this study, we characterized the effect of diabetic pregnancy on vascular growth of the maternal uterine vasculature and on the passive mechanical properties of the uterine resistance arteries. Diabetes was induced in pregnant rats by injection of streptozotocin and confirmed by development of hyperglycemia. Fetuses of diabetic rats were significantly smaller and placentas larger compared to controls. Pregnancy-induced axial elongation of the mesometrial uterine vasculature was not altered by diabetes. Vascular wall thickness was unchanged between groups. Wall distensibility was increased and the rate constant of an exponential function fitted to stressstrain curve was significantly reduced demonstrating decreased wall stiffness in diabetic uterine radial arteries compared to controls. We conclude that experimental diabetes in rat pregnancy does not compromise the growth of maternal uterine vasculature but alters passive mechanical properties of the uterine radial arteries. PMID:22383782

  16. Olfactory and vomeronasal system mediation of maternal recognition in the developing rat.

    PubMed

    Teicher, M H; Shaywitz, B A; Lumia, A R

    1984-01-01

    Olfactory-mediated arousal and maternal recognition were evaluated in neonatal rat pups. Non-nutritionally deprived pups which underwent bilateral olfactory bulbectomies on day 5, failed to distinguish between the ventral and dorsal surfaces of a nursing rat and a heating pad. They showed virtually no arousal response to any of these surfaces. In contrast, pups with unilateral bulbectomies, and sham controls, graded their arousal response, and were maximally aroused by the mother's ventral surface. Following 24 h of maternal deprivation, bilaterally bulbectomized pups displayed a modest arousal response, directed primarily towards the dorsal surface. Pups with complete vomeronasal nerve sections displayed maximal arousal responses toward the dorsal surface. However, they were far more aroused than the bilaterally bulbectomized pups. Rat pups with incomplete vomeronasal lesions graded their response like controls, with maximal responsiveness directed toward the ventral surface. Shaving the dorsal surface markedly diminished the arousal response of bilaterally bulbectomized pups, but had only modest effects on sham and unilaterally bulbectomized controls. Thus, lesions that destroyed both the main and accessory's olfactory bulb systems severely impaired the pups' ability to effectively recognize a lactating female and markedly diminished maternally-induced arousal. Selective damage to the vomeronasal-accessory olfactory system appeared to disrupt discriminative capacity, but had little effect on the magnitude of the arousal response. PMID:6697259

  17. Deconstructing the function of maternal stimulation in offspring development: Insights from the artificial rearing model in rats.

    PubMed

    Lomanowska, Anna M; Melo, Angel I

    2016-01-01

    This article is part of a Special Issue on "Parental Care". Maternal behavior has an important function in stimulating adequate growth and development of the young. Several approaches have been used in primates and rodents to deconstruct and examine the influence of specific components of maternal stimulation on offspring development. These approaches include observational studies of typical mother-infant interactions and studies of the effects of intermittent or complete deprivation of maternal contact. In this review, we focus on one unique approach using rats that enables the complete control of maternal variables by means of rearing rat pups artificially without contact with the mother or litter, while maintaining stable nutrition, temperature and exposure to stressful stimuli. This artificial rearing model permits the removal and controlled replacement of relevant maternal and litter stimuli and has contributed valuable insights regarding the influence of these stimuli on various developmental outcomes. It also enables the analysis of factors implicated in social isolation itself and their long-term influence. We provide an overview of the effects of artificial rearing on behavior, physiology, and neurobiology, including the influence of replacing maternal tactile stimulation and littermate contact on these outcomes. We then discuss the relevance of these effects in terms of the maternal role in regulating different aspects of offspring development and implications for human research. We emphasize that artificial rearing of rats does not lead to a global insult of nervous system development, making this paradigm useful in investigating specific developmental effects associated with maternal stimulation. PMID:26112882

  18. Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

    PubMed

    Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M

    2015-01-01

    The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel. PMID:25791846

  19. Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth1

    PubMed Central

    Tarry-Adkins, Jane L; Fernandez-Twinn, Denise S; Hargreaves, Iain P; Neergheen, Viruna; Aiken, Catherine E; Martin-Gronert, Malgorzata S; McConnell, Josie M; Ozanne, Susan E

    2016-01-01

    Background: It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined. Objectives: We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype. Design: A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed “recuperated”). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase–polymerase chain reaction. Results: Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01). Conclusions: Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was associated with higher indexes of oxidative stress and inflammation and hyperinsulinemia. CoQ10 supplementation prevented liver fibrosis accompanied by downregulation of oxidative stress, inflammation, and hyperinsulinemia. PMID:26718412

  20. Fetal and maternal effects of continual exposure of rats to 970-MHz circularly polarized microwaves

    SciTech Connect

    Berman, E.; Weil, C.; Phillips, P.A.; Carter, H.B.; House, D.E.

    1992-01-01

    Virtually continual exposure to970-MHz microwaves in circularly-polarized waveguides was used to elicit fetal responses in Sprague-Dawley rats during gestation. Two hundred fifty rats were exposed to microwave radiation at whole-body averaged specific absorption rates (SAR) of 0.07, 2.4, or 4.8 W/kg, or concurrently sham-irradiated for 22 h/day from the 1st through the 19th day of gestation. At SAR of 4.8 W/kg, only fetal body weight was significantly altered (-12%, P=.012). Two of twelve rats died during the exposure at SAR of 4.8 W/kg. Bred, but non-pregnant, rats that were exposed at SAR of 4.8 W/kg had significantly lower body weight gain than sham-irradiated rats; similar lower gain is assumed to have occurred in the pregnant rats exposed at SAR of 4.8 W/kg, and whose fetuses were significantly smaller. The authors conclude that continual gestational exposure at SAR of 4.8 (but not 2.4 or lower) W/kg induces fetal alterations. Apparently, deleterious maternal effects are associated with these fetal changes. Although colonic temperature was not measured in these rats, it is expected that exposure at 4.8 W/kg was hyperthermal.

  1. Maternal High Fat Diet Programs Rat Offspring Hypertension and Activates the Adipose Renin-Angiotensin System

    PubMed Central

    GUBERMAN, Cristiane; JELLYMAN, Juanita K.; HAN, Guang; ROSS, Michael G.; DESAI, Mina

    2014-01-01

    Objective Maternal high fat diet programs an increased risk of offspring obesity and systemic hypertension. Although the renal renin-angiotensin system (RAS) is known to regulate blood pressure, it is now recognized that the RAS is also activated in adipose tissue during obesity. We hypothesized that programmed offspring hypertension is associated with activation of the adipose tissue RAS in the offspring of obese rat dams. Study Design At 3 weeks of age, female rats were weaned to a high fat (HF: 60% k/cal; n=6) or control (control, 10% k/cal; n=6) diet. At 11 weeks of age, these rats were mated and continued on their respective diets during pregnancy. After birth, at 1 day of age, subcutaneous adipose tissue was collected, litter size was standardized and pups were cross-fostered to either control or HF dams, creating 4 study groups. At 21 days of age, offspring were weaned to control or HF diet. At 6 months of age, body fat and blood pressure were measured. Thereafter, subcutaneous and retroperitoneal adipose tissue was harvested from male offspring. Protein expression of adipose tissue RAS components were determined by Western Blotting. Results Maternal high fat diet induced early and persistent alterations in offspring adipose RAS components. These changes were dependent upon the period of exposure to the maternal high fat diet, were adipose tissue specific (subcutaneous and retroperitoneal), and were exacerbated by a postnatal high fat diet. Maternal high fat diet increased adiposity and blood pressure in offspring, regardless of the period of exposure. Conclusion These findings suggest that programmed adiposity and activation of the adipose tissue RAS are associated with hypertension in offspring of obese dams. PMID:23743273

  2. Angiotensin II is required to induce exaggerated salt sensitivity in Dahl rats exposed to maternal separation

    PubMed Central

    Loria, Analia S; Pollock, David M; Pollock, Jennifer S

    2015-01-01

    We previously reported that maternal separation, rat model of early life stress, enhances pressor responses to acute and chronic stressors. The aims of this study were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show exaggerated blood pressure responses to acute behavioral stressors, such as restraint stress or air jet stress (AJS), or, hypertensive stimuli including chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200ng/Kg/min) during 1week. MatSep was performed in male DS rats for 3h/day from postnatal days 214. At 8weeks of age, rats were implanted with telemetry transmitters and allowed to recover. Mean arterial pressure (MAP) was not different between MatSep-DS and Ctl-DS rats at baseline (1202mmHg vs. 1181mmHg, n=48). Blood pressure responses during AJS and restraint stress were not different between MatSep-DS and Ctl-DS at 3min. However, blood pressure recovery from AJS was significantly impaired in MatSep-DS rats compared to Ctl-DS rats (P<0.05). 3-h stress-induced similar responses in MatSep and Ctl-DS rats. Chronic blood pressure responses to AngII infusion in rats fed a high-salt diet displayed enhanced MAP in MatSep-DS when compared with Ctl-DS rats (1675mmHg vs. 1522mmHg, pinteraction <0.05). However, MAP increased similarly in both groups in response to AngII infusion or high-salt diet separately. Renal parameters such as proteinuria, urine flow rate, and urine electrolytes were not different between groups in response to each treatment. In summary, salt sensitivity induces exaggerated blood pressor responses only in presence of AngII due to early life stress. PMID:25999404

  3. Effect of cocaine on periadolescent rats with or without early maternal separation.

    PubMed

    Planeta, C S; Marin, M T

    2002-11-01

    Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33 degrees C) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. On day 6 all animals received saline. On day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period. PMID:12426637

  4. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    SciTech Connect

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  5. Repeated brief postnatal maternal separation enhances hypothalamic gastric autonomic circuits in juvenile rats

    PubMed Central

    Banihashemi, Layla; Rinaman, Linda

    2009-01-01

    Maternal separation of rat pups for 15 minutes each day over the first one to two postnatal weeks (MS15) has been shown to increase the active maternal care received by pups and to decrease their later neuroendocrine and behavioral stress reactivity compared to non-separated (NS) controls. Stress responses prominently feature altered gastric secretion and motility, and we previously reported that the developmental assembly of forebrain circuits underlying gastric autonomic control, including gastric responses to stress, is delayed by MS15 in neonatal rats (Card et al. 2005, J. Neurosci. 25(40): 9102). To determine how this early delay affects the later organization of central gastric autonomic circuits, the present study examined the effects of neonatal MS15 on central pre-gastric circuits assessed in post-weaning, juvenile rats. For this purpose, the retrograde transynaptic viral tracer, pseudorabies virus (PRV), was microinjected into the stomach wall of 2830 day old male rats with an earlier developmental history of either MS15 or NS. Rats were perfused 72 hours later and tissue was processed to reveal PRV-positive cells. Transynaptic PRV immunolabeling was quantified in selected preautonomic brainstem and forebrain regions, including the area postrema, bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular nucleus of the hypothalamus (PVN), and visceral cortices. Compared to NS controls, MS15 rats displayed a significantly greater amount of PRV labeling within the PVN, including both the dorsal cap and ventral subnuclei. There were no postnatal group differences in the amount of PRV labeling within any other brain region examined in this study. This effect of MS15 to enhance hypothalamic preautonomic circuit structure indicates a strengthening of this pathway and may provide insight into how early life experience produces differential effects on later stress reactivity, including gastric secretory and motor responses to stress. PMID:19800939

  6. The influence of natural variations in maternal care on play fighting in the rat.

    PubMed

    Parent, Carine I; Meaney, Michael J

    2008-12-01

    Naturally occurring variations in maternal care in the rat influence the sensitivity of offspring to stress in adulthood. The offspring of mothers that show lower levels of pup licking/grooming (i.e., low-LG mothers) demonstrate enhanced responses to stress and increased anxiety compared to those of high-LG mothers. Low-LG offspring are also more sensitive to the influence of environmental enrichment than high-LG offspring. This study examined play fighting in the juvenile offspring of high-LG and low-LG dams in a multiple-play partners housing environment. Male offspring from low-LG dams demonstrated a significantly higher frequency of pouncing, pinning and aggressive social grooming than did high-LG males and high-LG and low-LG females. Consistent with earlier reports, male pups engaged in more play fighting than did females and maternal care was associated with differences in play fighting but only in males. Lower levels of stimulation in the form of LG from the dam during perinatal development may thus increase sensitivity for the stimulating effects of play behavior in periadolescence, in part explaining the increased solicitation of play fighting through increased pouncing in the male offspring of the low-LG mothers. These findings identify a possible influence of variations in maternal care on play fighting and suggest that maternal care in the perinatal period influence social interactions during periadolescence. PMID:18846499

  7. Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Daunton, N. G.; Wade, C. E.

    2001-01-01

    A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.

  8. A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats

    PubMed Central

    Liu, Ji-Long; Wang, Tong-Song; Zhao, Miao; Peng, Ying; Fu, Yong-Sheng

    2015-01-01

    Thyroid disorders are relatively frequently observed in pregnant women. However, the impact of pregnancy on maternal thyroid has not been systematically evaluated. In the present study, using the rat as an animal model, we observed that the weight of maternal thyroid increased by about 18% in late pregnancy. To gain an insight into the molecular mechanisms, we took advantage of RNA-seq approaches to investigate global gene expression changes in the maternal thyroid. We identified a total of 615 differentially expressed genes, most of which (558 genes or 90.7%) were up-regulated in late pregnancy compared to the non-pregnant control. Gene ontology analysis showed that genes involved in cell cycle and metabolism were significantly enriched among up-regulated genes. Unexpectedly, pathway analysis revealed that expression levels for key components of the thyroid hormone synthesis pathway were not significantly altered. In addition, by examining of the promoter regions of up-regulated genes, we identified MAZ (MYC-associated zinc finger protein) and TFCP2 (transcription factor CP2) as two causal transcription factors. Our study contributes to an increase in the knowledge on the maternal thyroid adaptation to pregnancy. PMID:26580608

  9. Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

    PubMed Central

    Aksi?, Milan; Radonji?, Nevena V.; Aleksi?, Dubravka; Jevti?, Gordana; Markovi?, Branka; Petronijevi?, Nataa; Radonji?, Vidosava; Filipovi?, Branislav

    2014-01-01

    Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24?h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition. PMID:24895554

  10. Behavioural and biochemical changes in maternally separated Sprague-Dawley rats exposed to restraint stress.

    PubMed

    van Zyl, P J; Dimatelis, J J; Russell, V A

    2016-02-01

    Early life adversity has been associated with the development of various neuropsychiatric disorders in adulthood such as depression and anxiety. The aim of this study was to determine if stress during adulthood can exaggerate the depression-/anxiety-like behaviour observed in the widely accepted maternally separated (MS) Sprague-Dawley (SD) rat model of depression. A further aim was to determine whether the behavioural changes were accompanied by changes in hippocampal brain-derived neurotrophic factor (BDNF) and the protein profile of the prefrontal cortex (PFC). Depression-/anxiety-like behaviour was measured in the elevated plus maze, open field and forced swim test (FST) in the MS SD rats exposed to chronic restraint stress in adulthood. As expected, MS increased immobility of SD rats in the FST but restraint stress did not enhance this effect of MS on SD rats. A proteomic analysis of the PFC revealed a decrease in actin-related proteins in MS and non-separated rats subjected to restraint stress as well as a decrease in mitochondrial energy-related proteins in the stressed rat groups. Since MS during early development causes a disruption in the hypothalamic-pituitary-adrenal axis and long-term changes in the response to subsequent stress, it may have prevented restraint stress from exerting its effects on behaviour. Moreover, the decrease in proteins related to mitochondrial energy metabolism in MS rats with or without subsequent restraint stress may be related to stress per se and not depression-like behaviour, because rats subjected to restraint stress displayed similar decreases in energy-related proteins and spent less time immobile in the FST than control rats. PMID:26555398

  11. Metyrapone Blocks Maternal Food Restriction-Induced Changes in Female Rat Offspring Lung Development

    PubMed Central

    Li, Yishi; Corral, Julia; Saraswat, Aditi; Husain, Sumair; Dhar, Ankita; Sakurai, Reiko; Khorram, Omid; Torday, John S.

    2014-01-01

    Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood. PMID:24023031

  12. Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring.

    PubMed

    Cassella, Sarah N; Hemmerle, Ann M; Lundgren, Kerstin H; Kyser, Tara L; Ahlbrand, Rebecca; Bronson, Stefanie L; Richtand, Neil M; Seroogy, Kim B

    2016-03-01

    Activation of the maternal innate immune system, termed "maternal immune activation" (MIA), represents a common environmental risk factor for schizophrenia. Whereas evidence suggests dysregulation of GABA systems may underlie the pathophysiology of schizophrenia, a role for MIA in alteration of GABAergic systems is less clear. Here, pregnant rats received either the viral mimetic polyriboinosinic-polyribocytidilic acid or vehicle injection on gestational day 14. Glutamic acid decarboxylase-67 (GAD67) mRNA expression was examined in male offspring at postnatal day (P)14, P30 and P60. At P60, GAD67 mRNA was elevated in hippocampus and thalamus and decreased in prefrontal cortex of MIA offspring. MIA-induced alterations in GAD expression could contribute to the pathophysiology of schizophrenia. PMID:26830319

  13. Effects of maternal ethanol ingestion on uptake of glucose alanine analogs in fetal rats

    SciTech Connect

    Snyder, A.K.; Singh, S.P.; Pullen, G.L.

    1986-05-01

    The distribution of maternally-derived glucose and alanine has been studied in selected tissues of fetuses from ethanol-fed (EF) rats (30% of caloric intake throughout gestation). Controls received diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation, 2 ..mu..Ci /sup 3/H 2-deoxyglucose (DG) and 1 ..mu..Ci /sup 14/C ..cap alpha..-aminoisobutyric acid (AIB) were administered i.v. to each rat. One hour later, maternal blood, placenta, and fetal blood, liver, lung and brain were sampled for /sup 3/H and /sup 14/C activities. When compared to either control group, the mean /sup 14/C AIB activities of tissues from EF animals were reduced from 19 to 46%, with the greatest effect seen in the brain (3.7 +/- 0.1, 7.2 +/- 0.3 and 6.9 +/- 1.3 dpm/mg in EF, PF and AF fetuses respectively). In addition, the ratios of tissue:plasma /sup 14/C were reduced (p < 0.01 or lower) in the EF fetal tissues and placenta. Maternal ethanol ingestion reduced the /sup 3/H 2-DG content of placenta (p < 0.05) and of brain (38.6 + 1.2, 48.1 +/- 1.2 and 47.2 +/- 1.2 in EF, PF and AF, p < 0.001). Brain weight showed significant positive correlations with AIB content (r = 0.466, p < 0.001) and with 2-DG content (r = 0.267, p < 0.01). Impaired uptake of maternally-derived nutrients may play a significant role in the effects of ethanol in utero.

  14. Effect of advanced maternal age on pregnancy outcomes and vascular function in the rat.

    PubMed

    Care, Alison S; Bourque, Stephane L; Morton, Jude S; Hjartarson, Emma P; Davidge, Sandra T

    2015-06-01

    Advanced maternal age is becoming increasingly common in Western societies and is associated with increased maternal and fetal morbidity and mortality. We hypothesized that aging results in impaired vascular function in pregnancy because of increased vascular oxidative stress and resultant scavenging of nitric oxide in both uterine and systemic arteries, causing reduced uteroplacental perfusion and poor pregnancy outcomes. Using aged rats (9.5 months), we investigated the effect of a delayed first natural pregnancy on pregnancy outcomes and uterine and mesenteric artery function on gestational day 20. Delayed pregnancy in the rat reduced fertility by 46%, reduced litter size by 36%, caused fetal growth restriction, increased placental weight, and increased maternal systolic blood pressure (by 16 mm Hg). Uterine arteries from aged dams displayed reduced constriction to phenylephrine (young: 14.3±0.94 mN/mm versus aged: 11.4±0.5 mN/mm, P=0.02) and potassium chloride (124 mmol/L; young: 21.8±1.27 mN/mm versus aged: 14.2±1.7 mN/mm; P=0.01). Methacholine-induced vasodilation was similar in uterine arteries from young and aged dams. However, mesenteric arteries from aged dams had a greater nitric oxide and a reduced endothelial-derived hyperpolarization contribution to methacholine-mediated vasodilation compared with young dams. Both uterine and mesenteric arteries from aged dams had greater active myogenic responses, with area under the curve increased by 228% and 151%, in aged uterine and mesenteric arteries, respectively. These results demonstrate that vascular function is altered at an advanced maternal age and provides further insights into the risks of poor pregnancy outcomes observed in women who delay pregnancy. PMID:25916720

  15. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats

    PubMed Central

    Tong, Wenni; Xue, Qin; Li, Yong

    2011-01-01

    Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The present study tested the hypothesis that maternal hypoxia results in reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar collagen matrix in the developing heart. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from 21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio was increased in E21 but not in PD7. Left ventricular myocardium wall thickness and cardiomyocyte proliferation were significantly decreased in both fetal and neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal heart, but significantly increased the collagen content in the neonatal heart. Western blotting revealed that maternal hypoxia significantly increased collagen I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and MMP-9 levels and activities were not altered in either fetal or neonatal hearts. Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3 and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were not affected. The results demonstrate that in utero hypoxia reprograms the expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with the increased collagen deposition in the developing heart. PMID:21856922

  16. Taurine attenuates maternal and embryonic oxidative stress in a streptozotocin-diabetic rat model.

    PubMed

    Shivananjappa, Mahesh Mysore; Muralidhara

    2012-05-01

    Oxidative stress mechanisms have been implicated in congenital anomalies and morbidity/mortality of fetus/newborn in diabetic pregnancy. Numerous antioxidant treatments have shown varied beneficial effects in improving both maternal and fetal outcomes. The present study examined the propensity of taurine to attenuate the degree of embryopathy and oxidative stress among pregnant diabetic rats. Adult rats (CFT-Wistar) were rendered diabetic with an acute dose of streptozotocin (STZ; 45 mg/kg bodyweight) on gestation day (GD) 4. Both Diabetic and non-diabetic dams were given oral supplements of taurine (0.5 and 1g/kg bodyweight/day) from GD 5 to GD 12. Maternal diet intake, bodyweight gain and urine output were monitored and dams were killed on GD 13. Markers of oxidative stress were determined in embryos and maternal livers. STZ treatment induced marked embryopathy (32%) and taurine supplements markedly reduced the degree of embryopathy (54% protection). The STZ-induced higher oxidative stress was significantly attenuated in rats given taurine supplements (P<0.05) and a similar effect was seen in embryos (P<0.05). These data suggest that dietary taurine during pregnancy provides significant protection against diabetes-induced oxidative stress in both the mother and the embryos and thus may serve as a therapeutic supplement during diabetic pregnancy. Diabetes during pregnancy affects >5% of all pregnancies, causing reproductive abnormalities that enhance spontaneous abortion - congenital anomalies, morbidity and mortality of both mother and fetus/newborn. One of the major mechanisms is increased oxidative stress caused by hyperglycaemia and the most prominent anti-teratogenic effect was achieved using antioxidative agents. Management of oxidative stress is considered, along with tight glycaemic control, to be beneficial both before conception and during pregnancy. Taurine, a ubiquitous amino acid found in almost all mammalian tissues, constitutes more than 50% of free amino acids. The aim of the study was to determine whether oral taurine supplementation given to pregnant diabetic rats during the post-implantation period could reduce embryo lethality and protect the developing embryos against maternal hyperglycaemia-induced oxidative stress. Adult rats were rendered diabetic with an acute dose of streptozotocin on gestation day (GD) 4. Both diabetic and non-diabetic dams were administered oral taurine for a period of 8 days (GD 5-13). Maternal diet intake, bodyweight gain and urine output were monitored and dams were killed on GD 13. Markers of oxidative stress and antioxidant defences were studied in embryos and maternal livers. STZ induced marked embryopathy (32%) and taurine supplementation offered significant protection (54%). Taurine significantly offset diabetes-associated oxidative stress in the embryos of diabetic rats. These data suggest that dietary taurine supplementation during pregnancy provides significant protection against diabetes-induced oxidative stress both in mother and embryos and thus may serve as a therapeutic supplement under diabetic pregnancy. PMID:22414371

  17. Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood

    PubMed Central

    Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

    2015-01-01

    Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis. PMID:25713634

  18. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

    Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-?, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings show that long-term effects of maternal ID and prenatal LPS were additive, such that offspring exposed to both insults displayed more adult behavioral abnormalities than offspring exposed to one alone. PMID:24930842

  19. Exposure to repeated maternal aggression induces depressive-like behavior and increases startle in adult female rats

    PubMed Central

    Bourke, Chase H.; Neigh, Gretchen N.

    2011-01-01

    The stress response is a multifaceted physiological reaction that engages a wide range of systems. Animal studies examining stress and the stress response employ diverse methods as stressors. While many of these stressors are capable of inducing a stress response in animals, a need exists for an ethologically relevant stressor for female rats. The purpose of the current study was to use an ethologically relevant social stressor to induce behavioral alterations in adult female rats. Adult (postnatal day 90) female Wistar rats were repeatedly exposed to lactating Long Evans female rats to simulate chronic stress. After six days of sessions, intruder females exposed to defeat were tested in the sucrose consumption test, the forced swim test, acoustic startle test, elevated plus maze, and open field test. At the conclusion of behavioral testing, animals were restrained for 30 minutes and trunk blood was collected for assessment of serum hormones. Female rats exposed to maternal aggression exhibited decreased sucrose consumption, and impaired coping behavior in the forced swim test. Additionally, female rats exposed to repeated maternal aggression exhibited an increased acoustic startle response. No changes were observed in female rats in the elevated plus maze or open field test. Serum hormones were unaltered due to repeated exposure to maternal aggression. These data indicate the importance of the social experience in the development of stress-related behaviors: an acerbic social experience in female rats precipitates the manifestation of depressive-like behaviors and an enhanced startle response. PMID:22093902

  20. Maternal care affects the phenotype of a rat model for schizophrenia

    PubMed Central

    van Vugt, Ruben W. M.; Meyer, Francisca; van Hulten, Josephus A.; Vernooij, Jeroen; Cools, Alexander R.; Verheij, Michel M. M.; Martens, Gerard J. M.

    2014-01-01

    Schizophrenia is a complex mental disorder caused by an interplay between genetic and environmental factors, including early postnatal stressors. To explore this issue, we use two rat lines, apomorphine-susceptible (APO-SUS) rats that display schizophrenia-relevant features and their phenotypic counterpart, apomorphine-unsusceptible (APO-UNSUS) rats. These rat lines differ not only in their gnawing response to apomorphine, but also in their behavioral response to novelty (APO-SUS: high, APO-UNSUS: low). In this study, we examined the effects of early postnatal cross-fostering on maternal care and on the phenotypes of the cross-fostered APO-SUS and APO-UNSUS animals later in life. Cross-fostered APO-UNSUS animals showed decreased body weights as pups and decreased novelty-induced locomotor activity as adults (i.e., more extreme behavior), in accordance with the less appropriate maternal care provided by APO-SUS vs. their own APO-UNSUS mothers (i.e., the APO-SUS mother displayed less non-arched-back nursing and more self-grooming, and was more away from its nest). In contrast, cross-fostered APO-SUS animals showed increased body weights as pups and reduced apomorphine-induced gnawing later in life (i.e., normalization of their extreme behavior), in line with the more appropriate maternal care provided by APO-UNSUS relative to their own APO-SUS mothers (i.e., the APO-UNSUS mother displayed more non-arched-back nursing and similar self-grooming, and was not more away). Furthermore, we found that, in addition to arched-back nursing, non-arched-back nursing was an important feature of maternal care, and that cross-fostering APO-SUS mothers, but not cross-fostering APO-UNSUS mothers, displayed increased apomorphine-induced gnawing. Thus, cross-fostering not only causes early postnatal stress shaping the phenotypes of the cross-fostered animals later in life, but also affects the phenotypes of the cross-fostering mothers. PMID:25157221

  1. Maternal separation affects cocaine-induced locomotion and response to novelty in adolescent, but not in adult rats.

    PubMed

    Marin, Marcelo T; Planeta, Cleopatra S

    2004-07-01

    Maternal separation is known to exert long-term effects on both behavior and the neuroendocrine system. We investigated cocaine-induced locomotor activation as well as the locomotor and corticosterone response to forced novelty in maternally separated adolescent and adult rats. Maternal separation consisted of separating litters from their dams daily during 5 h from postnatal days 2 to 6. Control animals were subjected only to regular cage changes. Cocaine- (10 mg/kg, i.p.) and novelty-induced locomotion were recorded in an activity cage. After the animals were tested for behavioral response to novelty, trunk blood samples were collected and plasma corticosterone levels were determined by radioimmunoassay. Adolescent rats exposed to maternal separation exhibited an increased locomotor response to novelty and cocaine; corticosterone levels were lower in these adolescent animals, after exposure to the novel environment. These effects of maternal separation were not observed in rats that were tested as adults. Thus the maternal separation protocol produced enduring but transient changes in the behavioral response to cocaine and in the stress response to novelty. PMID:15196970

  2. Inactivation Or Inhibition Of Neuronal Activity In The Medial Prefrontal Cortex Largely Reduces Pup Retrieval And Grouping in Maternal Rats

    PubMed Central

    Febo, Marcelo; Felix-Ortiz, Ada C.; Johnson, Tehya R.

    2010-01-01

    Previous research suggests that the maternal medial prefrontal cortex (mPFC) may play a role in maternal care and that cocaine sensitization before pregnancy can affect neuronal activity within this region. The present work was carried out to test whether the mPFC does actually play a role in the expression of maternal behaviors in the rats and to understand what specific behaviors this cortical area may modulate. In the first experiment, tetrodotoxin (TTX) was used to chemically inactivate the mPFC during tests for maternal behavior latencies. Lactating rats were tested on postpartum day 79. The results of this first experiment indicate that there is a large effect of TTX-induced inactivation on retrieval behavior latencies. TTX nearly abolished the expression of maternal retrieval of pups without significantly impairing locomotor activity. In the second experiment, GABA-mediated inhibition was used to test maternal behavior latencies and durations of maternal and other behaviors in postpartum dams. In agreement with experiment 1, it was observed that dams capable of retrieving are rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the mPFC largely reduced retrieval without altering other indices of maternal care and non-specific behavior such as ambulation time, self-grooming, and inactivity. Moreover, in both experiments dams were able to establish contact with pups within seconds. The overall results indicate that the mPFC may play an active role in modulating maternal care, particularly retrieval behavior. External factors that affect the function of the frontal cortical site may result in significant impairments in maternal goal-directed behavior as reported in our earlier work. PMID:20156425

  3. Release of mercury from dental amalgam fillings in pregnant rats and distribution of mercury in maternal and fetal tissues.

    PubMed

    Takahashi, Y; Tsuruta, S; Hasegawa, J; Kameyama, Y; Yoshida, M

    2001-06-21

    Mercury vapor released from a single amalgam restoration in pregnant rats and mercury concentrations in maternal and fetal rat tissues were studied. Dental treatment was given on day 2 of pregnancy. Mercury concentration in air sample drawn from the metabolism chamber with the rat was measured serially for 24 h on days 2, 8 and 15 of pregnancy. An average mercury concentration in the air samples from the rats given amalgam restorations was 678.6+/-167.5 ng/day on day 2. The average mercury concentration in the air samples tended to decline as time elapsed but a marked amount (423.2+/-121.5 ng/day) was observed even on day 15. The amount of mercury in the air samples increased 7--20-fold after chewing. The placement of the single amalgam restoration (3.8--5.5 mg in weight) increased the levels of mercury approximately three to 6 times in the maternal brain, liver, lung, placenta and 20 times in the kidneys. The highest mercury concentration among fetal organs was found in the liver, followed by the kidneys and brain. Mercury concentrations in maternal organs and fetal liver were significantly higher than those of the controls, and concentrations in maternal whole blood, erythrocytes and plasma, and in fetal whole blood were also significantly higher. Mercury concentrations in the fetal brain, liver, kidneys and whole blood were lower than those of the maternal tissues. PMID:11516521

  4. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    PubMed Central

    Aires, M.B.; Santos, J.R.A.; Souza, K.S.; Farias, P.S.; Santos, A.C.V.; Fioretto, E.T.; Maria, D.A.

    2015-01-01

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers. PMID:26176314

  5. Increased affective ultrasonic communication during fear learning in adult male rats exposed to maternal immune activation.

    PubMed

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Whr, Markus

    2012-09-01

    Maternal exposure to infection during pregnancy greatly increases the risk of psychopathology in the offspring. In support of clinical findings, rodent models of maternal immune activation (MIA) show that prenatal exposure to pathogens can induce phenotypic changes in the offspring associated with schizophrenia, autism, depression and anxiety. In the current study, we investigated the effects of MIA via polyinosinic:polycytidylic acid (poly I:C) on emotional behavior and communication in rats. Pregnant rats were administered poly I:C or saline on gestation day 15 and male offspring were tested in an auditory fear conditioning paradigm in early adulthood. We found that prenatal poly I:C exposure significantly altered affective signaling, namely, the production of aversive 22-kHz ultrasonic vocalizations (USVs), in terms of call number, structure and temporal patterning. MIA led to an increase in aversive 22-kHz USVs to 300% of saline controls. Offspring exposed to MIA not only emitted more 22-kHz USVs, but also emitted calls that were shorter in duration and occurred in bouts containing more calls. The production of appetitive 50-kHz USVs and audible calls was not affected. Intriguingly, alterations in aversive 22-kHz USV emission were observed despite no obvious changes in overt defensive behavior, which highlights the importance of assessing USVs as an additional measure of fear. Aversive 22-kHz USVs are a prominent part of the rat's defensive behavioral repertoire and serve important communicative functions, most notably as alarm calls. The observed changes in aversive 22-kHz USVs show that MIA has long-term effects on emotional behavior and communication in exposed rat offspring. PMID:22687817

  6. Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy

    PubMed Central

    Lei, Fang; Yan, Xiang; Zhao, Fusheng; Zhang, Senfeng; Zhang, Qilan; Zhou, Hua; Zheng, Yu

    2015-01-01

    It has been postulated that prenatal cigarette smoke exposure (CSE) increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8) and CSE (n = 8). Experiments were performed on neonatal (0–3days) rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF) and integrated amplitude (IA) of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF) were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4), no significant difference was detected between the two groups in either BF or IA (P>0.05). Under condition of perfusing with acidified aCSF (pH 7.0), BF was increased and IA was decreased in both groups (P<0.01). However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and −22.38 ± 2.51% vs. −44.90 ± 3.92% for IA (P<0.01). In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates. PMID:26333001

  7. Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

    PubMed

    Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hrsten, Stephan; Stephan, Michael

    2014-02-01

    Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. PMID:24357522

  8. The stress of maternal separation causes misprogramming in the postnatal maturation of rat resistance arteries.

    PubMed

    Reho, John J; Fisher, Steven A

    2015-11-01

    We examined the effect of stress in the first 2 wk of life induced by brief periods of daily maternal separation on developmental programming of rat small resistance mesenteric arteries (MAs). In MAs of littermate controls, mRNAs encoding mediators of vasoconstriction, including the ?1a-adrenergic receptor, smooth muscle myosin heavy chain, and CPI-17, the inhibitory subunit of myosin phosphatase, increased from after birth through sexual [postnatal day (PND) 35] and full maturity, up to ?80-fold, as measured by quantitative PCR. This was commensurate with two- to fivefold increases in maximum force production to KCl depolarization, calcium, and the ?-adrenergic agonist phenylephrine, and increasing systolic blood pressure. Rats exposed to maternal separation stress as neonates had markedly accelerated trajectories of maturation of arterial contractile gene expression and function measured at PND14 or PND21 (weaning), 1 wk after the end of the stress protocol. This was suppressed by the ?-adrenergic receptor blocker terazosin (0.5 mgkg ip(-1)day(-1)), indicating dependence on stress activation of sympathetic signaling. Due to the continued maturation of MAs in control rats, by sexual maturity (PND35) and into adulthood, no differences were observed in arterial function or response to a second stressor in rats stressed as neonates. Thus early life stress misprograms resistance artery smooth muscle, increasing vasoconstrictor function and blood pressure. This effect wanes in later stages, suggesting plasticity during arterial maturation. Further studies are indicated to determine whether stress in different periods of arterial maturation may cause misprogramming persisting through maturity and the potential salutary effect of ?-adrenergic blockade in suppression of this response. PMID:26371173

  9. Neuroendocrine basis of thermally regulated maternal responses to young in the rat.

    PubMed

    Woodside, B; Jans, J E

    1988-01-01

    Over the first two weeks postpartum there is a decline in the amount of time that the rat dam spends with her young, resulting from a decrease in the duration of each nest bout. The duration of each nest bout is limited by the rate of rise of maternal temperature when she huddles with her litter. This pattern of mother-young contact is dependent on the dam's hormonal status, because adrenalectomised dams fail to show the expected decline in mother-young contact over time. Ovariectomy, on the other hand, does not have any effect on this behavior. Replacement therapy with glucocorticoids or placing the dam in a warm (25 degrees C) ambience reinstates the normal pattern of mother-litter contact in adrenalectomised-ovariectomised dams. These data suggest that the elevated level of serum glucocorticoids in lactating dams affects maternal behavior by increasing maternal heat load, thereby making the dam vulnerable to an acute rise in temperature when huddling with her young. Prolactin suppression also results in an increase in contact time between mother and young, but only in the second week postpartum. The effects of prolactin suppression are reversed by progesterone replacement or placing prolactin-suppressed females in a warm ambience. However, progesterone is ineffective in restoring the normal pattern of mother-litter contact in adrenalectomised females. These findings suggest that progesterone raises the thermal set point, thereby permitting the thermogenic effects of glucocorticoids to occur. PMID:3287419

  10. Adaptive significance of natural variations in maternal care in rats: a translational perspective

    PubMed Central

    Beery, Annaliese K.; Francis, Darlene D.

    2011-01-01

    A wealth of data from the last fifty years documents the potency of early life experiences including maternal care on developing offspring. A majority of this research has focused on the developing stress axis and stress-sensitive behaviors in hopes of identifying factors impacting resilience and risk-sensitivity. The power of early life experience to shape later development is profound and has the potential to increase fitness of individuals for their environments. Current findings in a rat maternal care paradigm highlight the complex and dynamic relation between early experiences and a variety of outcomes. In this review we propose adaptive hypotheses for alternate maternal strategies and resulting offspring phenotypes, and ways to distinguish between these hypotheses. We also provide evidence underscoring the critical role of context in interpreting the adaptive significance of early experiences. If our goal is to identify risk-factors relevant to humans, we must better explore the role of the social and physical environment in our basic animal models. PMID:21458485

  11. Functional mapping of the neural circuitry of rat maternal motivation: effects of site-specific transient neural inactivation

    PubMed Central

    Pereira, Mariana; Morrell, Joan I.

    2011-01-01

    The present review focuses on recent studies from our laboratory examining the neural circuitry subserving rat maternal motivation across postpartum. We employed a site-specific neural inactivation method by infusion of bupivacaine to map the maternal motivation circuitry using two complementary behavioral approaches: unconditioned maternal responsiveness and choice of pup- over cocaine-conditioned incentives in a concurrent pup/cocaine choice conditioned place preference task. Our findings revealed that during the early postpartum period, distinct brain structures, including the medial preoptic area, ventral tegmental area and medial prefrontal cortex infralimbic and anterior cingulate subregions, contribute a pup-specific bias to the motivational circuitry. As the postpartum period progresses and the pups grow older, our findings further revealed that maternal responsiveness becomes progressively less dependent on medial preoptic area and medial prefrontal cortex infralimbic activity, and more distributed in the maternal circuitry, such that additional network components, including the medial prefrontal cortex prelimbic subregion, are recruited with maternal experience, and contribute to the expression of late postpartum maternal behavior. Collectively, our findings provide strong evidence that the remarkable ability of postpartum females to successfully care for their developing infants is subserved by a distributed neural network that carries out efficient and dynamic processing of complex, constantly changing incoming environmental and pup-related stimuli, ultimately allowing the progression of appropriate expression and waning of maternal responsiveness across the postpartum period. PMID:21815954

  12. Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids-fetal effect or maternal influence?

    PubMed

    Nyirenda, M J; Welberg, L A; Seckl, J R

    2001-09-01

    In a previous study, we showed that exposure of rats to dexamethasone (Dex) selectively in late pregnancy produces permanent induction of hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression and hyperglycaemia in the adult offspring. The mechanisms by which glucocorticoids cause this programming are unclear but may involve direct actions on the fetus/neonate, or glucocorticoids may act indirectly by affecting maternal postnatal nursing behaviour. Using a cross-fostering paradigm, the present data demonstrate that switching the offspring at birth from Dex-treated dams to control dams does not prevent induction of PEPCK or hyperglycaemia. Similarly, offspring born to control dams but reared by Dex-treated dams from birth maintain normal glycaemic control. During the neonatal period, injection of saline per se was sufficient to cause exaggeration in adult offspring responses to an oral glucose load, with no additional effect from Dex. However, postnatal treatment with either saline or Dex did not alter hepatic PEPCK activity. Prenatal Dex permanently raised basal plasma corticosterone levels, but under stress conditions there were no differences in circulating corticosterone levels. Likewise, Dex-exposed rats had similar plasma catecholamine concentrations to control animals. These findings show that glucocorticoids programme hyperglycaemia through mechanisms that operate on the fetus or directly on the neonate, rather than via effects that alter maternal postnatal behaviour during the suckling period. The hyperglycaemic response does not appear to result from abnormal sympathoadrenal activity or hypothalamic-pituitary-adrenal response during stress. PMID:11524246

  13. Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

    PubMed

    Pérez-Laso, Carmen; Segovia, Santiago; Martín, José Luis R; Ortega, Esperanza; Gómez, Francisco; Del Cerro, M Cruz R

    2008-03-01

    The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity. PMID:17980921

  14. Early maternal deprivation-induced modifications in the neurobiological, neurochemical and behavioral profile of adult rats.

    PubMed

    Rentesi, Georgia; Antoniou, Katerina; Marselos, Marios; Syrrou, Marika; Papadopoulou-Daifoti, Zeta; Konstandi, Maria

    2013-05-01

    Early maternal deprivation (MD) is an animal model of neurodevelopmental stress associated with a variety of abnormalities during adulthood. The present study investigated specific behavioral, neurochemical and neurobiological parameters related to dopaminergic and serotonergic function in adult rats subjected to early life MD. Behavioral responses, including the reaction to novelty, the response to d-amphetamine (d-AMP) and the susceptibility to apomorphine (APO) were evaluated in adulthood. Dopamine (DA) and serotonin (5-HT) levels, their metabolites along with their turnover ratios were assessed in distinct rat brain regions. The impact of MD on DARPP-32 protein, D2 and 5-HT2A receptor expression was also estimated in the same brain regions during adulthood. Our results indicated that MD rats were more reactive to novelty behavior and more sensitive to dopaminergic agonists compared to controls. MD rats displayed elevated dopaminergic and serotonergic function in the amygdala and prefrontal cortex, whereas in the striatum only the dopaminergic activity was also increased. Interestingly, MD induced a region-dependent modulation of D2, 5-HT2A receptor and DARPP-32 protein expression. Our findings clearly indicated that early MD stress produces long term behavioral impairments and region-dependent modifications in various neurochemical and neurobiological indices of dopaminergic and serotonergic function in brain regions holding critical roles in the pathophysiology of central nervous system disorders. PMID:23395600

  15. Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats

    PubMed Central

    Ferreira, Vanessa Meira; Passos, Clevia Santos; Maquigussa, Edgar; Pontes, Roberto Braz; Bergamaschi, Cassia Toledo; Campos, Ruy Ribeiro; Boim, Mirian Aparecida

    2016-01-01

    Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg-1·day-1) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy. PMID:26914675

  16. Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.

    PubMed

    Ferreira, Vanessa Meira; Passos, Clevia Santos; Maquigussa, Edgar; Pontes, Roberto Braz; Bergamaschi, Cassia Toledo; Campos, Ruy Ribeiro; Boim, Mirian Aparecida

    2016-01-01

    Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg-1·day-1) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy. PMID:26914675

  17. Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

    PubMed Central

    Jones, Megan L.; Mark, Peter J.; Keelan, Jeffrey A.; Barden, Anne; Mas, Emilie; Mori, Trevor A.; Waddell, Brendan J.

    2013-01-01

    Placental inflammation is associated with several pregnancy disorders. Inflammation is limited by anti-inflammatory and proresolving mechanisms, the latter partly mediated by resolvins and protectins derived from omega-3 polyunsaturated fatty acids (n-3PUFA). We examined effects of dietary n-3PUFAs on levels of resolvins, protectins, and lipoxygenase (ALOX) enzymes in the rat placenta. Rats consumed standard (Std) or high n-3PUFA (Hn3) diets from day 1 of pregnancy; tissues were collected on day 17 or 22 (term = day 23). Maternal Hn3 diet increased resolvin and protectin precursors, 18R/S-HEPE (P < 0.001), and 17R/S-HDHA (P < 0.01) at both days. Resolvins (17R-RvD1 and RvD1) increased at day 22 (P < 0.001) after Hn3 consumption, coincident with higher Alox15b and Alox5 mRNA expression, while RvD2 increased at both days (P < 0.05). Protectins, PD1, and 10S,17S-DiHDHA increased over late gestation (P < 0.001), coincident with higher Alox15 mRNA expression (P < 0.001) and further increased with Hn3 diet (P < 0.05). Maternal systemic and placental proinflammatory mediators were not suppressed by Hn3 diet; systemic IL1?, placental Il1?, and Il6 mRNA expression increased marginally with Hn3 at day 22 (P < 0.001), while Ptgs1 (Cox1) expression increased both days (P < 0.05). Our data indicate that maternal n-3PUFA supplementation enhances expression of enzymes in the n-3PUFA metabolic pathway and increases placental levels of resolvins and protectins. PMID:23723388

  18. The effect of maternal alcohol consumption on the viability and visceral development of the newborn rat.

    PubMed

    Henderson, G I; Schenker, S

    1977-01-01

    The clinical observations that offspring of pregnant alcoholics are prone to congenital defects and abnormal growth and development (fetal alcohol syndrome) have generated interest in studying this problem in a well-controlled experimental model. Accordingly, in this study, we assessed the effects of long-term maternal alcohol intake on offspring viability and growth as well as the DNA, total RNA, protein levels and DNA synthesis in brain, heart, liver, and kidney of 3-day-old newborn rats. Chronic oral intake of alcohol (mean 21 weeks plus 20 days of gestation) resulted in maternal blood alcohol levels of 67 to over 150 mg percent. There was a significant increase of newborn mortality (30%) and a decrease in their body weight at 3 days in alcohol-exposed compared to pair-fed (non-alcohol) control pups (p less than 0.025). Protein concentration was unchanged in heart, liver, and kidney and was slightly elevated in brain of 3-day-old pups exposed to ethanol in utero. DNA synthesis rates were normal in all four organs, while DNA concentration was significantly lower only in the liver of the alcohol-exposed group (p less than 0.05). In the alcohol group the total RNA levels were significantly depressed by about 10-30 percent (p less than 0.05) in all four organs studied. In conclusion, our studies suggest that prolonged maternal alcohol intake has an adverse effect on newborn rat viability and growth as well as the total RNA and to some extent DNA concentration of vital organs. PMID:841175

  19. Effect of maternal exercise on biochemical parameters in rats submitted to neonatal hypoxia-ischemia.

    PubMed

    Marcelino, Thiago Beltram; de Lemos Rodrigues, Patrcia Idalina; Miguel, Patrcia Maidana; Netto, Carlos Alexandre; Pereira Silva, Lenir Orlandi; Matt, Cristiane

    2015-10-01

    Pregnancy is a critical period for brain metabolic programming, being affected by individual environment, such as nutrition, stress, and physical exercise. In this context, we previously reported a cerebral antioxidant upregulation and mitochondrial biogenesis in the offspring delivered from exercised mothers, which could provide neuroprotection against neonatal insults. Hypoxia-ischemia (HI) encephalopathy is one of the most studied models of neonatal brain injury; disrupting motor, cognitive, and learning abilities. Physiopathology includes oxidative stress, allied to mitochondria energy production failure, glutamatergic excitotoxicity, and cell death. In this study we evaluated the effect of maternal swimming during pregnancy on offspring?s brain oxidative status evaluated fourteen days after HI stablishment. Swimming exercise was performed by female adult rats one week before and during pregnancy, in controlled environment. Their offspring was submitted to HI on postnatal day 7, and the brain samples for biochemical assays were obtained in the weaning. Contrary to our expectations, maternal exercise did not prevent the oxidative alterations observed in brain from HI-rats. In a general way, we found a positive modulation in the activities of antioxidant enzymes, measured two weeks after HI, in hippocampus, striatum, and cerebellum of pups delivered from exercised mothers. Reactive species levels were modulated differently in each structure evaluated. Considering the scenery presented, we concluded that HI elicited a neurometabolic adaptation in both brain hemispheres, particularly in hippocampus, parietal cortex, and cerebellum; while striatum appears to be most damaged. The protocol of aerobic maternal exercise was not enough to fully prevent HI-induced brain damages. PMID:26119914

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

    PubMed

    Sandini, Thasa M; Udo, Mariana S B; Reis-Silva, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice de S

    2014-08-01

    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 9 mg/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. PMID:24881561

  1. Treadmill exercise during pregnancy ameliorates post?traumatic stress disorder?induced anxiety?like responses in maternal rats.

    PubMed

    Seo, Jin-Hee; Kim, Tae-Woon; Kim, Chang-Ju; Sung, Yun-Hee; Lee, Sam-Jun

    2013-02-01

    Post?traumatic stress disorder (PTSD) is an anxiety disorder triggered by life?threatening events that cause intense fear. Exercise is known to have protective effects on neuropsychiatric diseases. The present study investigated whether treadmill exercise during pregnancy reduced or alleviated symptoms of PTSD in maternal rats. To induce predator stress in pregnant rats, rats were exposed to a hunting dog in an enclosed room. Exposure time was three 10?min daily sessions separated by 1 h, starting at week 1 of pregnancy until delivery. Pregnant rats in the exercise group were forced to run on a treadmill for 30 min once a day, starting one week following pregnancy until delivery. Rats receiving predator stress during pregnancy exhibited PTSD anxiety?like behaviors following delivery. Expression of 5?hydroxytryptamine (5?HT) and its synthesizing enzyme tryptophan hydroxylase (TPH) in the dorsal raphe was increased compared with unstressed rats. Expression of c?Fos and neuronal nitric oxide synthases (nNOS) in the hypothalamus and locus coeruleus were higher in the rats receiving stress during pregnancy compared with unstressed rats. By contrast, treadmill exercise during pregnancy ameliorated anxiety?like behaviors and reduced the expression of 5?HT, TPH, c?Fos and nNOS in the PTSD maternal rats. The results of the present study indicate that exercise during pregnancy is suitable for use as a therapeutic strategy to reduce anxiety?related disorders, including PTSD. PMID:23174863

  2. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

    PubMed

    Vessires, Emilie; Dib, Abdallah; Bourreau, Jennifer; Lelivre, Eric; Custaud, Marc-Antoine; Lelivre-Pgorier, Martine; Loufrani, Laurent; Henrion, Daniel; Fassot, Cline

    2016-01-01

    Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside) relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life. PMID:26756337

  3. Maternal Separation Enhances Neuronal Activation and Cardiovascular Responses to Acute Stress in Borderline Hypertensive Rats

    PubMed Central

    Sanders, Brian J.; Anticevic, Alan

    2007-01-01

    There is much evidence suggesting early life events, such has handling or repeated separations from the nest, can have a long term effect on the biological and behavioral development of rats. The current study examined the effect of repeated maternal separation (MS) on the behavioral, cardiovascular, and neurobiological responses to stress in subjects vulnerable to environmental stressors as adults. Borderline hypertensive rats (BHR), which are the first generation offspring of spontaneously hyperternsive and Wistar-Kyoto rats, were separated from the dams for 3 hours per day from post-natal day 1 through 14. Non-separated controls remained in the home cage. When allowed to explore the open field chamber for 60 minutes as adults, MS subjects had significantly greater locomotor activity compared to controls. All subjects were exposed to 30 minutes of restraint stress during which time mean arterial pressure (MAP) and heart rate (HR) were measured. Although both groups had comparable increases in MAP, MS animals displayed significantly higher HR throughout the stress period. Finally, MS subjects had significantly more stress-induced Fos positive cells, an estimate of neuronal activation, in the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and the bed nucleus of the stria terminalis (BNST), each of which plays an important role in organizing the biobehavioral response to stress. These results suggest that maternal separation can further enhance stress reactivity in this model and may represent a useful approach for studying the relationship between early life events and future vulnerability to stressful situations. PMID:17604851

  4. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia

    PubMed Central

    Vessières, Emilie; Dib, Abdallah; Bourreau, Jennifer; Lelièvre, Eric; Custaud, Marc-Antoine; Lelièvre-Pégorier, Martine; Loufrani, Laurent; Henrion, Daniel; Fassot, Céline

    2016-01-01

    Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside) relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life. PMID:26756337

  5. Exercise partially reverses the effect of maternal separation on hippocampal proteins in 6-hydroxydopamine lesioned rat brain

    PubMed Central

    Dimatelis, JJ; Hendricks, S; Hsieh, J; Vlok, NM; Bugarith, K; Daniels, WMU; Russell, VA

    2012-01-01

    Animals subjected to maternal separation stress during the early stages of development display behavioural, endocrine and growth factor abnormalities that mirror the clinical findings in anxiety/depression. In addition, maternal separation has been shown to exacerbate the behavioural deficits induced by 6-hydroxydopamine (6-OHDA) in a rat model of Parkinson's disease. In contrast, voluntary exercise reduced the detrimental effects of 6-OHDA in the rat model. The beneficial effects of exercise appeared to be largely due to compensation in the non-lesioned hemisphere. The aim of the present study was to investigate whether voluntary exercise for 3 weeks could reverse the effects of maternal separation in rats challenged with the neurotoxin 6-OHDA infused into the medial forebrain bundle after 1 week of exercise, at postnatal day 60 (P60). The rats were killed 2 weeks later, at P74. Their brains were dissected and the hippocampus rapidly removed for proteomic analysis - isobaric tagging (iTRAQ) and quantification of peptides by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS). Maternal separation up-regulated hippocampal proteins functionally involved in energy metabolism (nucleoside diphosphate kinase B, enolase, triosephosphate isomerase) and synaptic plasticity (alpha-synuclein, tenascin-R, Ba1-667, brevican and neurocan core protein) in the non-lesioned hemisphere. Exercise reversed many of these changes by down-regulating the levels of hippocampal proteins functionally associated with energy metabolism (nucleoside diphosphate kinase B, enolase, triosephosphate isomerase) and synaptic plasticity (alpha-synuclein, tenascin-R, Ba1-667, brevican and neurocan core protein) in the non-lesioned hemisphere of rats subjected to maternal separation. Exercise and maternal separation therefore appeared to have opposing effects on the hippocampus in the non-lesioned hemisphere of the rat brain. Exercise seemed to partially reverse the effects of maternal separation stress on these proteins in the non-lesioned hemisphere. The partial reversal of maternal separation-induced proteins by exercise in the non-lesioned side sheds some insight into the mechanism by which exercise alters the molecular role players involved in determining the consequences of early life stress. PMID:22636255

  6. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

    PubMed

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-07-15

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-? mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. PMID:25922055

  7. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In utero exposure to maternal obesity increases the offspring’s risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND) 21. In the current s...

  8. Female rats are resistant to developing the depressive phenotype induced by maternal separation stress.

    PubMed

    Dimatelis, J J; Vermeulen, I M; Bugarith, K; Stein, D J; Russell, V A

    2016-02-01

    Many stress-related psychiatric disorders are more common in women than in men. We aimed to determine how female rats respond to maternal separation (MS; removal of the dam from the litter for 3h/day from postnatal day (P) 2-14)). A subset of MS females were also exposed to chronic constant light for 3weeks during adolescence (P42-63) to investigate whether the antidepressant effect of light treatment, previously observed in male rats, could be seen in female rats. Ultrasonic vocalizations (22kHz) were recorded and the forced swim test was conducted immediately after light exposure (P65-67) and 33days later (P98-99) to determine depressive-like behaviour. Key proteins in the MAPK signal transduction pathway (MKP-1, phospho-ERK, total ERK) and a synaptosomal marker (synaptophysin) were measured in the ventral hippocampus. We found that MS decreased the duration of 22kHz vocalizations at P65 which was reversed by subsequent light. Light exposure increased time spent in the inner zone of the open field and the number of 22kHz calls in response to novelty at P98. MS decreased the time females spent immobile and increased time actively swimming in the forced swim test at P67 but not at P99. MKP-1 and synaptophysin levels remained unchanged while MS decreased phospho-ERK levels in the ventral hippocampus. In contrast to clinical findings, the results suggest that female rats may be resistant to MS-induced depression-like behaviour. The behavioural effects of MS and light treatment in female rats may involve the MAPK/ERK signal transduction pathway. PMID:26344502

  9. Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

    PubMed Central

    Elmes, Matthew; Szyszka, Alexandra; Pauliat, Caroline; Clifford, Bethan; Daniel, Zoe; Cheng, Zhangrui; Wathes, Claire; McMullen, Sarah

    2015-01-01

    Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways. PMID:25876907

  10. Stress-Induced Visceral Hypersensitivity in Maternally Separated Rats Can Be Reversed by Peripherally Restricted Histamine-1-Receptor Antagonists

    PubMed Central

    Stanisor, Oana I.; van Diest, Sophie A.; Yu, Zhumei; Welting, Olaf; Bekkali, Noor; Shi, Jing; de Jonge, Wouter J.; Boeckxstaens, Guy E.; van den Wijngaard, Rene M.

    2013-01-01

    Background The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats. Methods The visceromotor response to colonic distension was assessed in adult maternally separated and nonhandled rats pre- and 24 hours post water avoidance. Subsequently rats were treated with vehicle alone or different dosages of fexofenadine (1.8 and 18 mg/kg) or ebastine (0.1 and 1.0 mg/kg) and re-evaluated. Colonic tissue was collected to assess relative RMCP-2 and occludin expression levels by Western blot and histamine-1 receptor by RT-qPCR. β-hexosaminidase release by RBL-2H3 cells was used to establish possible mast cell stabilizing properties of the antagonists. Key results Water avoidance only induced enhanced response to distension in maternally separated rats. This response was reversed by 1.8 and 18 mg/kg fexofenadine. Reversal was also obtained by 1.0 but not 0.1 mg/kg ebastine. RMCP-2 expression levels were comparable in these two ebastine treatment groups but occludin was significantly higher in 1.0 mg/kg treated rats. There were no differences in histamine-1 receptor expression between nonhandled and maternally separated rats. Fexofenadine but not ebastine showed mast cell stabilizing quality. Conclusions Our results indicate that the peripherally restricted 2nd generation H1-receptor antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rat. These data justify future IBS patient trials with these well tolerated compounds. PMID:23776699

  11. Maternal attenuation of hypothalamic paraventricular nucleus norepinephrine switches avoidance learning to preference learning in preweanling rat pups

    PubMed Central

    Shionoya, Kiseko; Moriceau, Stephanie; Bradstock, Peter; Sullivan, Regina M.

    2009-01-01

    Infant rats learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver to receive protection and food. With maturity, a more adult-like learning system emerges that includes the amygdala and avoidance/fear learning. The attachment and adult-like systems appear to co-exist in older pups with maternal presence engaging the attachment system by lowering corticosterone (CORT). Specifically, odor-shock conditioning (11 odor-0.5mA shock trials) in 12-day old pups results in an odor aversion, although an odor preference is learned if the mother is present during conditioning. Here, we propose a mechanism to explain pups ability to switch between the dual learning systems by exploring the effect of maternal presence on hypothalamic paraventricular nucleus (PVN) neural activity, norepinephrine (NE) levels and learning. Maternal presence attenuates both PVN neural activity and PVN NE levels during odor-shock conditioning. Intra-PVN NE receptor antagonist infusion blocked the odor aversion learning with maternal absence, while intra-PVN NE receptor agonist infusion permitted odor aversion learning with maternal presence. These data suggest maternal control over pup learning acts through attenuation of PVN NE to reduce the CORT required for pup odor aversion learning. Moreover, these data also represent pups continued maternal dependence for nursing, while enabling aversion learning outside the nest to prepare for pups future independent living. PMID:17675020

  12. Maternal metallothionein and zinc after acute ethanol exposure during gestation in the rat

    SciTech Connect

    Harris, J.E. )

    1992-02-26

    Acute exposure of the rat fetus to ethanol at critical periods can cause growth retardation and brain damage; the mechanism(s) is not known. Ethanol may cause redistribution of maternal zinc which results in fetal zinc deficiency and subsequent interruption of growth and development. The purpose was to determine if acute ethanol administration to the pregnant rat alters Zn and the Zn binding protein metallothionein (MT) in selected tissues. On gestational day (gd) 14, eighteen pregnant Sprague-Dawley rats were divided into groups. By intragastric tube, ethanol treated dams were given ethanol and pairfed controls were given a 0.85% NaCl solution. On gd 15, intragastric feedings were repeated. Throughout, the Lieber-DeCarli control diet was fed (adlibitum to untreated controls and ethanol treated dams and in appropriate quantities to pair fed controls). Blood ethanol concentrations at 90 minutes after the ethanol dose were 154 {plus minus} 46 and 265 {plus minus} 110 mg% on gd 14 and 15, respectively.

  13. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    PubMed

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. PMID:26592720

  14. Oxidative Stress in Maternal Blood and Placenta From Mild Diabetic Rats

    PubMed Central

    Spada, Ana Paula Machado; Sinzato, Yuri Karen; Campos, Kleber Eduardo; Faria, Priscila Afonso; Dallaqua, Bruna; Calderon, Iracema Mattos Paranhos; Rudge, Marilza Vieira Cunha; Rodrigues, Tiago

    2014-01-01

    The aim of the present study was at evaluating the effects of oxidative stress in blood and placenta of mild diabetic Wistar rats. At birth, Wistar rats received citrate buffer (nondiabetic group, n = 15) and another group received streptozotocin (100 mg/kg, subcutaneous) to induce mild diabetes (diabetic, n = 15). The glycemia of these pregnant adult female rats were evaluated at days 0, 7, 14, and 21 of pregnancy, and at term pregnancy, the blood and placental samples were collected for oxidative stress measurements. The mild diabetes caused glycemia superior to 120 mg/dL during pregnancy, increased superoxide dismutase, glutathione peroxidase, glutathione reductase activities, and malondialdehyde levels in the blood, and catalase activity in the placenta. Thus, mild diabetes increased activities of antioxidant substances aiming at defending against the exacerbated oxidative stress but were not enough. The placenta also answered to diabetic milieu and increased antioxidant defense, showing that even a mild hyperglycemia was enough to cause placental and maternal blood changes. PMID:24458484

  15. Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature.

    PubMed

    Shifrin, Yulia; Sadeghi, Sina; Pan, Jingyi; Jain, Amish; Fajardo, Andres F; McNamara, Patrick J; Belik, Jaques

    2015-11-15

    The factors accounting for the pathological maintenance of a high pulmonary vascular (PV) resistance postnatally remain elusive, but neonatal stressors may play a role in this process. Cross-fostering in the immediate neonatal period is associated with adult-onset vascular and behavioral changes, likely triggered by early-in-life stressors. In hypothesizing that fostering newborn rats induces long-lasting PV changes, we evaluated them at 14 days of age during adulthood and compared the findings with animals raised by their biological mothers. Fostering resulted in reduced maternal-pup contact time when compared with control newborns. At 2 wk of age, fostered rats exhibited reduced pulmonary arterial endothelium-dependent relaxation secondary to downregulation of tissue endothelial nitric oxide synthase expression and tetrahydrobiopterin deficiency-induced uncoupling. These changes were associated with neonatal onset-increased ANG II receptor type 1 expression, PV remodeling, and right ventricular hypertrophy that persisted into adulthood. The pulmonary arteries of adult-fostered rats exhibited a higher contraction dose response to ANG II and thromboxane A2, the latter of which was abrogated by the oxidant scavenger Tempol. In conclusion, fostering-induced neonatal stress induces long-standing PV changes modulated via the renin-angiotensin system. PMID:26342088

  16. Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats

    PubMed Central

    Paternain, Laura; Martisova, Eva; Milagro, Fermín I.; Ramírez, María J.; Martínez, J. Alfredo; Campión, Javier

    2012-01-01

    SUMMARY An early-life adverse environment has been implicated in the susceptibility to different diseases in adulthood, such as mental disorders, diabetes and obesity. We analyzed the effects of a high-fat sucrose (HFS) diet for 35 days in adult female rats that had experienced 180 minutes daily of maternal separation (MS) during lactancy. Changes in the obesity phenotype, biochemical profile, levels of glucocorticoid metabolism biomarkers, and the expression of different obesity- and glucocorticoid-metabolism-related genes were analyzed in periovaric adipose tissue. HFS intake increased body weight, adiposity and serum leptin levels, whereas MS decreased fat pad masses but only in rats fed an HFS diet. MS reduced insulin resistance markers but only in chow-fed rats. Corticosterone and estradiol serum levels did not change in this experimental model. A multiple gene expression analysis revealed that the expression of adiponutrin (Adpn) was increased owing to MS, and an interaction between HFS diet intake and MS was observed in the mRNA levels of leptin (Lep) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). These results revealed that early-life stress affects the response to an HFS diet later in life, and that this response can lead to phenotype and transcriptomic changes. PMID:22773756

  17. Influence of maternal ethanol ingestion on copper utilization during gestation and lactation in the rat

    SciTech Connect

    Baek, J.H.; Cerklewski, F.L.

    1986-03-05

    A factorial experiment was conducted to determine the influence of ethanol intake (30% of Kcal) on the utilization of copper (Cu) at two dietary levels of Cu during gestation and lactation in the rat. Cu levels in the liquid diet were adjusted to provide either 60% of the minimum requirement or a more than adequate intake. Both ethanol and low Cu depressed dam liver Cu, but the lowest concentration was produced when ethanol and low Cu were combined. Although only ethanol depressed pup liver Cu concentration, the effects observed in dams were reflected in pup Cu content of the metallothionein fraction eluted from a Sephadex G-75 column. Otherwise, neither the metallothionein content of maternal intestinal cells nor that of pup liver affected the outcome of ethanol-antagonized Cu utilization. Effects of ethanol on Cu status of dams and pups cannot be defined as a simple C deficiency even though liver iron was elevated because the ferroxidase activity of dam ceruloplasmin was enhanced rather than inhibited by ethanol which is in agreement with observations made in alcoholics. The authors results are more consistent with a possible enhancing effect of ethanol on biliary excretion of Cu. Exactly why ethanol would have this effect in dams is not defined by available data. In pups, however, maternal ethanol ingestion caused a 30% increase in pup plasma corticosterone, a steroid known to enhance loss of neonatal liver Cu by way of biliary excretion.

  18. Maternal behavior: activation of the central oxytocin receptor system in parturient rats?

    PubMed

    Lin, Shi Hua; Kiyohara, Toshikazu; Sun, Bing

    2003-08-01

    Parturition plays a critical role in the full expression of maternal behavior in postpartum females, yet the precise mechanism remains unclear. Here we examined the role of parturition in the activation of Fos and FosB in the central oxytocin receptor (OTR) system in rats. Although expression of FosB, not Fos, was seen in the piriform cortex (Pir) and caudate putamen of virgin and pregnant females, activation of Fos and FosB with extensive co-localization was found in the medial preoptic area, the bed nucleus of the stria terminalis and Pir of parturient brain. This parturition induced activation of Fos and FosB was identified in the central OTR-expressing cells as well as in oxytocinergic neurons. Our data provide direct evidence, for the first time, that parturition activates Fos and FosB in the central OTR system. We propose that Fos and FosB may have comparable functions on initiating maternal behavior at parturition. PMID:12960760

  19. Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

    PubMed Central

    Gordon, Erin E.; Reinking, Benjamin E.; Hu, Shanming; Yao, Jianrong; Kua, Kok L.; Younes, Areej K.; Wang, Chunlin; Segar, Jeffrey L.; Norris, Andrew W.

    2015-01-01

    Cardiac septal overgrowth complicates 10–40% of births from diabetic mothers, but perplexingly hyperglycemia markers during pregnancy are not reliably predictive. We thus tested whether fetal exposure to hyperglycemia is sufficient to induce fetal cardiac septal overgrowth even in the absence of systemic maternal diabetes. To isolate the effects of hyperglycemia, we infused glucose into the blood supply of the left but not right uterine horn in nondiabetic pregnant rats starting on gestational day 19. After 24 h infusion, right-sided fetuses and dams remained euglycemic while left-sided fetuses were moderately hyperglycemic. Echocardiograms in utero demonstrated a thickened cardiac septum among left-sided (glucose-exposed, 0.592 ± 0.016 mm) compared to right-sided (control, 0.482 ± 0.016 mm) fetuses. Myocardial proliferation was increased 1.5 ± 0.2-fold among left-sided compared to right-sided fetuses. Transcriptional markers of glucose-derived anabolism were not different between sides. However, left-sided fetuses exhibited higher serum insulin and greater JNK phosphorylation compared to controls. These results show that hyperglycemic exposure is sufficient to rapidly induce septal overgrowth even in the absence of the myriad other factors of maternal diabetes. This suggests that even transient spikes in glucose may incite cardiac overgrowth, perhaps explaining the poor clinical correlation of septal hypertrophy with chronic hyperglycemia. PMID:26064981

  20. Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

    PubMed

    Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

    2015-09-01

    Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. PMID:25982389

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

    PubMed Central

    2010-01-01

    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. PMID:20529353

  2. Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain.

    PubMed

    Boksa, Patricia; Zhang, Ying; Nouel, Dominique

    2015-08-01

    Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth. PMID:26108713

  3. Behavioral and pharmacological investigation of anxiety and maternal responsiveness of postpartum female rats in a pup elevated plus maze.

    PubMed

    Yang, Yu; Qin, Jingxue; Chen, Weihai; Sui, Nan; Chen, Hong; Li, Ming

    2015-10-01

    The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague-Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more than nulliparous rats. They also tended to spend more time in the open arms, indicating reduced anxiety. When tested with pups, postpartum rats retrieved pups into the closed arms, entered the open arms and closed arms more and had a higher moving speed than nulliparous rats, indicating increased maternal responsiveness. Both haloperidol (0.1 or 0.2 mg/kg, sc) and fluoxetine (5 or 10 mg/kg, ip) dose- and time-dependently decreased the percentage of time spent in the open arms and speed, but did not affect the percentage of open arm entries. Diazepam (1.0 or 2.0 mg/kg, ip) did not affect pup retrieval, open arm time/entry in lactating rats. Thus, the percentage of open arm entries appears to be the most sensitive measure of anxiety in postpartum female rats, while speed could be used to index maternal responsiveness to pups, which are likely mediated by the dopamine D2 and serotonin transporter systems. PMID:26159828

  4. Influence of maternal cadmium exposure or fetal cadmium injection on hepatic metallothionein concentrations in the fetal rat

    SciTech Connect

    Sasser, L.B.; Kelman, B.J.; Levin, A.A.; Miller, R.K.

    1985-01-01

    The ability of Cd to induce the synthesis of fetal hepatic metallothionein (MT) was investigated in rat fetuses exposed to Cd throughout gestation via the mother's drinking water or injected directly with Cd through the uterine wall on Day 18 of gestation. On Day 21 all dams were killed and fetal and maternal tissues were removed. Tissue MT, Zn, Cu, and Cd concentrations were measured. Fetal hepatic Cd concentration was increased only at the high maternal Cd exposure, whereas Zn concentration was significantly reduced by Cd exposure. Both fetal liver and kidney MT were reduced following maternal Cd exposure. Unlike maternal hepatic MT, fetal hepatic MT was not increased after maternal Cd exposure nor did the direct injection of Cd into the 18 days of gestation fetus induce fetal MT synthesis. These data suggest that fetal rat liver is incapable of synthesizing MT in response to Cd, possibly because Cd is not transported to the site of MT synthesis in the fetal system. Furthermore, neither the route of exposure, the duration of prenatal Cd exposure, nor the stage of gestation appear to account for the differences observed between fetal and adult hepatic MT induction by Cd. 47 references, 6 tables.

  5. Effects of Maternal Caffeine Consumption on Ovarian Follicle Development in Wistar Rats Offspring

    PubMed Central

    Dorostghoal, Mehran; Mahabadi, Mahmood Khaksari; Adham, Sahar

    2011-01-01

    Background In recent years concerns have been raised about human reproductive disorders, specially the effects of environmental factors on human fertility and pregnancy outcome. Therefore, the present study was designed to assess the effects of maternal caffeine consumption on ovarian follicles development in rat offspring. Methods 60 pregnant female rats were randomly divided into a control and two experimental groups. The rats in the two experimental groups received caffeine via drinking water during gestation (26 and 45 mg/kg) and lactation (25 and 35 mg/kg). The ovaries of the offspring were removed at 7, 14, 28, 60, 90 and 120 days after birth, and fixed in Bouin's solution. By preparing serial tissue sections, structural changes in ovarian follicles and corpora lutea were studied during postnatal development. Results The weight of ovaries decreased significantly (p<0.05) in the high dose caffeine-treated group at all stages of postnatal development. Significant (p<0.05) decreases were seen in the number of primordial follicles from day 7 to 120 after birth in the high dose caffeine-treated group. Moreover, the number of primary and secondary follicles decreased significantly on days 7, 14 and 28 as did the number of antral follicles on days 14 and 28 after birth (p<0.05) in the high dose caffeine-treated group. The diameter of secondary and antral follicles decreased significantly (p<0.05) in high dose caffeine-treated group on the early days of postnatal development. No statistically significant differences were seen in the number of corpora lutea between the groups. Conclusion The present study shows that caffeine consumption during gestation and lactation affects the early stages of ovarian follicle development and reduces reproductive efficiency in the offspring of Wistar rats. PMID:23926495

  6. Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat

    PubMed Central

    2014-01-01

    Background There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels. Methods We intravenously injected monodisperse, negatively charged, radio-labelled 1.4nm, 18nm and 80nm 198AuNP at a mass dose of 5, 3 and 27?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled 198AuNP after 24hours. Results We observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of 198AuNP were found in the placentas and amniotic fluids with 1.4nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30ng) and 0.00004 (0.1ng) of 1.4nm and 18nm AuNP, respectively, were detected, but no 80nm AuNP (<0.000004 (<0.1ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes. Conclusion Our data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels also present in the human placenta and/or (2) endocytotic and diffusive processes across the placental barrier. PMID:25928666

  7. Effects of Maternal Dietary Restriction of Vitamin B-6 on Neocortex Development in Rats

    NASA Astrophysics Data System (ADS)

    Groziak, Susan Marie

    The aim of this investigation was to quantitate the effects of a dietary restriction in Vitamin B-6 during gestation or gestation and lactation on neurogenesis, neuron longevity and neuron differentiation in the neocortex of rats. Sprague Dawley female rats were fed, ad libitum, a Vitamin B-6 free diet (AIN 76) supplemented with 0.0 or 0.6 mg pyridoxine (PN)/kg diet during gestation followed by a control level of 7.0 mg PN/kg diet during lactation, or were fed the Vitamin B-6 free diet supplemented with 0.6 or 7.0 mg PN/kg diet throughout gestation and lactation. The neocortex of progeny of these animals were examined at 30 days of age employing light and electron microscopy. Analyses of neurogenesis, neuron longevity and differentiation of neurons (size of somata, dendritic arborization and spine density in Golgi Cox preparations, and synaptic density in E.M. preparations) were conducted. Each of the Vitamin B-6 restricted treatments adversely affected neurogenesis, neuron longevity and neuron differentiation. The degree of adverse effects paralleled the severity (dose or duration) of the restriction imposed. Expressed as percentage reduction from control values, the findings indicated that neuron longevity and differentiation of neurons in the neocortex were more severely affected than neurogenesis by a maternal dietary restriction in Vitamin B-6.

  8. Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.

    PubMed

    Xiong, Gui-Jing; Yang, Yuan; Wang, Li-Ping; Xu, Lin; Mao, Rong-Rong

    2014-08-01

    Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD. PMID:24746487

  9. Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats.

    PubMed

    Hensleigh, Emily; Pritchard, Laurel M

    2015-12-15

    Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3h per day during the first two weeks of development or 15 min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0mg/kg METH injections every 2h for a total of four injections. Rectal temperatures were taken before the first injection and 1h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage. PMID:25535855

  10. Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone.

    PubMed

    Durrant, Lara M; Khorram, Omid; Buchholz, John N; Pearce, William J

    2014-03-15

    Although the effects of prenatal undernutrition on adult cardiovascular health have been well studied, its effects on the cerebrovascular structure and function remain unknown. We used a pair-fed rat model of 50% caloric restriction from day 11 of gestation to term, with ad libitum feeding after birth. We validated that maternal food restriction (MFR) stress is mediated by glucocorticoids by administering metyrapone, a corticosterone synthesis inhibitor, to MFR mothers at day 11 of gestation. At age 8 mo, offspring from Control, MFR, and MFR + Metyrapone groups were killed, and middle cerebral artery (MCA) segments were studied using vessel-bath myography and confocal microscopy. Colocalization of smooth muscle ?-actin (SM?A) with nonmuscle (NM), SM1 and SM2 myosin heavy-chain (MHC) isoforms was used to assess smooth muscle phenotype. Our results indicate that artery stiffness and wall thickness were increased, pressure-evoked myogenic reactivity was depressed, and myofilament Ca(2+) sensitivity was decreased in offspring of MFR compared with Control rats. MCA from MFR offspring exhibited a significantly greater SM?A/NM colocalization, suggesting that the smooth muscle cells had been altered toward a noncontractile phenotype. MET significantly reversed the effects of MFR on stiffness but not myogenic reactivity, lowered SM?A/NM colocalization, and increased SM?A/SM2 colocalization. Together, our data suggest that MFR alters cerebrovascular contractility via both glucocorticoid-dependent and glucocorticoid-independent mechanisms. PMID:24477541

  11. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    SciTech Connect

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome alterations were associated with glucocorticoid elevation. • Maternal metabonomes were altered at early stage after caffeine exposure. • Maternal glucocorticoid and associated metabolites may be involved in fetal programming.

  12. Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity

    PubMed Central

    Glastras, Sarah J.; Chen, Hui; McGrath, Rachel T.; Zaky, Amgad A.; Gill, Anthony J.; Pollock, Carol A.; Saad, Sonia

    2016-01-01

    Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring. PMID:27004609

  13. Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity.

    PubMed

    Glastras, Sarah J; Chen, Hui; McGrath, Rachel T; Zaky, Amgad A; Gill, Anthony J; Pollock, Carol A; Saad, Sonia

    2016-01-01

    Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring. PMID:27004609

  14. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gmez, F; Segovia, S; Prez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. PMID:26163152

  15. The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

    PubMed

    Kinsley, Craig Howard; Blair, Jamie C; Karp, Natalie E; Hester, Naomi W; McNamara, Ilan M; Orthmeyer, Angela L; McSweeney, Molly C; Bardi, Massimo M; Karelina, Kate; Christon, Lillian M; Sirkin, Maxwell R; Victoria, Lindsay W; Skurka, Danielle J; Fyfe, Christian R; Hudepohl, Margaret B; Felicio, Luciano F; Franssen, R Adam; Meyer, Elizabeth E A; da Silva, Ilton S; Lambert, Kelly G

    2014-09-01

    In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish predation ability--relative to NULLs. Therefore, as with the increasing reports of enhancements to the maternal brain, it is apparent that meaningful behavioral adaptations occur that likewise promote the survival of the mother and her infants at a crucial stage of their lives. PMID:25240277

  16. Effects of Maternal Diet and Exercise during Pregnancy on Glucose Metabolism in Skeletal Muscle and Fat of Weanling Rats

    PubMed Central

    Raipuria, Mukesh; Bahari, Hasnah; Morris, Margaret J.

    2015-01-01

    Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring. PMID:25853572

  17. Effects of maternal diet and exercise during pregnancy on glucose metabolism in skeletal muscle and fat of weanling rats.

    PubMed

    Raipuria, Mukesh; Bahari, Hasnah; Morris, Margaret J

    2015-01-01

    Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1?) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring. PMID:25853572

  18. In utero glucocorticoid exposure reduces fetal skeletal muscle mass in rats independent of effects on maternal nutrition

    PubMed Central

    Gokulakrishnan, Ganga; Estrada, Irma J.; Sosa, Horacio A.

    2012-01-01

    Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n = 7/group) were studied: ad libitum food intake (control, CON); ad libitum food intake with 1 mg dexamethasone/l drinking water from embryonic day (ED)13 to ED21 (DEX); pair-fed (PF) to DEX from ED13 to ED21. On ED22, dams were injected with [3H]phenylalanine for measurements of fetal leg muscle and diaphragm fractional protein synthesis rates (FSR). Fetal muscles were analyzed for protein and RNA contents, [3H]phenylalanine incorporation, and MuRF1 and atrogin-1 (MAFbx) mRNA expression. Fetal liver tyrosine aminotransferase (TAT) expression was quantified to assess fetal exposure to GLCs. DEX treatment reduced maternal food intake by 13% (P < 0.001) and significantly reduced placental mass relative to CON and PF dams. Liver TAT expression was elevated only in DEX fetuses (P < 0.01). DEX muscle protein masses were 56% and 70% than those of CON (P < 0.01) and PF (P < 0.05) fetuses, respectively; PF muscles were 80% of CON (P < 0.01). Muscle FSR decreased by 35% in DEX fetuses (P < 0.001) but were not different between PF and CON. Only atrogin-1 expression was increased in DEX fetus muscles. We conclude that high maternal GLC levels and inadequate maternal food intake impair fetal skeletal muscle growth, most likely through different mechanisms. When combined, the effects of decreased maternal intake and maternal GLC intake on fetal muscle growth are additive. PMID:22422665

  19. In utero glucocorticoid exposure reduces fetal skeletal muscle mass in rats independent of effects on maternal nutrition.

    PubMed

    Gokulakrishnan, Ganga; Estrada, Irma J; Sosa, Horacio A; Fiorotto, Marta L

    2012-05-15

    Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n = 7/group) were studied: ad libitum food intake (control, CON); ad libitum food intake with 1 mg dexamethasone/l drinking water from embryonic day (ED)13 to ED21 (DEX); pair-fed (PF) to DEX from ED13 to ED21. On ED22, dams were injected with [(3)H]phenylalanine for measurements of fetal leg muscle and diaphragm fractional protein synthesis rates (FSR). Fetal muscles were analyzed for protein and RNA contents, [(3)H]phenylalanine incorporation, and MuRF1 and atrogin-1 (MAFbx) mRNA expression. Fetal liver tyrosine aminotransferase (TAT) expression was quantified to assess fetal exposure to GLCs. DEX treatment reduced maternal food intake by 13% (P < 0.001) and significantly reduced placental mass relative to CON and PF dams. Liver TAT expression was elevated only in DEX fetuses (P < 0.01). DEX muscle protein masses were 56% and 70% than those of CON (P < 0.01) and PF (P < 0.05) fetuses, respectively; PF muscles were 80% of CON (P < 0.01). Muscle FSR decreased by 35% in DEX fetuses (P < 0.001) but were not different between PF and CON. Only atrogin-1 expression was increased in DEX fetus muscles. We conclude that high maternal GLC levels and inadequate maternal food intake impair fetal skeletal muscle growth, most likely through different mechanisms. When combined, the effects of decreased maternal intake and maternal GLC intake on fetal muscle growth are additive. PMID:22422665

  20. Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats.

    PubMed

    Bayerl, Doris S; Kaczmarek, Veronika; Jurek, Benjamin; van den Burg, Erwin H; Neumann, Inga D; Gaßner, Barbara M; Klampfl, Stefanie M; Bosch, Oliver J

    2016-03-01

    Recent studies using V1b receptor (V1bR) knockout mice or central pharmacological manipulations in lactating rats highlighted the influence of this receptor for maternal behavior. However, its role in specific brain sites known to be important for maternal behavior has not been investigated to date. In the present study, we reveal that V1bR mRNA (qPCR) and protein levels (Western blot) within either the medial preoptic area (MPOA) or the medial-posterior part of the bed nucleus of the stria terminalis (mpBNST) did not differ between virgin and lactating rats. Furthermore, we characterized the effects of V1bR blockade via bilateral injections of the receptor subtype-specific antagonist SSR149415 within the MPOA or the mpBNST on maternal behavior (maternal care under non-stress and stress conditions, maternal motivation to retrieve pups in a novel environment, maternal aggression) and anxiety-related behavior in lactating rats. Blocking V1bR within the MPOA increased pup retrieval, whereas within the mpBNST it decreased pup-directed behavior, specifically licking/grooming the pups, during the maternal defense test. In addition, immediately after termination of the maternal defense test, V1bR antagonism in both brain regions reduced nursing, particularly arched back nursing. Anxiety-related behavior was not affected by V1bR antagonism in either brain region. In conclusion our data indicate that V1bR antagonism significantly modulates different aspects of maternal behavior in a brain region-dependent manner. PMID:26747375

  1. Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model.

    PubMed

    Dvorak, Bohuslav; Halpern, Melissa D; Holubec, Hana; Dvorakova, Katerina; Dominguez, Jessica A; Williams, Catherine S; Meza, Yolanda G; Kozakova, Hana; McCuskey, Robert S

    2003-03-01

    Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of rat milk (RM)-versus cow milk-based rat milk substitute (RMS) on the development of NEC in a neonatal rat model and elucidate the role of inflammatory cytokines in NEC pathogenesis. Newborn rats were artificially fed with either collected RM or RMS. Experimental NEC was induced by exposure to asphyxia and cold stress and evaluated by histologic scoring of damage in ileum. Intestinal cytokine mRNA expression was determined by real-time PCR. Cytokine histologic localization was performed by confocal microscopy. Similar to human NEC, artificial feeding of RM reduces the incidence and severity of NEC injury in neonatal rats. Freezing and thawing of collected RM did not eliminate the protective effect of maternal milk. Ileal IL-10 expression was significantly increased in the RM group compared with RMS. Increased IL-10 peptide production was detected in the RM group with signal localized predominantly in the cytoplasm of villus epithelial cells. These results suggest that the protective effect of maternal milk is associated with increased production of anti-inflammatory IL-10 in the site of injury. Better understanding of the mechanisms underlying these protective effects could be beneficial either in the prevention of NEC or in the development of future therapeutic strategies to cure NEC. PMID:12595590

  2. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele

    PubMed Central

    Ye, Xiaojing; Kohtz, Amy; Pollonini, Gabriella; Riccio, Andrea; Alberini, Cristina M.

    2015-01-01

    Insulin like growth factor 2 (Igf2) is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain. PMID:26495851

  3. Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

    PubMed

    Figueiredo, Mariana Sarto; da Conceição, Ellen Paula Santos; de Oliveira, Elaine; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar

    2015-10-14

    Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and adrenaline β2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11β-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11β-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during lactation. PMID:26337632

  4. The effect of protein restriction on the progression of renal insufficiency

    SciTech Connect

    Ihle, B.U.; Becker, G.J.; Whitworth, J.A.; Charlwood, R.A.; Kincaid-Smith, P.S. )

    1989-12-28

    Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure.

  5. Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt-Sensitive Rat.

    PubMed

    Gillis, Ellen E; Mooney, Jennifer N; Garrett, Michael R; Granger, Joey P; Sasser, Jennifer M

    2016-03-01

    Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. There is currently no effective treatment, but sildenafil, a phosphodiesterase-5 inhibitor, has been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. We hypothesized that sildenafil would improve the maternal syndrome and fetal outcomes in the Dahl S rat model of superimposed preeclampsia. Dahl S rats were mated, and half received sildenafil (50 mg/kg per day, via food) from day 10 through day 20 of pregnancy. The untreated Dahl S rats had a significant rise in blood pressure and a 2-fold increase in urinary protein excretion from baseline to late pregnancy; however, sildenafil-treated Dahl S rats exhibited ≈40 mm Hg drops in blood pressure with no rise in protein excretion. Sildenafil also increased creatinine clearance and reduced nephrinuria and glomerulomegaly. Sildenafil treatment reduced the uterine artery resistance index during late pregnancy in the Dahl S rat and improved fetal outcomes (survival, weight, and litter size). In addition, 19% of all pups were resorbed in untreated rats, with no incidence of resorptions observed in the treated group. Furthermore, tumor necrosis factor-α, endothelin-1, and oxidative stress, which are characteristically increased in women with preeclampsia and in experimental models of the disease, were reduced in treated rats. These data suggest that sildenafil improves the maternal syndrome of preeclampsia and blood flow to the fetoplacental unit, providing preclinical evidence to support the hypothesis that phosphodiesterase type 5 inhibition may be an important therapeutic target for the treatment of preeclampsia. PMID:26729752

  6. Influence of the destabilisation of the maternal digestive microflora on that of the newborn rat.

    PubMed

    Brunel, A; Gouet, P

    1993-01-01

    By destabilising the digestive flora of pregnant rats by antibiotic treatment, it was shown that part of the digestive microflora of the neonate originated from the maternal faeces. A mixture of ampicillin, bacitracin neomycin and streptomycin associated with nystatin were administered ad libitum at three different times, 1-3, 3-5, and more than 5 days before the estimated date of littering. For each treatment, samples were taken from the faeces, teats, and vagina of dams and from the digestive tracts of neonates aged between 6 and 120 h, and analysed for the presence of staphylococci, enterococci, lactobacilli and coliform bacteria. Antibiotic treatment reduced digestive flora populations to levels lower than 10(2) g-1 but had less effect on the vaginal and cutaneous mammary flora. In the digestive microflora of the neonate, the enterococci were unevenly affected, whereas the staphylococci were considerably decreased and the lactobacilli almost completely eliminated; coliform bacteria were found sporadically and in small numbers. The traces of antibiotics found in milk are not sufficient to explain these modifications. Counts made in control animals on media fed the same antibiotic concentrations were not modified. This work underlined the awful consequences for the newborn of a serious perturbation of the mother flora and the necessity of its presence for a normal installation of the digestive microflora of the newborn. PMID:8513029

  7. A methyl-seq analyses of rat offspring liver reveals maternal obesity-induced alterations in dna methylation status at weaning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to maternal obesity (MO) increases the risk of obesity in adult-life. MO was induced in rats by overfeeding via total enteral nutrition. Male offspring from obese rats gain greater body weight, fat mass and develop insulin resistance when fed high fat diets. However the mechanisms underlyin...

  8. EFFECTS ON THE FETAL RAT INTESTINE OF MATERNAL MALNUTRITION AND EXPOSURE TO NITROFEN (2,4-DICHLOROPHENYL-P-NITROPHENYL ETHER)

    EPA Science Inventory

    The effects of maternal protein-energy malnutrition and exposure to nitrofen on selected aspects of intestinal morphology and function were studied in the fetal rat. Pregnant rats were fed, throughout gestation, diets containing 24% or 6% casein as the sole source of protein. Red...

  9. Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine.

    PubMed

    Benetti, Fernando; Mello, Pmela Billig; Bonini, Juliana Sartori; Monteiro, Siomara; Cammarota, Martn; Izquierdo, Ivn

    2009-02-01

    Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lvy et al. (2003) [Lvy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems. PMID:18948184

  10. Maternal Nicotine Exposure Leads to Impaired Disulfide Bond Formation and Augmented Endoplasmic Reticulum Stress in the Rat Placenta

    PubMed Central

    Wong, Michael K.; Nicholson, Catherine J.; Holloway, Alison C.; Hardy, Daniel B.

    2015-01-01

    Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation—a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar rats received daily subcutaneous injections of either saline (vehicle) or nicotine bitartrate (1 mg/kg) for 14 days prior to mating and during pregnancy. Placentas were harvested on embryonic day 15 for analysis. Protein and mRNA expression of markers involved in ER stress (e.g., phosphorylated eIF2α, Grp78, Atf4, and CHOP), disulfide bond formation (e.g., PDI, QSOX1, VKORC1), hypoxia (Hif1α), and amino acid deprivation (GCN2) were quantified via Western blot and/or Real-time PCR. Maternal nicotine exposure led to increased expression of Grp78, phosphorylated eIF2α, Atf4, and CHOP (p<0.05) in the rat placenta, demonstrating the presence of augmented ER stress. Decreased expression of PDI and QSOX1 (p<0.05) reveal an impaired disulfide bond formation pathway, which may underlie nicotine-induced ER stress. Finally, elevated expression of Hif1α and GCN2 (p<0.05) indicate hypoxia and amino acid deprivation in nicotine-exposed placentas, respectively, which may also cause impaired disulfide bond formation and augmented ER stress. This study is the first to link maternal nicotine exposure with both placental ER stress and disulfide bond impairment in vivo, providing novel insight into the mechanisms underlying nicotine exposure during pregnancy on placental health. PMID:25811377

  11. Maternal Deprivation Enhances Behavioral Vulnerability to Stress Associated with miR-504 Expression in Nucleus Accumbens of Rats

    PubMed Central

    Zhang, Yi; Zhu, Xiongzhao; Bai, Mei; Zhang, Li; Xue, Liang; Yi, Jinyao

    2013-01-01

    Objective In this study, the effect of maternal deprivation (MD) and chronic unpredictable stress (CUS) in inducing depressive behaviors and associated molecular mechanism were investigated in rats. Methods Maternal deprivation was established by separating pups from their mothers for 6 hours daily from postnatal day 1 to day 14. Chronic unpredictable stress was established by water deprivation, elevated open platform, food deprivation, restraint stress and electric foot shock. The depressive behaviors were determined by use of sucrose preference test and forced swim test. Results Rats in MD/CUS group exhibited lower sucrose preference rate, longer immobility time, and lighter body weights than rats in other groups (MD/control, non-MD/CUS and non-MD/control group). Meanwhile, higher miR-504 expression and lower dopamine receptor D1 (DRD1) and D2 (DRD2) expression were observed in the nucleus accumbens of rats in the MD/CUS group than in the other three groups. MiR-504 expression correlated negatively with DRD1 gene expression and sucrose preference rate in the sucrose preference test, but correlated positively with immobility time in forced swim test. Both DRD2 mRNA and protein expression correlated negatively with immobility time in forced swim test. Conclusion These results suggest that MD enhances behavioral vulnerability to stress during adulthood, which is associated with the upregulation of miR-504 and downregulation of DRD2 expression in the nucleus accumbens. PMID:23922862

  12. Diabetes in Old Male Offspring of Rat Dams Fed a Reduced Protein Diet

    PubMed Central

    Dorling, Matthew W.; Pawlak, Dorota B.; Ozanne, Susan E.; Hales, C. Nicholas

    2001-01-01

    Restricted fetal growth is associated with increased risk for the future development of Type 2 diabetes in humans. The study aim was to assess the glucose tolerance of old (seventeen months) male rats, which were growth restricted in early life due to maternal protein restriction during gestation and lactation. Rat mothers were fed diets containing either 20% or 8% protein and all offspring weaned onto a standard rat diet. In old-age fasting plasma glucose concentrations were significantly higher in the low protein offspring: 8.4 (1.3)mmol/l v. 5.3 (1.3)mmol/l (p = 0.005), Areas under the curves were increased by 67% for glucose (p = 0.01) and 81% for insulin (p = 0.01) in these rats in intravenous glucose tolerance tests, suggesting (a degree of) insulin resistance. These results show that early growth retardation due to maternal protein restriction leads to the development of diabetes in old male rat offspring. The diabetes is predominantly associated with insulin resistance. PMID:12369717

  13. Effect of melatonin and stobadine on maternal and embryofoetal toxicity in rats due to intrauterine hypoxia induced by phenytoin administration.

    PubMed

    Ujhzy, E; Mach, M; Dubovick, M; Navarov, J; Solts, L; Jurnek, I; Brucknerov, I; Zeman, M

    2004-03-01

    The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (MEL) and the synthetic antioxidant stobadine (STO) could reduce the incidence of maternal and embryofoetal toxicity in rats due to intrauterine hypoxia. Chronic hypoxia was induced pharmacologically by the administration of the anticonvulsant phenytoin (PHT) during the entire period of pregnancy. PHT disturbed the normal course of pregnancy, affected reproductive parameters and increased the incidence of skeletal anomalies. MEL did not protect the PHT-induced development toxicity in rat. On the other hand, STO partially prevented PHT-induced reduction of foetal and placental weights. Administration of STO also decreased the frequency of pre- and post-implantation loss and resorptions in the PHT group. We concluded that pretreatment of pregnant rats with STO prevented to a certain extent reproductive and foetal development alterations caused by chronic intrauterine hypoxia. PMID:15141990

  14. Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1-mediated thermogenesis.

    PubMed

    Claycombe, Kate J; Vomhof-DeKrey, Emilie E; Roemmich, James N; Rhen, Turk; Ghribi, Othman

    2015-07-01

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT thermogenesis and BW of offspring in utero is not yet known. We fed obese-prone Sprague-Dawley dams 8% LP or 20% normal protein (NP) diets for 3 weeks prior to breeding and through pregnancy. BW and gene expression of interscapular BAT (iBAT) thermogenic markers were measured in male fetal (gestation day 18) and neonatal (day 0 or 1) offspring. BW of neonatal LP males was lower than NP males but no difference was observed in females. Gene and protein expression of UCP-1 and transcription factors PRDM16 and PPARα in iBAT were 2- to 6-fold greater in LP than in NP male neonatal offspring. FNDC5, a precursor of irisin and activator of thermogenesis, was expressed 2-fold greater in neonatal LP iBAT than NP males. However, fetal iBAT UCP-1, PRDM16, PPARα and irisin mRNA did not differ between LP and NP groups. Maternal LP diet had no effects on placental irisin and UCP-2 expression. These results suggest that prenatal protein restriction increases the risk for low BW through mechanisms affecting full-term offspring iBAT thermogenesis but not greatly altering fetal iBAT or placental thermogenesis. PMID:25858881

  15. Histamine acting on the basolateral amygdala reverts the impairment of aversive memory of rats submitted to neonatal maternal deprivation.

    PubMed

    Benetti, Fernando; da Silveira, Clarice Kras Borges; Rosa, Jessica; Izquierdo, Ivan

    2015-02-01

    Recent findings suggest a role of brain histamine in the regulation of memory consolidation, particularly in one-trial inhibitory avoidance (IA) learning and that disruption in the mother infant relationship i.e. maternal deprivation induces cognitive deficits. We investigate whether histamine itself, and histaminergic compounds given into the basolateral amygdala (BLA) immediately post-training can affect retention (24 h after training) of one-trial (IA) in rats submitted to early postnatal maternal deprivation. In all cases, deprived (Dep) animals had lower retention scores than non-deprived controls (N-dep). Histamine induced memory enhancement on its own in N-dep animals and was able to overcome the deleterious effect of Dep. The effects by SKF-91488 is similar to histamine. The H3 agonist, imetit mimetized the enhancing effects of histamine; neither agonist H1 pyridylethylamine nor the H2 dimaprit had any effect. Ranitidine and thioperamide (50 nmol) co-infused with histamine (10 nmol) fully blocked the restorative effect of histamine on retention in Dep animals. Thioperamide, in addition, blocked the enhancing effect of histamine on memory of the N-dep animals as well. None of the drugs used given into BLA had any effect on open-field or elevated plus-maze behavior in N-dep or Dep rats. Our results are limited to experimental design in rats. Extrapolation i.e. in humans requires further experimentations. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may at least in part be due to an impairment of histamine H3 receptor-mediated mediated mechanisms in the BLA. PMID:25257105

  16. Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis.

    PubMed

    Khan, Galam; Penttinen, Pauliina; Cabanes, Anna; Foxworth, Aaron; Chezek, Antonia; Mastropole, Kristen; Yu, Bin; Smeds, Annika; Halttunen, Teemu; Good, Carolyn; Mkel, Sari; Hilakivi-Clarke, Leena

    2007-01-01

    Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 25) might affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-alpha protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-beta protein levels in the terminal end buds (TEBs) lobules and ducts. Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the epithelial structures. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was six-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-beta content was causally linked to increased mammary cancer risk among the offspring. PMID:17398067

  17. Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model.

    PubMed

    Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S

    2015-12-01

    Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. PMID:26631470

  18. Evaluation of rat in vivo fetal-to-maternal transfer clearances of various xenobiotics by umbilical perfusion.

    PubMed

    Nishimura, Tomohiro; Takanohashi, Tatsuya; Tomi, Masatoshi; Horikoshi, Miho; Higuchi, Kei; Sai, Yoshimichi; Nakashima, Emi

    2013-09-01

    It is important to address the tissue permeability of drugs, particularly in tissues that have a blood-tissue barrier, in terms of both lipophilicity and the contribution of transporters. Here, we employed umbilical perfusion in rats to evaluate in vivo fetal-to-maternal transfer clearances of various xenobiotics. We measured fetal-to-maternal clearance (CLfm ) of 23 compounds, which have a broad range of lipophilicity. Drugs for which CLfm was more than 300 µL/(mL min) belonged exclusively to Biopharmaceutical Drug Disposition Classification System (BDDCS) class 1 (highly permeable) and those for which CLfm was less than 50 µL/(mL min) belonged exclusively to BDDCS class 3 (poorly permeable). For most drugs, CLfm values were broadly consistent with lipophilicity. However, CLfm of digoxin was saturable and was inhibited by verapamil, suggesting that P-glycoprotein (P-gp)-mediated efflux has a substantially effect on measured clearance. CLfm of mitoxantrone continued to increase slightly at high concentrations of mitoxantrone, but placental-to-maternal clearance of mitoxantrone was saturable, implying that Bcrp1 contributes to mitoxantrone efflux across the placenta. Thus, we measured CLfm by umbilical perfusion and examined the relationship between CLfm and lipophilicity of xenobiotics. Fetal-to-maternal transport clearances measured in this study will be helpful to understand the characteristics of the blood-placental barrier. PMID:23620249

  19. Postnatal undernutrition in rats: attempts to develop alternative methods to food deprive pups without maternal behavioral alteration.

    PubMed

    Codo, W; Carlini, E A

    1979-09-01

    Two methods were investigated as attempts to undernourish rat pups without the disturbances in maternal behavior that accompany the procedures used to date for this purpose. In the 1st method, a litter of 12 pups was raised by both a lactating mother and a "sensitized" female. The sensitized female was provided under the assumption that she could correct for the deficit in maternal care when 1 mother raises a large litter. The results showed that the pups raised by the 2 females were constantly removed by the females from each other's nests; the females engaged in constant fighting and showed altered maternal behavior. As a consequence the pups lost more weight than control underfed young. The 2nd method consisted of removing 6-8 nipples from virgin females which were mated 10 days later. After delivery these females raised litters of 6 pups. Their maternal behavior was equal to that of unoperated controls, and at weaning the pups had 20-50% less body weight. This method could be useful to study undernutrition effects on behavior, without confounding experimental variables. PMID:488531

  20. Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour.

    PubMed

    Paternain, Laura; Martisova, Eva; Campión, Javier; Martínez, J Alfredo; Ramírez, Maria J; Milagro, Fermin I

    2016-02-15

    Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDL-cholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain. PMID:26628207

  1. Maternal Contact Differentially Modulates Central and Peripheral Oxytocin in Rat Pups During a Brief Regime of Mother–Pup Interaction that Induces a Filial Huddling Preference

    PubMed Central

    Kojima, S.; Stewart, R. A.; Demas, G. E.; Alberts, J. R.

    2014-01-01

    Central oxytocin mediates the acquisition of a filial preference for maternal odour in rat pups, manifested by their huddling preferences. The present study was designed to examine whether maternal care modulates oxytocin concentrations in rat pups and, if so, how different types of maternal contact are associated with the pups’ oxytocin concentrations. Pairs of 14-day-old littermates were removed from their home cage for 1 h and then placed with a lactating foster mother for 2 h, or they remained isolated at room temperature. Enzyme immunoassays revealed that maternal care and maternal separation can differentially modulate pups’ oxytocin concentrations. Both hypothalamic and serum oxytocin increased during the 1-h separation. Pups placed with a foster mother after the separation maintained the same concentrations in the hypothalamus and serum through the fostering period. By contrast, pups placed with no mother showed a further increase in hypothalamic oxytocin but serum oxytocin decreased. Behavioural analyses revealed that skin-to-skin contact with the mother, but not simple physical contact or maternal licking / grooming, was positively correlated with the pups’ hypothalamic oxytocin concentrations. These neuroendocrine data match previous findings showing that skin-to-skin contact with mother facilitates the acquisition of the pups’ huddling preference for a maternally-associated odour. Taken together, the present study suggests that maternal skin-to-skin contact stimulates pups’ central oxytocin, at the same time as creating the conditions for inducing a preference for maternal odour and establishing a social affiliation in rat pups; the natural schedule of maternal separation and reunion may modulate pups’ oxytocin concentrations, providing scaffolding for the acquisition of their filial huddling preference. PMID:22260655

  2. Maternal separation interferes with developmental changes in brain vasopressin and oxytocin receptor binding in male rats.

    PubMed

    Lukas, M; Bredewold, R; Neumann, I D; Veenema, A H

    2010-01-01

    Brain vasopressin V(1A) receptors (V(1A)-R) and oxytocin receptors (OT-R) are important modulators of social behaviors. We recently showed that exposure to maternal separation (MS; 3 h daily, postnatal days 1-14) induces changes in social behaviors in juvenile and adult male rats. Here, we hypothesize that MS induces brain region-specific changes in V(1A)-R and OT-R across development, which in turn, may underlie MS-induced changes in social behaviors. We examined the effects of MS on V(1A)-R and OT-R binding in forebrain regions of juvenile (5 weeks), adolescent (8 weeks), and adult (16 weeks) male rats. Robust age-related changes were found for V(1A)-R and OT-R binding in several brain regions. For example, in the lateral septum V(1A)-R binding increased while OT-R binding decreased with age. Most notably, OT-R binding in the caudate putamen showed a 2-fold decrease while OT-R binding in the ventromedial hypothalamus showed a 4-fold increase with age. Importantly, exposure to MS interfered with these developmental changes in several brain regions. Specifically, MS significantly increased V(1A)-R binding in the piriform cortex (at adolescent and adult ages), the lateral septum (at juvenile age), the hypothalamic attack area (at adolescent age), and the dentate gyrus of the hippocampus (at adolescent age), and decreased V(1A)-R binding in the arcuate nucleus (at juvenile age). Moreover, OT-R binding was significantly lower in the agranular cortex (at juvenile and adolescent age), the lateral septum (at adult age) and the caudate putamen (at adult age), but higher in the medial preoptic area (at adolescent age) and ventromedial hypothalamus (at adult age) after exposure to MS. In conclusion, age-dependent changes in V(1A)-R and OT-R binding are likely associated with the maturation of behaviors, such as sexual and aggressive behaviors, while disruption of these changes by MS might contribute to previously observed changes in social behaviors after MS. PMID:19560475

  3. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  4. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. PMID:26385575

  5. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation

    PubMed Central

    Gareau, Mélanie G; Jury, Jennifer; MacQueen, Glenda; Sherman, Philip M; Perdue, Mary H

    2007-01-01

    Background We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long‐term changes in intestinal physiology. Aim To examine if administration of probiotics affects MS‐induced gut dysfunction. Methods MS pups were separated from the dam for 3 h/day from days 4 to 19; non‐separated (NS) pups served as controls. Twice per day during the separation period, 108 probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle‐treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus–pituitary–adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short‐circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60. Results Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS‐induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20. Conclusions The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity. PMID:17339238

  6. Maternal high-fat diet increases independent feeding in pre-weanling rat pups.

    PubMed

    Kojima, Sayuri; Catavero, Christina; Rinaman, Linda

    2016-04-01

    In laboratory settings, the adult offspring of rodent dams that are maintained on high-fat diet (HFD) before conception and/or during pregnancy/lactation display an increased incidence of obese phenotypic markers, including increased body weight and adiposity, reduced leptin sensitivity, and impaired glucose tolerance. In rat pups raised by dams consuming HFD, these obese markers emerge during the first postnatal week. Since the week-old offspring of HFD dams consume excess amounts of milk during experimental tests of independent feeding (i.e., intake away from the dam), we hypothesized that maternal diet affects suckling and/or independent ingestion by pups in the home-cage environment. In the present study, this hypothesis was tested by conducting detailed analyses of ingestive behaviors expressed by pups in the home cage. Pups raised by dams consuming HFD displayed an earlier onset of independent feeding and more amounts of calorie intake from solid food during the third postnatal week compared to pups raised by dams consuming regular chow, with no diet-related differences in suckling behavior. Independent ingestion by pups in both diet groups was most frequently observed after nursing, with offspring of HFD dams engaged more frequently in post-nursing independent feeding episodes compared to offspring of chow-fed dams, particularly when the prior nursing episode was nutritive (i.e., including milk receipt by pups). We conclude that early-life exposure to HFD enhances the facilitative effect of nutritive suckling on independent feeding in pups, promoting increased caloric intake from solid food in the home-cage environment. PMID:26873412

  7. Importance of maternal diabetes on the chronological deregulation of the intrauterine development: an experimental study in rat.

    PubMed

    Salazar Garca, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, Mara Cristina; Villavicencio Guzmn, Laura; Reyes Lpez, Alfonso; Snchez-Gmez, Concepcin

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ?1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

  8. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    PubMed Central

    Salazar Garca, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, Mara Cristina; Villavicencio Guzmn, Laura; Reyes Lpez, Alfonso; Snchez-Gmez, Concepcin

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ?1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

  9. Maternal behavior induced in male rats by bilateral lesions of the bed nucleus of the accessory olfactory tract.

    PubMed

    Izquierdo, M A; Collado, P; Segovia, S; Guillamón, A; del Cerro, M C

    1992-10-01

    In the present study, we investigate the effect of bilateral electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) in male Wistar rats that did not have care-pups experience, using a test of induced maternal behavior. Consistent with our previous findings in virgin female rats (10), there was a significantly shorter sensitization (3 days) and retrieval (2 days) latencies in the BAOT-lesioned group than in the sham-lesioned and intact-control male groups (12 days for both). Based on these findings, we propose that BAOT, a sexually dimorphic nucleus of the vomeronasal system, exerts an inhibitory modulation in the expression of parental behavior in male and female virgin rats. It may do so by maintaining an olfactory-based tonic inhibition of maternal behavior, thereby resulting in the adults' tonic avoidance of the pups until this inhibition is abolished by lesion, or reduced or overridden by appropriate hormonal and/or sensory influences. PMID:1409941

  10. Early maternal deprivation alters hippocampal levels of neuropeptide Y and calcitonin-gene related peptide in adult rats.

    PubMed

    Husum, H; Termeer, E; Math, A A; Bolwig, T G; Ellenbroek, B A

    2002-05-01

    Stressful events early in life are reported to be more prevalent among patients with an adult life psychiatric disorder. Early maternal deprivation is considered an animal model of early life stress. Maternally deprived adult rats display long-term alterations in the neuroendocrine system, brain and behavior that are in many ways analogous to depressive and schizophrenic symptomatology. Neuropeptide Y (NPY) and calcitonin-gene related peptide (CGRP) have been implicated in both disorders and also been suggested to play a role in the neuroadaptational response to stress. Consequently, male Wistar rat-pups were subjected to early maternal deprivation or control handling, on postnatal day (pnd) 9. On pnd 21, pups were weaned and split into two groups that were reared either on a saw-dust floor or on a grid-floor, considered to be a mild stressor. On pnd 67, all animals were subjected to the prepulse inhibition test. One week later, the animals were sacrificed, the brains removed and dissected on ice. Levels of NPY-like immunoreactivity (LI) and CGRP-LI were quantified by radioimmunoassay in brain regional extracts. Maternal deprivation led to a significant reduction in basal startle amplitude and disruption of prepulse inhibition. These findings were paralleled by significantly reduced levels of NPY and CGRP in the hippocampus and occipital cortex. It is hypothesised that these changes may be of relevance to aspects of schizophrenic and affective symptomatology. The present study further shows that brain NPY and, in particular, CGRP are sensitive to long-term mild stress and further implicate the involvement of these peptides in the neuroendocrine stress response. PMID:12015206

  11. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    PubMed Central

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification. PMID:26696906

  12. Toxic Effects of Maternal Zearalenone Exposure on Intestinal Oxidative Stress, Barrier Function, Immunological and Morphological Changes in Rats

    PubMed Central

    Liu, Min; Gao, Rui; Meng, Qingwei; Zhang, Yuanyuan; Bi, Chongpeng; Shan, Anshan

    2014-01-01

    The present study was conducted to investigate the effects of maternal zearalenone (ZEN) exposure on the intestine of pregnant Sprague-Dawley (SD) rats and its offspring. Ninety-six pregnant SD rats were randomly divided into four groups and were fed with diets containing ZEN at concentrations of 0.3 mg/kg, 48.5 mg/kg, 97.6 mg/kg or 146.0 mg/kg from gestation days (GD) 1 to 7. All rats were fed with mycotoxin-free diet until their offspring were weaned at three weeks of age. The small intestinal fragments from pregnant rats at GD8, weaned dams and pups were collected and studied for toxic effects of ZEN on antioxidant status, immune response, expression of junction proteins, and morphology. The results showed that ZEN induced oxidative stress, affected the villous structure and reduced the expression of junction proteins claudin-4, occludin and connexin43 (Cx43) in a dose-dependent manner in pregnant rats. Different effects on the expression of cytokines were also observed both in mRNA and protein levels in these pregnant groups. Ingestion of high levels of ZEN caused irreversible damage in weaned dams, such as oxidative stress, decreased villi hight and low expression of junction proteins and cytokines. Decreased expression of jejunal interleukin-8 (IL-8) and increased expression of gastrointestinal glutathione peroxidase (GPx2) mRNA were detected in weaned offspring, indicating long-term damage caused by maternal ZEN. We also found that the Nrf2 expression both in mRNA and protein levels were up-regulated in the ZEN-treated groups of pregnant dams and the high-dose of ZEN group of weaned dams. The data indicate that modulation of Nrf2-mediated pathway is one of mechanism via which ZEN affects gut wall antioxidant and inflammatory responses. PMID:25180673

  13. Fructose intake during pregnancy up-regulates the expression of maternal and fetal hepatic sterol regulatory element-binding protein-1c in rats.

    PubMed

    Mukai, Yuuka; Kumazawa, Maya; Sato, Shin

    2013-08-01

    Excess fructose consumption is associated with the development of type 2 diabetes and obesity. However, the impact of fructose intake on maternal and fetal lipid metabolism during pregnancy is not known. The aim of this study was to examine whether maternal fructose intake during pregnancy would affect fetal and maternal hepatic lipid metabolism. Pregnant Wistar rats were randomly divided into untreated control and fructose-treated groups; the fructose-treated group received fructose via drinking water throughout pregnancy. On gestational day 20, glucose and insulin concentration in the maternal plasma were measured. The mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and its target genes in the liver of dams and fetuses were analyzed by real-time PCR. Significantly higher maternal plasma glucose levels, indicating hyperglycemia, was observed in the fructose-treated group than in the control group. Furthermore, the fructose-treated group showed significantly higher expression levels of both maternal and fetal SREBP-1c mRNA and protein and significantly elevated expression of fatty acid synthase; the group also showed reduced acyl-CoA oxidase levels in the maternal liver. Thus, our results suggest that maternal fructose intake during pregnancy causes maternal hyperglycemia and up-regulates hepatic SREBP-1c expression in both fetuses and dams. This may lead to defects in carbohydrate and lipid metabolism in the adult offspring. PMID:23065593

  14. Maternal high fat and/or salt consumption induces sex-specific inflammatory and nutrient transport in the rat placenta

    PubMed Central

    Reynolds, Clare M; Vickers, Mark H; Harrison, Claudia J; Segovia, Stephanie A; Gray, Clint

    2015-01-01

    Maternal high fat and salt consumption are associated with developmental programming of disease in adult offspring. Inadequacies in placental nutrient transport may explain these programmed effects. Diet-induced inflammation may have detrimental effects on placental function leading to alteration of key nutrient transporters. We examined the effects of maternal high fat and/or salt diets on markers of placental nutrient transport and inflammation. SpragueDawley rats were assigned to (1) control (CD; 1% Salt 10% kcal from fat); (2) high salt (SD; 4% salt, 10% kcal from fat); (3) high fat (HF; 1% Salt 45% kcal from fat) or (4) high fat high salt (HFSD; 4% salt, 45% kcal from fat) 21days prior to and throughout gestation. At embryonic day 18, dams were killed by isoflurane anesthesia followed by decapitation; placenta/fetuses were weighed, sexed, and collected for molecular analysis. Maternal SD, HF, and HFSD consumption decreased weight of placenta derived from male offspring; however, weight of placenta derived from female offspring was only reduced with maternal HF diet. This was associated with increased expression of LPL, SNAT2, GLUT1, and GLUT4 in placenta derived from male offspring suggesting increased fetal exposure to free fatty acids and glucose. Maternal SD, HF, and HFSD diet consumption increased expression of proinflammatory mediators IL-1?, TNF?, and CD68 in male placenta. Our results suggest that a proinflammatory placental profile results in detrimental alterations in nutrient transport which may contribute to the developmental origins of cardio-metabolic disturbances in offspring throughout life. PMID:25991721

  15. Maternal prenatal undernutrition programs adipose tissue gene expression in adult male rat offspring under high-fat diet.

    PubMed

    Lukaszewski, Marie-Amlie; Mayeur, Sylvain; Fajardy, Isabelle; Delahaye, Fabien; Dutriez-Casteloot, Isabelle; Montel, Valrie; Dickes-Coopman, Anne; Laborie, Christine; Lesage, Jean; Vieau, Didier; Breton, Christophe

    2011-09-01

    Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard diet. We investigated biological parameters as well as gene expression profile focusing on white adipose tissues (WAT) of adult offspring. FR30 procedure does not worsen the metabolic syndrome features induced by HF diet. However, FR30HF rats displayed catch-up growth to match the body weight of adult control HF animals, suggesting an increase of adiposity while showing hyperleptinemia and a blunted increase of corticosterone. Using quantitative RT-PCR array, we demonstrated that FR30HF rats exhibited leptin and Ob-Rb as well as many peptide precursor and receptor gene expression variations in WAT. We also showed that the expression of genes involved in adipogenesis was modified in FR30HF animals in a depot-specific manner. We observed an opposite variation of STAT3 phosphorylation levels, suggesting that leptin sensitivity is modified in WAT adult FR30 offspring. We demonstrated that 11?-HSD1, 11?-HSD2, GR, and MR genes are coexpressed in WAT and that FR30 procedure modifies gene expression levels, especially under HF diet. In particular, level variation of 11?-HSD2, whose protein expression was detected by Western blotting, may represent a novel mechanism that may affect WAT glucocorticoid sensitivity. Data suggest that maternal undernutrition differently programs the adult offspring WAT gene expression profile that may predispose for altered fat deposition. PMID:21712534

  16. Maternal perinatal undernutrition programs a "brown-like" phenotype of gonadal white fat in male rat at weaning.

    PubMed

    Delahaye, Fabien; Lukaszewski, Marie-Amlie; Wattez, Jean-Sbastien; Cisse, Ouma; Dutriez-Casteloot, Isabelle; Fajardy, Isabelle; Montel, Valrie; Dickes-Coopman, Anne; Laborie, Christine; Lesage, Jean; Breton, Christophe; Vieau, Didier

    2010-07-01

    Several studies indicate that maternal undernutrition sensitizes the offspring to the development of metabolic disorders, such as obesity. Using a model of perinatal maternal 50% food-restricted diet (FR50), we recently reported that rat neonates from undernourished mothers exhibit decreased leptin plasma levels associated with alterations of hypothalamic proopiomelanocortin system. The present study aimed at examining the consequences of FR50 on the brain-adipose axis in male rat neonates. Using quantitative RT-PCR array containing 84 obesity-related genes, we demonstrated that most of the genes involved in energy metabolism regulation are expressed in rat gonadal white adipose tissue (WAT) and are sensitive to maternal perinatal undernutrition (MPU). In contrast, hypothalamic gene expression was not substantially affected by MPU. Gene expression of uncoupling protein 1 (UCP1), a marker of brown adipocytes, showed an almost 400-fold stimulation in postnatal day 21 (PND21) FR50 animals, suggesting that their gonadal WAT possesses a brown-like phenotype. This was confirmed by histological and immunoshistochemical procedures, which demonstrated that PND21 FR50 gonadal adipocytes are multilocular, resembling those present in interscapular brown adipose tissue, and exhibit an overexpression of UCP1 and neuropeptide Y (NPY) at the protein level. Control animals contained almost exclusively "classical" unilocular white adipocytes that did not show high UCP1 and NPY labeling. After weaning, FR50 animals exhibited a transient hyperphagia that was associated with the disappearance of brown-like fat pads in PND30 WAT. Our results demonstrate that MPU delays the maturation of gonadal WAT during critical developmental time windows, suggesting that it could have long-term consequences on body weight regulation in the offspring. PMID:20463183

  17. Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats.

    PubMed

    Beery, Annaliese K; McEwen, Lisa M; MacIsaac, Julia L; Francis, Darlene D; Kobor, Michael S

    2016-01-01

    This article is part of a Special Issue "Parental Care". Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr DNA methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by "high" licking-grooming (HL) and "low" licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr DNA methylation was significantly lower at multiple CpGs in the blood of LL versus HL males, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in DNA methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr DNA methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation. PMID:26122287

  18. Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

    PubMed

    Cervantes-Rodrguez, M; Martnez-Gmez, M; Cuevas, E; Nicols, L; Casteln, F; Nathanielsz, P W; Zambrano, E; Rodrguez-Antoln, J

    2014-02-01

    Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion. PMID:24124655

  19. Effect of maternal obstructive cholestasis during pregnancy on the biliary transport of horseradish peroxidase in the rat offspring.

    PubMed

    Monte, Maria J; Villanueva, Gloria R; Macias, Rocio I R; Vazquez, David J; Toledo, Marta; Dominguez, Mercedes; Marin, Jose J G

    2003-09-01

    MOCP (maternal obstructive cholestasis during pregnancy) induces a reversible impairment in bile formation in young rats born to these mothers. The aim of the present study was to gain information on the effects of MOCP on the maturation of pathways involved in protein secretion into bile in young (4-week-old) rats. The amount of hepatic alpha-tubulin and the structure of the microtubular network were apparently not affected by MOCP. HRP (horseradish peroxidase) was used as a model protein, and its secretion into bile after administration through the jugular vein was measured. In adult (8-week-old) rats, two peaks of HRP output into bile were observed following administration: an early peak presumably due to paracellular transfer, and a late peak presumably due to transcytosis. In young rats (4 weeks old), the early peak was similar to that of adult animals, and was not affected by MOCP. However, the late peak was markedly smaller in young control rats, and was further reduced by MOCP. Brefeldin A decreased, whereas taurocholate did not change, the early peak, whereas both affected the transcytotic transport of HRP. Brefeldin A delayed HRP secretion (similarly in control and MOCP groups), without affecting cumulative output, whereas taurocholate accelerated the transcytotic transport of HRP in the control group, but not in the MOCP group. These results suggest that MOCP affects the maturation of hepatocyte mechanisms involved in the transcytotic secretion of HRP into bile. PMID:12769814

  20. COCAINE-ASSOCIATED ODOR CUE RE-EXPOSURE INCREASES BLOOD OXYGENATION LEVEL DEPENDENT SIGNAL IN MEMORY AND REWARD REGIONS OF THE MATERNAL RAT BRAIN*

    PubMed Central

    Caffrey, Martha K.; Febo, Marcelo

    2013-01-01

    BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and ?Cue). The BOLD response to +Cue and ?Cue was measured in dams on postpartum days 24. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus ?Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

  1. Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

    SciTech Connect

    Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

    1986-03-01

    Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development.

  2. Intrauterine Growth Restricted Rats Exercised at Pregnancy: Maternal-Fetal Repercussions.

    PubMed

    Corvino, S B; Netto, A O; Sinzato, Y K; Campos, K E; Calderon, I M P; Rudge, M V C; Volpato, G T; Zambrano, E; Damasceno, D C

    2015-08-01

    To evaluate the effect of swimming in pregnant rats born with intrauterine growth restriction (IUGR) and their offspring, IUGR rats were obtained using the streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic parental generation presented 10 rats and diabetic parental generation presented 116 rats. Of these, the mated nondiabetic female rats were 10 and the number of diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were classified as appropriate for pregnancy age, and 0 female was classified as large for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with appropriate (control [C]) and small (IUGR) weight for pregnancy age, respectively. At adult life, the C group was maintained as nonexercised C group and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia, impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels. Thus, swimming improved lipid metabolism and increased insulin sensitivity. However, the offspring showed retarded growth, reinforcing the need to stimulate the exercise practice in women under supervision with different professional expertise to promote appropriate gestational conditions and improve perinatal outcomes. PMID:25761405

  3. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning.

    PubMed

    Franco, J G; Fernandes, T P; Rocha, C P D; Calvio, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-11-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower ?3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases maternal body fat and this additional energy is transferred to the offspring during lactation, since at weaning the dams had normal fat and the pups were obese. The higher fat and protein concentrations in the breast milk seemed to induce early overnutrition in the HF offspring. In addition to storing energy as fat, the HF offspring had a larger reserve of glycogen and hyperglycaemia that may have resulted from increased gluconeogenesis. Hyperleptinaemia may stimulate both adrenal medullary and thyroid function, which may contribute to the development of cardiovascular diseases. These early changes induced by the maternal high-fat diet may contribute to development of metabolic syndrome. PMID:22869015

  4. Structural equation modeling and nested ANOVA: Effects of lead exposure on maternal and fetal growth in rats

    SciTech Connect

    Hamilton, J.D. ); O'Flaherty, E.J.; Shukla, R.; Gartside, P.S. ); Ross, R. )

    1994-01-01

    This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth. 24 refs., 4 figs., 6 tabs.

  5. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    SciTech Connect

    Leichter, J. )

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitum controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.

  6. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

    PubMed

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kgd) from gestational days (GD) 11 to 20, or 180 mg/kgd caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (?/?-glucoses, high density lipoprotein-cholesterol, ?-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. PMID:24463096

  7. Maternal dietary fat determines metabolic profile and the magnitude of endocannabinoid inhibition of the stress response in neonatal rat offspring.

    PubMed

    D'Asti, Esterina; Long, Hong; Tremblay-Mercier, Jennifer; Grajzer, Magdalena; Cunnane, Stephen C; Di Marzo, Vincenzo; Walker, Claire-Dominique

    2010-04-01

    Endocannabinoids (eCBs) are products of phospholipid (PL)-derived arachidonic acid (AA) that regulate hypothalamus-pituitary-adrenal axis activity. We hypothesized that differences in the quality and quantity of maternal dietary fat would modulate the PL AA content in the neonatal brain affecting stress responsiveness via differences in eCB production and activity in stress-activated brain areas. Pregnant rats were fed a 5% [control (C)] or 30% fat [high fat (HF)] diet rich in either n-6 (HF-n-6) or n-3 (HF-n-3) fat during the last week of gestation and lactation. Postnatal d 10 offspring were tested for metabolic hormones, AA (n-6) and eCB brain content, and hormonal effects of eCB receptor antagonism (AM251, 1 or 3 mg/kg ip) on stress responses. Like maternal diet, milk from HF-n-3 mothers had a reduced n-6/n-3 fat ratio compared with that of C and HF-n-6 mothers. Hypothalamic and hippocampal levels of PL AA were diet specific, reflecting the maternal milk and dietary n-6/n-3 ratio, with HF-n-3 offspring displaying reduced AA content relative to C and HF-n-6 offspring. Plasma corticosterone and insulin were elevated in HF-fed pups, whereas leptin was increased only in HF-n-6 pups. Basal eCB concentrations were also diet and brain region specific. In C pups, eCB receptor antagonist pretreatment increased stress-induced ACTH secretion, but not in the HF groups. Stress-induced corticosterone secretion was not sensitive to AM251 treatment in HF-n-3 pups. Thus, the nature of preweaning dietary fat differentially influences neonatal metabolic hormones, brain PL AA levels, and eCB, with functional consequences on hypothalamus-pituitary-adrenal axis modulation in developing rat pups. PMID:20160134

  8. Treatment with a monoclonal antibody against methamphetamine and amphetamine reduces maternal and fetal rat brain concentrations in late pregnancy.

    PubMed

    White, Sarah J; Hendrickson, Howard P; Atchley, William T; Laurenzana, Elizabeth M; Gentry, W Brooks; Williams, D Keith; Owens, S Michael

    2014-08-01

    We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ?15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP. PMID:24839971

  9. Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term

    SciTech Connect

    Morreale de Escobar, G.; Calvo, R.; Obregon, M.J.; Escobar Del Rey, F. )

    1990-05-01

    Normal dams were equilibrated isotopically with ({sup 125}I)T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their ({sup 125}I)T4 and T4 contents. The specific activity of the ({sup 125}I)T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the ({sup 125}I)T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered.

  10. Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams.

    PubMed

    McMurray, M S; Joyner, P W; Middleton, C W; Jarrett, T M; Elliott, D L; Black, M A; Hofler, V E; Walker, C H; Johns, J M

    2008-09-01

    Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocaine-treated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes. PMID:18609307

  11. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat

    PubMed Central

    Cerf, Marlon E.; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status. PMID:26742067

  12. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels.

    PubMed

    Ozolin, Terence R S; Weston, Andrea D; Perretta, Anthony; Thomson, Jason J; Brown, Nigel A

    2015-11-15

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40-100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. PMID:26375719

  13. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat.

    PubMed

    Cerf, Marlon E; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status. PMID:26742067

  14. 1,25(OH) sub 2 D sub 3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

    SciTech Connect

    Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. Institut National de la Sante et de la Recherche Medical )

    1988-04-01

    The autonomy and functional role of fetal 1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH){sub 2}D{sub 3} were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH){sub 2}D{sub 3} levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP{sub 9K} and CaBP{sub 28K}) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP{sub 9K} and CaBP{sub 28K} in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH){sub 2}D{sub 3} levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP{sub 9K} and renal CaBPs, but placental CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} tended to be lower, while renal CaBPs were normal; placental CaBP{sub 9K} was decreased. The results indicate that in the rat fetal 1,25(OH){sub 2}D{sub 3} depends on maternal 1,25(OH){sub 2}D{sub 3} or on factors regulating maternal 1,25(OH){sub 2}D{sub 3}. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH){sub 2}D{sub 3} levels confirms earlier data showing that 1,25(H){sub 2}D{sub 3} has a limited hormonal function during perinatal development in the rat.

  15. Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view

    PubMed Central

    Morgan, Timothy

    2014-01-01

    Since the late nineteenth century, protein restriction has been shown to improve hepatic encephalopathy. However, malnutrition has been described in up to 60 % of cirrhotic patients and is associated with increased mortality. Furthermore, emerging clinical evidence has revealed that a large proportion of cirrhotic patients may tolerate normal protein intake. However, approximately one third of cirrhotic patients with hepatic encephalopathy may need a short course of protein restriction, in addition to maximum medical therapy, to ameliorate the clinical course of their hepatic encephalopathy. For patients with chronic hepatic encephalopathy who are protein-sensitive, modifying their sources of nitrogen by using more vegetable protein, less animal protein, and branched-chain amino acids may improve their encephalopathy without further loss of lean body mass. In conclusion, among cirrhotics with hepatic encephalopathy, modulation of normal protein intake must take into account the patients hepatic reserve, severity of hepatic encephalopathy, and current nutritional status. PMID:25525477

  16. Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

    PubMed Central

    Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

    2014-01-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP dietexposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP dietfed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor substrate-1, and AS160 phosphorylation and impaired glucose transporter type 4 translocation. PMID:24797633

  17. Continuous central infusion of cannabinoid receptor agonist WIN 55,212-2 decreases maternal care in lactating rats: consequences for fear conditioning in adulthood males.

    PubMed

    Costa, Helosa Helena Vilela; Vilela, Fabiana Cardoso; Giusti-Paiva, Alexandre

    2013-11-15

    In lactating rats, maternal behavior consists of several integrated elements designed to promote care and nutrition of the offspring to ensure their survival. Given previous studies showing the role of the brain endocannabinoid system in maternal behavior, the objective of this work was to determine which changes in maternal care occur during continuous intracerebroventricular infusion of a cannabinoid receptor agonist (WIN 55,212-2). Maternal behavior was scored daily in 4 sessions of 72 min each (3 during the light phase and 1 during the dark phase). During drug infusion, the results indicated decreased time spent by the mother licking pups and an increase in feeding time. To determine the extent to which variations in maternal care during the neonatal period affect offspring later in life, we evaluated possible changes in the fear response of offspring once they reached adulthood. Offspring of mothers treated with a cannabinoid agonist presented a lower latency for freezing behavior and increased time spent freezing in a fear test. These results show that treatment with a cannabinoid agonist decreases maternal care, mainly licking, in lactating rats and is associated with increased fear responses in offspring later in life. PMID:24060654

  18. Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect.

    PubMed

    Chen, Hui-Feng; Su, Hui-Min

    2012-03-01

    Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet. PMID:21543216

  19. Prevention of maternal and developmental toxicity in rats via dietary inclusion of common aflatoxin sorbents: potential for hidden risks.

    PubMed

    Mayura, K; Abdel-Wahhab, M A; McKenzie, K S; Sarr, A B; Edwards, J F; Naguib, K; Phillips, T D

    1998-02-01

    In earlier work, we have reported that a phyllosilicate clay (HSCAS or NovaSil) can tightly and selectively bind the aflatoxins in vitro and in vivo. Since then, a variety of untested clay and zeolitic minerals have been added to poultry and livestock feeds as potential "aflatoxin binders." However, the efficacy and safety of these products have not been determined. A common zeolite that has been frequently added to animal feed is clinoptilolite. Our objectives in this study were twofold: (1) to utilize the pregnant rat as an in vivo model to compare the potential of HSCAS and clinoptilolite to prevent the developmental toxicity of aflatoxin B1 (AfB1), and (2) to determine the effect of these two sorbents on the metabolism and bioavailability of AfB1. Clay and zeolitic minerals (HSCAS or clinoptilolite) were added to the diet at a level of 0.5% (w/w) and fed to pregnant Sprague-Dawley rats throughout pregnancy (i.e., day 0 to 20). Treatment groups (HSCAS or clinoptilolite) alone and in combination with AfB1 were exposed to sorbents in the feed as well as by gavage. Untreated and AfB1 control animals were fed the basal diet without added sorbent. Between gestation days 6 and 13, animals maintained on diets containing sorbent were gavaged with corn oil in combination with an amount of the respective sorbent equivalent to 0.5% of the estimated maximum daily intake of feed. Animals receiving AfB1 were dosed orally (between days 6 and 13) with AfB1 (2 mg/kg body wt) either alone or concomitantly with a similar quantity of the respective sorbent. Evaluations of toxicity were performed on day 20. These included: maternal (mortality, body weights, feed intake, and litter weights), developmental (embryonic resorptions and fetal body weights), and histological (maternal livers and kidneys). Sorbents alone were not toxic; AfB1 alone and with clinoptilolite resulted in significant maternal and developmental toxicity. Animals treated with HSCAS (plus AfB1) were comparable to controls. Importantly, clinoptilolite (plus AfB1) resulted in severe maternal liver lesions (more severe than AfB1 alone), suggesting that this zeolite may interact with dietary components that modulate aflatoxicosis. In metabolism studies, adult male Sprague-Dawley rats, maintained on diets containing 0.5% (w/w) HSCAS or clinoptilolite, were dosed orally with 2.0 mg AfB1/kg body wt. The concentration of the major urinary metabolite (AfM1) was considerably decreased in the presence of HSCAS. These results suggest that the mechanism of protection of AfB1-induced maternal and developmental toxicities in the rat may involve adsorption and reduction of AfB1 bioavailability in vivo. Importantly, this study demonstrates the potential for significant hidden risks associated with the inclusion of nonselective aflatoxin binders in feeds. Aflatoxin sorbents should be rigorously tested individually and thoroughly characterized in vivo, paying particular attention to their effectiveness and safety in sensitive animal models and their potential for deleterious interactions. PMID:9520353

  20. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosi...

  1. Vasopressin V1a, but not V1b, receptors within the PVN of lactating rats mediate maternal care and anxiety-related behaviour.

    PubMed

    Bayerl, Doris S; Hönig, Jennifer N; Bosch, Oliver J

    2016-05-15

    The brain neuropeptide arginine-vasopressin (AVP) mediates a wide range of social behaviours via its V1a (V1aR) but also its V1b receptor (V1bR). With respect to maternal behaviour, V1bR are still less investigated, whereas V1aR have been shown repeatedly to trigger maternal behaviour, depending on the brain region. Here, we aimed to study the role of both V1aR and V1bR within the hypothalamic paraventricular nucleus (PVN), a major source of AVP, in maternal care (lactation day (LD) 1), maternal motivation in the pup retrieval test (LD 3) and anxiety-related behaviour on the elevated plus maze (EPM; LD 5) by acute local infusion of receptor subtype-specific antagonists for V1aR (d(CH2)5Tyr(Me)(2)AVP) or V1bR (SSR149415). Furthermore, we compared V1bR expression in the PVN of virgin versus lactating rats (LD 4). Our results demonstrate that within the PVN neither V1bR mRNA (qPCR) nor protein (Western Blot) content differed between virgin and lactating rats. Regarding behaviour, acute antagonism of V1aR, but not of V1bR, decreased the occurrence of nursing as well as anxiety-related behaviour as reflected by higher percentage of time spent on and of entries into the open arms of the EPM. Maternal motivation was not affected by any treatment. In summary, we demonstrate subtype-specific involvement of V1 receptors within the PVN in mediating various maternal behaviours. The lack of effects after V1bR blockade reveals that AVP acts mainly via V1aR in the PVN, at least in lactating rats, to mediate maternal care and anxiety. PMID:26909846

  2. Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats

    PubMed Central

    Mela, Virginia; Díaz, Francisca; Borcel, Erika; Argente, Jesús; Chowen, Julie A.; Viveros, Maria-Paz

    2015-01-01

    Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect. PMID:26382238

  3. Heightened fear in response to a safety cue and extinguished fear cue in a rat model of maternal immune activation.

    PubMed

    Sangha, Susan; Greba, Quentin; Robinson, Paul D; Ballendine, Stephanie A; Howland, John G

    2014-01-01

    Maternal immune activation (MIA) during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia and autism in the offspring. Hence, changes in an array of behaviors, including behavioral flexibility, consistent with altered functioning of cortico-limbic circuits have been reported in rodent models of MIA. Surprisingly, previous studies have not examined the effect of MIA on the extinction of fear conditioning which depends on cortico-limbic circuits. Thus, we tested the effects of treating pregnant Long Evans rats with the viral mimetic polyI:C (gestational day 15; 4 mg/kg; i.v.) on fear conditioning and extinction in the male offspring using two different tasks. In the first experiment, we observed no effect of polyI:C treatment on the acquisition or extinction of a classically conditioned fear memory in a non-discriminative auditory cue paradigm. However, polyI:C-treated offspring did increase contextual freezing during the recall of fear extinction in this non-discriminative paradigm. The second experiment utilized a recently developed task to explicitly test the ability of rats to discriminate among cues signifying fear, reward, and safety; a task that requires behavioral flexibility. To our surprise, polyI:C-treated rats acquired the task in a manner similar to saline-treated rats. However, upon subsequent extinction training, they showed significantly faster extinction of the freezing response to the fear cue. In contrast, during the extinction recall test, polyI:C-treated offspring showed enhanced freezing behavior before and after presentation of the fear cue, suggesting an impairment in their ability to regulate fear behavior. These behavioral results are integrated into the literature suggesting impairments in cortico-limbic brain function in the offspring of rats treated with polyI:C during pregnancy. PMID:24847231

  4. Heightened fear in response to a safety cue and extinguished fear cue in a rat model of maternal immune activation

    PubMed Central

    Sangha, Susan; Greba, Quentin; Robinson, Paul D.; Ballendine, Stephanie A.; Howland, John G.

    2014-01-01

    Maternal immune activation (MIA) during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia and autism in the offspring. Hence, changes in an array of behaviors, including behavioral flexibility, consistent with altered functioning of cortico-limbic circuits have been reported in rodent models of MIA. Surprisingly, previous studies have not examined the effect of MIA on the extinction of fear conditioning which depends on cortico-limbic circuits. Thus, we tested the effects of treating pregnant Long Evans rats with the viral mimetic polyI:C (gestational day 15; 4 mg/kg; i.v.) on fear conditioning and extinction in the male offspring using two different tasks. In the first experiment, we observed no effect of polyI:C treatment on the acquisition or extinction of a classically conditioned fear memory in a non-discriminative auditory cue paradigm. However, polyI:C-treated offspring did increase contextual freezing during the recall of fear extinction in this non-discriminative paradigm. The second experiment utilized a recently developed task to explicitly test the ability of rats to discriminate among cues signifying fear, reward, and safety; a task that requires behavioral flexibility. To our surprise, polyI:C-treated rats acquired the task in a manner similar to saline-treated rats. However, upon subsequent extinction training, they showed significantly faster extinction of the freezing response to the fear cue. In contrast, during the extinction recall test, polyI:C-treated offspring showed enhanced freezing behavior before and after presentation of the fear cue, suggesting an impairment in their ability to regulate fear behavior. These behavioral results are integrated into the literature suggesting impairments in cortico-limbic brain function in the offspring of rats treated with polyI:C during pregnancy. PMID:24847231

  5. Central neural responses to restraint stress are altered in rats with an early life history of repeated brief maternal separation

    PubMed Central

    Banihashemi, Layla; O’Neill, Elizabeth J.; Rinaman, Linda

    2011-01-01

    Repeated brief maternal separation (i.e., 15 minutes daily, MS15) of rat pups during the first one to two postnatal weeks enhances active maternal care received by the pups and attenuates their later behavioral and neuroendocrine responses to stress. In previous work, we found that MS15 also alters the developmental assembly and later structure of central neural circuits that control autonomic outflow to the viscera, suggesting that MS15 may alter central visceral circuit responses to stress. To examine this, juvenile rats with a developmental history of either MS15 or no separation (NS) received microinjection of retrograde neural tracer, FluoroGold (FG), into the hindbrain dorsal vagal complex (DVC). After one week, FG-injected rats and surgically intact littermates were exposed to either a 15-minute restraint stress or an unrestrained control condition, and then perfused one hour later. Brain tissue sections from surgically-intact littermates were processed for Fos alone or in combination with phenotypic markers to examine stress-induced activation of neurons within the paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), and hindbrain DVC. Compared to NS controls, MS15 rats displayed less restraint-induced Fos activation within the dorsolateral BNST (dBNST), the caudal PVN, and noradrenergic neurons within the caudal DVC. To examine whether these differences corresponded with altered neural inputs to the DVC, sections from tracer-injected rats were double-labeled for FG and Fos to quantify retrogradely-labeled neurons within hypothalamic and limbic forebrain regions of interest, and the proportion of these neurons activated after restraint. Only the dBNST displayed a significant effect of postnatal experience on restraint-induced Fos activation of DVC-projecting neurons. The distinct regional effects of MS15 on stress-induced recruitment of neurons within hypothalamic, limbic forebrain, and hindbrain regions has interesting implications for understanding how early life experience shapes the functional organization of stress-responsive circuits. PMID:21736922

  6. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism.

    PubMed

    Klampfl, Stefanie M; Brunton, Paula J; Bayerl, Doris S; Bosch, Oliver J

    2016-02-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  7. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  8. Influence of Maternal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Socioemotional Behaviors in Offspring Rats

    PubMed Central

    Nguyen, Anh T.N.; Nishijo, Muneko; Hori, Etsuro; Nguyen, Nui M.; Pham, Tai T.; Fukunaga, Kohji; Nakagawa, Hideaki; Tran, Anh H.; Nishijo, Hisao

    2013-01-01

    Effects of dioxins on cognitive functions were reported in previous studies conducted in humans and animals. In the present study, we investigated the influence of dioxin exposure during pregnancy on social interaction and on the activity of offspring, which are related to neurodevelopmental disturbances. In addition, we analyzed neurochemical alterations of the limbic system of rat brains to suggest one mechanism of dioxin effects on brain function. We believe that this manuscript is suitable for publication in Environmental Health Insights because it provides an interesting topic for a wide global audience. To clarify the relationships between maternal dioxin exposure and socioemotional functions of rat offspring, dams were given TCDD (1.0 ?g/kg) on gestational day 15. Social interactions and forced swimming time were compared between TCDD-exposed and control offspring in each gender. Frequency and duration of locomotion were higher, and durations per one behavior of proximity and social contact were significantly lower in the exposed males, while only the duration of proximity was lower in the exposed females. Forced swimming time on the first day was significantly longer in the exposed males. In the limbic system of the rat brain, the levels and/or activity of CaMKII? were decreased in males and were increased in females in the exposed offspring. These results suggest that prenatal TCDD exposure induces hyperactivity and socioemotional deficits, particularly in the male offspring due to alterations in CaMKII? activity in the limbic system of the brain. PMID:23493046

  9. Long-term consequences of early maternal deprivation in serotonergic activity and HPA function in adult rat.

    PubMed

    Rentesi, Georgia; Antoniou, Katerina; Marselos, Marios; Fotopoulos, Andreas; Alboycharali, Jihad; Konstandi, Maria

    2010-08-01

    Increasing body of evidence indicates that early life stressful events may induce permanent alterations in neurodevelopment, which in turn, could lead to the development of psychopathologies in adulthood. In particular, maternal deprivation (MD) for 24h in rats has been associated with several abnormalities in brain and behaviour during adulthood, relevant to the neurobiological substrate of anxiety disorders. The aim of the present study was to clarify the long-term effects of MD, on hypothalamo-pituitary-adrenal (HPA) axis activity and serotonergic (5-HT) function, in adulthood, subjects that have not been yet thoroughly investigated. For this purpose, Wistar rat pups were deprived from their mothers for a 24-h single period at postnatal day 9 (pnd 9) and were examined when aged 69-90 days. Plasma corticosterone and ACTH levels along with the animal's behaviour in an open field were used as indices of stress. Moreover, serotonergic activity was estimated in hypothalamus and hippocampus, key structures in the coordination of neuroendocrine and behavioural responses to stress. Interestingly, in adulthood, MD rats compared to controls, displayed decreased body weight, increased serotonergic activity and "anxiety" related behaviour, as well as elevated plasma corticosterone and ACTH levels. The findings of this study showed that MD results in long-term modifications in HPA axis and serotonergic activity indicating a clear relationship between early life stressful events and the development of anxiety-like disorders later in adulthood. PMID:20435091

  10. RAT PLACENTATION: AN EXPERIMENTAL MODEL FOR INVESTIGATING THE HEMOCHORIAL MATERNAL-FETAL INTERFACE

    PubMed Central

    Soares, Michael J.; Chakraborty, Damayanti; Rumi, M.A. Karim; Konno, Toshihiro; Renaud, Stephen J.

    2011-01-01

    The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat to the forefront in placentation research. PMID:22284666

  11. FETAL ANEMIA FOLLOWING MATERNAL EXPOSURE TO 5-FLUOROURACIL IN THE RAT

    EPA Science Inventory

    This study examined dose-dependent changes in fetal hematology after maternal 5-FU exposure (0, 20, 30, 40 mg/kg on GD14) to assess 1) hematopoiesis as a potential target for its developmental toxicity, and 2) the significance of the resultant fetal anemia to developmental outcom...

  12. MATERNAL HEPATIC EFFECTS OF 1,2,4,5-TETRACHLOROBENZENE IN THE RAT

    EPA Science Inventory

    1,2,4,5-Tetrachlorobenzene (TCB) is an industrial intermediate used in the production of 2,4,5-trichlorophenoxyacetic acid. This herbicide contains trace quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Because of possible maternal hepatic or reproductive effects of this...

  13. Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal obesity at conception increases the risk of offspring obesity, thus propagating an intergenerational vicious cycle. Male offspring born to obese dams are hyper-responsive to high fat diets, gaining greater body weight, fat mass and additional metabolic sequelae compared to lean controls. ...

  14. Effect of maternal obesity on fetal bone development in the rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

  15. Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

    PubMed Central

    Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser

    2014-01-01

    Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “detrimental” effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “substitute” mother. The maternal care of biological and “substitute” mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the “substitute” mother did not exhibit overt maltreatment. A mixture of “detrimental” and “beneficial” effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may “buffer” the effects of ELS in a context-dependent manner. PMID:24616673

  16. Gestational Ethanol and Nicotine Exposure: Effects on Maternal Behavior, Oxytocin, and Offspring Ethanol Intake in the Rat

    PubMed Central

    McMurray, M.S.; Williams, S.K.; Jarrett, T.M.; Cox, E.T.; Fay, E.E.; Overstreet, D.H.; Walker, C.H.; Johns, J.M.

    2008-01-01

    Alcohol consumption and smoking during pregnancy is common, despite the known adverse effects of these drugs on fetal development. Though studies on the effects of each drug separately are published, little is known about the effect of concurrent use of alcohol and nicotine in humans or in preclinical models. In this report, we examined the impact of continuous gestational exposure to both ethanol via liquid diet and nicotine via an osmotic minipump on maternal behavior, offspring ethanol intake, and oxytocin levels in a rat model. Dams were tested for the onset of maternal behavior with litters of unexposed surrogate pups and then killed to examine oxytocin levels within specific brain regions. Drug-exposed offspring reared by surrogate dams were tested for ethanol intake at either adolescence or adulthood, and oxytocin levels were measured in relevant brain regions after behavioral tests. Dams exhibited minor deficits in maternal care, which were associated with lower oxytocin levels in both the ventral tegmental and medial preoptic areas compared to control dams. Prenatal exposure altered sex-specific ethanol intake, with differential effects at adolescence and adulthood. Oxytocin system changes were also apparent in the ventral tegmental and medial preoptic regions of drug-exposed adolescent and adult offspring. These results suggest that dam treatment with ethanol and nicotine can somewhat negatively affect the early rearing environment, and that prenatal exposure to both of these drugs results in drinking behavior differing from what would be expected from either drug alone. Oxytocins possible involvement in the mediation of these effects is highlighted. PMID:18664381

  17. Gestational ethanol and nicotine exposure: effects on maternal behavior, oxytocin, and offspring ethanol intake in the rat.

    PubMed

    McMurray, M S; Williams, S K; Jarrett, T M; Cox, E T; Fay, E E; Overstreet, D H; Walker, C H; Johns, J M

    2008-01-01

    Alcohol consumption and smoking during pregnancy is common, despite the known adverse effects of these drugs on fetal development. Though studies on the effects of each drug separately are published, little is known about the effect of concurrent use of alcohol and nicotine in humans or in preclinical models. In this report, we examined the impact of continuous gestational exposure to both ethanol via liquid diet and nicotine via an osmotic minipump on maternal behavior, offspring ethanol intake, and oxytocin levels in a rat model. Dams were tested for the onset of maternal behavior with litters of unexposed surrogate pups and then killed to examine oxytocin levels within specific brain regions. Drug-exposed offspring reared by surrogate dams were tested for ethanol intake at either adolescence or adulthood, and oxytocin levels were measured in relevant brain regions after behavioral tests. Dams exhibited minor deficits in maternal care, which were associated with lower oxytocin levels in both the ventral tegmental and medial preoptic areas compared to control dams. Prenatal exposure altered sex-specific ethanol intake, with differential effects at adolescence and adulthood. Oxytocin system changes were also apparent in the ventral tegmental and medial preoptic regions of drug-exposed adolescent and adult offspring. These results suggest that dam treatment with ethanol and nicotine can somewhat negatively affect the early rearing environment, and that prenatal exposure to both of these drugs results in drinking behavior differing from what would be expected from either drug alone. Oxytocin's possible involvement in the mediation of these effects is highlighted. PMID:18664381

  18. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats.

    PubMed

    Hallam, Megan C; Reimer, Raylene A

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  19. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C.

    PubMed

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  20. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

    PubMed Central

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  1. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    PubMed Central

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  2. FETAL AND MATERNAL EFFECTS OF CONTINUAL EXPOSURE OF RATS TO 970-MHZ CIRCULARLY-POLARIZED MICROWAVES

    EPA Science Inventory

    Virtually continual exposure to 970-MHz microwaves in circularly-polarized waveguides was used to elicit fetal responses in Sprague-Dawley rats during gestation. wo hundred fifty rats were exposed to microwave radiation at whole-body averaged specific absorption rates (SAR) of 0....

  3. SENSITIVITY OF FETAL RAT TESTICULAR STEROIDOGENESIS TO MATERNAL PROCHLORAZ EXPOSURE AND THE UNDERLYING MECHANISM OF INHIBITION

    EPA Science Inventory

    Since prochloraz (PCZ) is an imidazole fungicide that inhibits gonadal steroidogenesis and antagonizes the androgen receptor (AR), we hypothesized that pubertal exposure to PCZ would delay male rat reproductive development. Sprague Dawley rats were dosed by gavage with 0, 31.3, ...

  4. A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation.

    PubMed

    Rus, Gislaine Z; Carlessi, Anelise S; Titus, Stephanie E; Abelaira, Helena M; Igncio, Zuleide M; da Luz, Jaine R; Matias, Beatriz I; Bruchchen, Livia; Florentino, Drielly; Vieira, Andriele; Petronilho, Fabricia; Quevedo, Joo

    2015-11-01

    Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived?+?saline; nondeprived?+?S-ketamine (15 mg/kg); deprived?+?saline; deprived?+?S-ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive-like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive-like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long-term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long-term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1268-1281, 2015. PMID:25728399

  5. Oxytocin mediates the acquisition of filial, odor-guided huddling for maternally-associated odor in preweanling rats

    PubMed Central

    Kojima, Sayuri; Alberts, Jeffrey R.

    2011-01-01

    The present study was designed to examine possible roles of oxytocin (OT) in the acquisition of a filial huddling preference in preweanling rats. We used a procedure in which a scented, foster mother can induce an odor-guided huddling preference in preweanling pups, following a single, 2-h-long co-habitation (Kojima & Alberts, 2009, 2011). This single, discrete period for preference learning enables us to observe the mother-pup interactions that establish the pups’ preferences and to intervene with experimental manipulations. Four, 14-day-old littermates interacted with a scented foster mother that provided maternal care during a 2-h session. Two of the pups were pretreated with an intracerebroventricular injection of OT or an oxytocin antagonist (OTA), and the others received a vehicle injection. Filial preference for a maternally-paired odor was measured in a huddling test the next day. OT is necessary for acquisition of the filial preference: Odor learning was blocked in the pups treated with OTA, but not in their vehicle-treated littermates who experienced the same mother at the same time. Injection with exogenous OT did not augment the pups’ preference. Manipulating pups’ central OT also altered the contact interactions of the mother and pups. When some pups received OT, mother-litter aggregations formed as frequently and with similar combinations of bodies, but contact aggregations were significantly more cohesive than when some pups in the litter received OTA. We discuss dual, behavioral and neuroendocrine roles of OT in social learning by preweanling rats. PMID:21872599

  6. Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex

    PubMed Central

    de Souza, Daniela F.; Wartchow, Krista M.; Lunardi, Paula S.; Brolese, Giovana; Tortorelli, Lucas S.; Batassini, Cristiane; Biasibetti, Regina; Gonçalves, Carlos-Alberto

    2015-01-01

    Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders. PMID:26733814

  7. Effects of early maternal separation on biobehavioral and neuropathological markers of Alzheimer's disease in adult male rats.

    PubMed

    Martisova, Eva; Aisa, Brbara; Guereu, Gorka; Ramrez, Mara Javier

    2013-05-01

    Stress has been described as a risk factor for the development of Alzheimers disease (AD). In the present work we aim to study the validity of an experimental model of neonatal chronic stress in order to recapitulate the main hallmarks of AD. Male Wistar rats that were separated daily from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood cognitive deficits novel object recognition test. In the hippocampus of MS rats, increases in both A?40 and A?42 levels, the principal constituent of amyloid plaques observed in AD, were accompanied by increased expression of the cleaving enzyme BACE1. Hyperphosphorylation of Tau associated to increased activation of the tau kinase JNK1 was also found. Decreased cell number in the hippocampus was observed in stressed rats, as a consequence of both decreased cell proliferation and increased apoptotic death. Decreases in BDNF and in the synaptic markers synaptophysin and PSD-95 were also found in MS rats. All these effects could be related to an HPA axis hyperactivity, as reflected in significant increases in corticosterone levels and decreases in glucocorticoid receptor expression. Further, SHSY5Y neuroblastoma cells treated with corticosterone showed increased BACE1, pTau and pJNK1 expression. In addition, venlafaxine, an antidepressant able to modulate HPA axis activity, reversed all the above cited deleterious effects of chronic stress, both in vivo and in vitro. It is proposed that the MS model can be considered as an appropriate experimental model for the study of sporadic AD. PMID:23305081

  8. Brain–blood amino acid correlates following protein restriction in murine maple syrup urine disease

    PubMed Central

    2014-01-01

    Background Conventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain. Methods To address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses. Results LEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 μM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU. Conclusions Our results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders. PMID:24886632

  9. Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty.

    PubMed

    Veerawatananan, Bovorn; Surakul, Pornprom; Chutabhakdikul, Nuanchan

    2016-06-01

    The GABAergic synapse undergoes structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in the pup's brain that are associated with the pathophysiology of neuropsychiatric disorders in adults; however, the mechanism for this is still unclear. In this study, we examined the effects of maternal restraint stress on the development of Cation-Chloride Cotransporters (CCCs) and the GABAA receptor α1 and α5 subunits in the hippocampus of rat pups at different postnatal ages. Our results demonstrate that maternal restraint stress induces a transient but significant increase in the level of NKCC1 (Sodium-Potassium Chloride Cotransporter 1) only at P14, followed by a brief, yet significant increase in the level of KCC2 (Potassium-Chloride Cotransporter 2) at P21, which then decreases from P28 until P40. Thus, maternal stress alters NKCC1 and KCC2 ratio in the hippocampus of rat pups, especially during P14 to P28. Maternal restraint stress also caused biphasic changes in the level of GABAA receptor subunits in the pup's hippocampus. GABAA receptor α1 subunit gradually increased at P14 then decreased thereafter. On the contrary, GABAA receptor α5 subunit showed a transient decrease followed by a long-term increase from P21 until P40. Altogether, our study suggested that the maternal restraint stress might delay maturation of the GABAergic system by altering the expression of NKCC1, KCC2 and GABAA receptor α1 and α5 subunits in the hippocampus of rat pups. These changes demonstrate the dysregulation of inhibitory neurotransmission during early life, which may underlie the pathogenesis of psychiatric diseases at adolescence. PMID:26844244

  10. Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty

    PubMed Central

    Veerawatananan, Bovorn; Surakul, Pornprom; Chutabhakdikul, Nuanchan

    2015-01-01

    The GABAergic synapse undergoes structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in the pup's brain that are associated with the pathophysiology of neuropsychiatric disorders in adults; however, the mechanism for this is still unclear. In this study, we examined the effects of maternal restraint stress on the development of Cation-Chloride Cotransporters (CCCs) and the GABAA receptor α1 and α5 subunits in the hippocampus of rat pups at different postnatal ages. Our results demonstrate that maternal restraint stress induces a transient but significant increase in the level of NKCC1 (Sodium–Potassium Chloride Cotransporter 1) only at P14, followed by a brief, yet significant increase in the level of KCC2 (Potassium-Chloride Cotransporter 2) at P21, which then decreases from P28 until P40. Thus, maternal stress alters NKCC1 and KCC2 ratio in the hippocampus of rat pups, especially during P14 to P28. Maternal restraint stress also caused biphasic changes in the level of GABAA receptor subunits in the pup's hippocampus. GABAA receptor α1 subunit gradually increased at P14 then decreased thereafter. On the contrary, GABAA receptor α5 subunit showed a transient decrease followed by a long-term increase from P21 until P40. Altogether, our study suggested that the maternal restraint stress might delay maturation of the GABAergic system by altering the expression of NKCC1, KCC2 and GABAA receptor α1 and α5 subunits in the hippocampus of rat pups. These changes demonstrate the dysregulation of inhibitory neurotransmission during early life, which may underlie the pathogenesis of psychiatric diseases at adolescence. PMID:26844244

  11. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

    PubMed

    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation. PMID:26989972

  12. Maternal serum omentin-1 profile is similar in humans and in the rat animal model.

    PubMed

    Garcs, Mara F; Ruz-Linares, Carlos E; Vallejo, Sergio A; Peralta, Jhon J; Sanchez, Elizabeth; Ortiz-Rovira, Alexsandra; Curtidor, Yurani; Parra, Mario O; Leal, Luis G; Alzate, Juan P; Acosta, Bernarda Jineth; Diguez, Carlos; Nogueiras, Rubn; Caminos, Jorge E

    2015-09-01

    Omentin-1 is an adipocytokine with anti-inflammatory activity that has been associated with different metabolic disorders. The aim of this study is to investigate the serum profiles of omentin-1 throughout human and rat pregnancy. Serum omentin-1 levels were determined by ELISA in a prospective cohort study of healthy pregnant women (n=40) during the three trimesters of pregnancy and in twenty healthy non-pregnant women during the follicular and luteal phase of the menstrual cycle. In addition, serum omentin-1 levels were measured in rats during different periods of pregnancy (gestational days 8, 12, 16, 19, and 21) and in an age-matched control (virgin) group of rats (n=12rats/group). Finally, immunohistochemistry was used to demonstrate the presence of omentin-1 protein in human and rat placenta. Omentin-1 immunoreactivity was detected in cytotrophoblasts, syncytiotrophoblasts, sparse Hofbauer cells, and endothelial cells of the stem villi of human placenta. Additionally, it was detected in the labyrinthine trophoblast and yolk sac layer of the rat placenta. Human and rat serum omentin-1 levels were significantly lower in the late gestational period when compared with the non-pregnant women and virgin rats (p<0.05). Serum omentin-1 changes were not significant throughout the gestation in both species (p>0.05). Human serum omentin-1 levels have an inverse relationship with triglyceride levels during pregnancy. Our findings have not determined the exact role of omentin-1 during pregnancy, concerning the metabolic control of triglycerides and other energy sources. Whether omentin-1 decrease implies a regulatory function is still not clear. Further studies are needed to address this issue and determine the role of omentin-1 in metabolic adaptations during normal human and rat pregnancy. PMID:26144294

  13. Effect of Maternal Probiotic Intervention on HPA Axis, Immunity and Gut Microbiota in a Rat Model of Irritable Bowel Syndrome

    PubMed Central

    Barouei, Javad; Moussavi, Mahta; Hodgson, Deborah M.

    2012-01-01

    Objective To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS) and/or restraint stress in adulthood (AS) in Wistar rats. Design Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3×109 CFU/mL) and Propionibacterium jensenii 702 (8.0×108 CFU/mL) from 10 days before conception until postnatal day (PND) 22 (weaning day), or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. Results Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. Conclusion Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the immune environment of stressed animals and protected, in part, against stress-induced disturbances in adult gut microflora. PMID:23071537

  14. Novel insights about the mechanism of visceral hypersensitivity in maternally separated rats.

    PubMed

    Bian, Z X

    2012-07-01

    Visceral hypersensitivity (VHS) is one of the most important characteristics of functional gastrointestinal disorders, including irritable bowel syndrome (IBS). Stress, whether physical or psychological, is known to be a crucial factor for inducing and maintaining visceral sensitivity in humans and rodents, but how stress induces VHS is not fully understood. In a recent study published in Neurogastroenterology and Motility, Wouters et al. demonstrate, for the first time, that maternal separation induces activation of periaqueductal gray (PAG), the hippocampus and the somatosensory cortex concomitantly with increased deactivation of the pre-frontal cortex. The findings provide insight on the role of maternal separation in inducing regional cerebral blood flow changes and cerebral plasticity. These novel insights on the role of central activation in the modulation of stress-induced VHS add to our growing understanding of the mechanisms that underlie VHS and suggest potential new drug development targets in stress-related diseases, including IBS. PMID:22709237

  15. Paralemniscal TIP39 is induced in rat dams and may participate in maternal functions

    PubMed Central

    Varga, Tams; Mogyordi, Bence; Bag, Attila G.; Cservenk, Melinda; Domokos, Dominika; Renner, va; Gallatz, Katalin; Usdin, Ted B.; Palkovits, Mikls

    2011-01-01

    The paralemniscal area, situated between the pontine reticular formation and the lateral lemniscus in the pontomesencephalic tegmentum contains some tuberoin-fundibular peptide of 39 residues (TIP39)-expressing neurons. In the present study, we measured a 4 times increase in the level of TIP39 mRNA in the paralemniscal area of lactating mothers as opposed to nulliparous females and mothers deprived of pups using real-time RT-PCR. In situ hybridization histochemistry and immunolabeling demonstrated that the induction of TIP39 in mothers takes place within the medial paralemniscal nucleus, a cytoarchitectonically distinct part of the paralemniscal area, and that the increase in TIP39 mRNA levels translates into elevated peptide levels in dams. The paralemniscal area has been implicated in maternal control as well as in pain perception. To establish the function of induced TIP39, we investigated the activation of TIP39 neurons in response to pup exposure as maternal, and formalin injection as noxious stimulus. Both stimuli elicited c-fos expression in the paralemniscal area. Subsequent double labeling demonstrated that 95% of neurons expressing Fos in response to pup exposure also contained TIP39 immunoreactivity and 91% of TIP39 neurons showed c-fos activation by pup exposure. In contrast, formalin-induced Fos does not co-localize with TIP39. Instead, most formalin-activated neurons are situated medial to the TIP39 cell group. Our data indicate that paralemniscal neurons may be involved in the processing of maternal and nociceptive information. However, two different groups of paralemniscal neurons participate in the two functions. In particular, TIP39 neurons may participate in the control of maternal functions. PMID:22081168

  16. Brief maternal deprivation of rats reduces hepatic mixed function oxidase activities

    SciTech Connect

    Vesell, E.S. ); Heubel, F.; Netter, K.J. )

    1989-01-01

    Deprivation of pups from mother and sibs for 3 min daily from day 5 today 41 of life reduced activities of 4 hepatic mixed function oxidases (MFO) expressed per mg protein in male rats compared to unhandled control rats. These decreases, though generally small, 22.4% and under, reached statistical significance for the substrates aminopyrine, benzphetamine and ethoxycoumarin. This handling procedure did not consistently affect the inductive response to phenobarbital. Previously ignored as a source of variability in response to xenobiotics, handling appears from these results to merit further investigation as such a factor in uninduced rats. Differences among rats in handling could contribute to large day-to-day variations in their metabolism of xenobiotics.

  17. EFFECTS ON THE FETUS OF MATERNAL BENOMYL EXPOSURE IN THE PROTEIN-DEPRIVED RAT

    EPA Science Inventory

    The separate and combined effects of protein deprivation and benomyl ((methyl 1-butylcarbomoyl)2-benzimidazole carbamate) exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups...

  18. Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat

    PubMed Central

    Farrar, Andrew M.; Hockemeyer, Jrg; Mller, Christa E.; Salamone, John D.; Morrell, Joan I.

    2011-01-01

    Rationale Mesolimbic dopamine (DA), particularly in the nucleus accumbens, importantly regulates activational aspects of maternal responsiveness. DA antagonism and accumbens DA depletions interfere with early postpartum maternal motivation by selectively affecting most forms of active maternal behaviors, while leaving nursing behavior relatively intact. Considerable evidence indicates that there is a functional interaction between DA D2 and adenosine A2A receptors in striatal areas, including the nucleus accumbens. Objective This study was conducted to determine if adenosine A2A receptor antagonism could reverse the effects of DA receptor antagonism on early postpartum maternal behavior. Methods The adenosine A2A receptor antagonist MSX-3 (0.252.0 mg/kg, IP) was investigated for its ability to reverse the effects of the DA D2 receptor antagonist haloperidol (0.1 mg/kg, IP) on the maternal behavior of early postpartum female rats. Results Haloperidol severely impaired the expression of active maternal components, including retrieval and grouping the pups at the nest site, pup licking, and nest building. Co-administration of MSX-3 (0.252.0 mg/kg, IP) with haloperidol produced a dose-related attenuation of the haloperidol-induced behavioral deficits in early postpartum females. Doses of MSX-3 that effectively reversed the effects of haloperidol (0.5, 1.0 mg/kg), when administered in the absence of haloperidol, did not affect maternal responding or locomotor activity. Conclusions Adenosine and DA systems interact to regulate early postpartum maternal responsiveness. This research may potentially contribute to the development of strategies for treatments of psychiatric disorders during the postpartum period, with particular emphasis in maintaining or restoring the motherinfant relationship. PMID:20848086

  19. Changes in intestinal glucocorticoid sensitivity in early life shape the risk of epithelial barrier defect in maternal-deprived rats.

    PubMed

    Moussaoui, Nabila; Braniste, Viorica; Ait-Belgnaoui, Afifa; Gabanou, Mlissa; Sekkal, Soraya; Olier, Maiwenn; Thodorou, Vassilia; Martin, Pascal G P; Houdeau, Eric

    2014-01-01

    Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. Rat gut is immature at birth, and high intestinal GC sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of maternal separation (MS)-associated GC release in preterm babies, and whether GC sensitivity may shape MS effects in immature gut. A 4 hours-MS applied once at postnatal day (PND)10 enhanced plasma corticosterone in male and female pups, increased by two times the total in vivo intestinal permeability (IP) to oral FITC-Dextran 4 kDa (FD4) immediately after the end of MS, and induced bacterial translocation (BT) to liver and spleen. Ussing chamber experiments demonstrated a 2-fold increase of permeability to FD4 in the colon immediately after the end of MS, but not in the ileum. Colonic permeability was not only increased for FD4 but also to intact horseradish peroxidase 44 kDa in MS pups. In vivo, the glucocorticoid receptor (GR) antagonist RU486 or ML7 blockade of myosin light chain kinase controlling epithelial cytoskeleton contraction prevented MS-induced IP increase to oral FD4 and BT. In addition, the GR agonist dexamethasone dose-dependently mimicked MS-increase of IP to oral FD4. In contrast, MS effects on IP to oral FD4 and BT were absent at PND20, a model for full-term infant, characterized by a marked drop of IP to FD4 in response to dexamethasone, and decreased GR expression in the colon only compared to PND10 pups. These results show that high intestinal GC responsiveness in a rat model of prematurity defines a vulnerable window for a post-delivery MS, evoking immediate disruption of epithelial integrity in the large intestine, and increasing susceptibility to macromolecule passage and bacteremia. PMID:24586321

  20. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    PubMed Central

    Borengasser, Sarah J.; Faske, Jennifer; Kang, Ping; Blackburn, Michael L.; Badger, Thomas M.

    2014-01-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life. PMID:25336449

  1. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.

    PubMed

    Borengasser, Sarah J; Faske, Jennifer; Kang, Ping; Blackburn, Michael L; Badger, Thomas M; Shankar, Kartik

    2014-12-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (?16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)?, PGC1?, and estrogen-related receptor (ERR)?], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life. PMID:25336449

  2. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    PubMed Central

    Lee, Jong-Ho; Kim, Jin Young

    2014-01-01

    Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25031890

  3. Maternal dietary fat affects milk fatty acid profile and impacts on weight gain and thermogenic capacity of suckling rats.

    PubMed

    Priego, Teresa; Sánchez, Juana; García, Ana Paula; Palou, Andreu; Picó, Catalina

    2013-05-01

    We aimed to assess the effects of maternal supplementation with the main fat sources used in the human Western diet (olive oil, butter, margarine) on milk FA composition and on plasma FA profile of offspring, and to determine whether it may influence body-weight-gain (BWG) and adiposity of offspring during the suckling period. Wistar rats were supplemented with the different fat sources from day 14 of gestation and throughout lactation. Olive oil-supplemented dams showed the highest proportion of oleic-acid in milk, with no changes in plasma. Their offspring also showed the highest proportion of this FA in plasma, lower BWG during the suckling period, and higher levels of UCP1 in brown adipose tissue (BAT) at weaning. Margarine-supplemented dams showed the highest percentage of PUFA in milk, and a similar tendency was found in plasma of their offspring. Butter-supplemented dams displayed higher proportion of saturated FA (SFA) in milk compared to other fat-supplemented dams, but lower than controls. Control offspring also showed higher proportion of SFA in plasma and greater BWG during the suckling period than fat-supplemented groups. Significant correlations were found between the relative content of some milk FA and BWG of offspring, in particular, oleic-acid levels correlated negatively with BWG and positively with UCP1 levels. These results show that maternal dietary source of fat affects milk FA composition and circulating FA profile, as could be expected, but also BWG and thermogenic capacity of offspring during the suckling period. An effect of oleic-acid stimulating BAT thermogenic capacity of suckling pups is proposed. PMID:23417844

  4. Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders.

    PubMed

    Lino, Caroline A; da Silva, Ivson Bezerra; Shibata, Caroline E R; Monteiro, Priscilla de S; Barreto-Chaves, Maria Luiza M

    2015-11-15

    Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin-Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP,+dP/dT and -dP/dT at 25min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension. PMID:26277399

  5. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    PubMed

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring. PMID:26383539

  6. LPS Exposure Increases Maternal Corticosterone Levels, Causes Placental Injury and Increases IL-1? Levels in Adult Rat Offspring: Relevance to Autism

    PubMed Central

    Kirsten, Thiago B.; Lippi, Luciana L.; Bevilacqua, Estela; Bernardi, Maria M.

    2013-01-01

    Maternal immune activation can induce neuropsychiatric disorders, such as autism and schizophrenia. Previous investigations by our group have shown that prenatal treatment of rats on gestation day 9.5 with lipopolysaccharide (LPS; 100 ?g/kg, intraperitoneally), which mimics infections by gram-negative bacteria, induced autism-like behavior in male rats, including impaired communication and socialization and induced repetitive/restricted behavior. However, the behavior of female rats was unchanged. Little is known about how LPS-induced changes in the pregnant dam subsequently affect the developing fetus and the fetal immune system. The present study evaluated the hypothalamic-pituitary-adrenal (HPA) axis activity, the placental tissue and the reproductive performance of pregnant Wistar rats exposed to LPS. In the adult offspring, we evaluated the HPA axis and pro-inflammatory cytokine levels with or without a LPS challenge. LPS exposure increased maternal serum corticosterone levels, injured placental tissue and led to higher post-implantation loss, resulting in fewer live fetuses. The HPA axis was not affected in adult offspring. However, prenatal LPS exposure increased IL-1? serum levels, revealing that prenatal LPS exposure modified the immune response to a LPS challenge in adulthood. Increased IL-1? levels have been reported in several autistic patients. Together with our previous studies, our model induced autistic-like behavioral and immune disturbances in childhood and adulthood, indicating that it is a robust rat model of autism. PMID:24312647

  7. LPS exposure increases maternal corticosterone levels, causes placental injury and increases IL-1? levels in adult rat offspring: relevance to autism.

    PubMed

    Kirsten, Thiago B; Lippi, Luciana L; Bevilacqua, Estela; Bernardi, Maria M

    2013-01-01

    Maternal immune activation can induce neuropsychiatric disorders, such as autism and schizophrenia. Previous investigations by our group have shown that prenatal treatment of rats on gestation day 9.5 with lipopolysaccharide (LPS; 100 ?g/kg, intraperitoneally), which mimics infections by gram-negative bacteria, induced autism-like behavior in male rats, including impaired communication and socialization and induced repetitive/restricted behavior. However, the behavior of female rats was unchanged. Little is known about how LPS-induced changes in the pregnant dam subsequently affect the developing fetus and the fetal immune system. The present study evaluated the hypothalamic-pituitary-adrenal (HPA) axis activity, the placental tissue and the reproductive performance of pregnant Wistar rats exposed to LPS. In the adult offspring, we evaluated the HPA axis and pro-inflammatory cytokine levels with or without a LPS challenge. LPS exposure increased maternal serum corticosterone levels, injured placental tissue and led to higher post-implantation loss, resulting in fewer live fetuses. The HPA axis was not affected in adult offspring. However, prenatal LPS exposure increased IL-1? serum levels, revealing that prenatal LPS exposure modified the immune response to a LPS challenge in adulthood. Increased IL-1? levels have been reported in several autistic patients. Together with our previous studies, our model induced autistic-like behavioral and immune disturbances in childhood and adulthood, indicating that it is a robust rat model of autism. PMID:24312647

  8. Assessment of the perinatal effects of maternal ingestion of Ipomoea carnea in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is believed that I. carnea toxicosis induces abnormal embryogenesis in livestock. Studies with rats treated with I. carnea aqueous fraction (AF) during gestation, revealed litters with decreased body weight, but the characteristic vacuolar lesions promoted by swainsonine, its main toxic principle...

  9. EFFECTS ON THE FETUS OF MATERNAL NITROFEN EXPOSURE IN THE PROTEIN-DEPRIVED RAT

    EPA Science Inventory

    The separate and combined effects of protein deprivation and nitrofen exposure were studied in the pregnant rat. Animals were fed diets containing 24, 8, 6 or 4% casein throughout gestation. Within each diet group, sub-groups were gavage-fed with 12.5 (lower dose) and 25 (higher ...

  10. ASSESSMENT OF MATERNAL TOXICITY, EMBRYOTOXICITY AND TERATOGENIC POTENTIAL OF SODIUM CHLORITE IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Groups of up to 13 pregnant rats were individually caged. Body weight, food and water consumption were recorded at days 1, 8, 15 and 22 of gestation and the dams were treated on days 8-15 with sodium chlorite, 0.1%, 0.5% or 2% in drinking water or by injection of 10, 20, or 50 mg...

  11. OFFSPRING MORTALITY AND MATERNAL LUNG PATHOLOGY IN FEMALE RATS FED HEXACHLOROBENZENE

    EPA Science Inventory

    Female Sprague-Dawley CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of trea...

  12. Maternal lead exposure produces long-term enhancement of dopaminergic reactivity in rat offspring.

    PubMed

    Szczerbak, Grazyna; Nowak, Przemys?aw; Kostrzewa, Richard M; Brus, Ryszard

    2007-10-01

    To determine the effect of prenatal lead exposure on brain monoaminergic systems, pregnant rats were given tap water containing 250 ppm lead acetate, for the duration of pregnancy, while tap water without lead (Pb(2+)) was substituted at birth. Control rats were derived from dams that consumed tap water during pregnancy, and had no exposure to lead afterwards. At 12 weeks after birth, Pb(2+) content of brain cortex was increased 3- to 4-fold (P < 0.05). At this time the endogenous striatal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were 19% lower in Pb(2+) exposed rats (P < 0.05), while there was no change in the striatal level of dopamine (DA), noradrenaline, 3,4-dihydroxyphenylglycol, serotonin (5-HT) and 5-hydroxyindoleacetic acid (HPLC/ED). Also there was no change in these monoamines and metabolites in the prefrontal cortex of Pb(2+) exposed rats. However, turnover of 5-HT in prefrontal cortex, as indicated by 5-hydroxytryptophan accumulation 30 min after acute treatment with the decarboxylase inhibitor NSD-1015 (100 mg/kg IP), was lower in the Pb(2+) exposed rats. In the striatum AMPH-induced (1 mg/kg IP) turnover of DA, evidenced as L-DOPA accumulation after NSD-1015, was increased to a lesser extent in the Pb(2+) exposed rats (P < 0.05). The nitric oxide synthase inhibitor 7-nitroindazole (10 mg/kg IP) attenuated the latter effect, indicating that neuronal NO mediates this AMPH effect, at least in part. Moreover, DA D(2) receptor sensitivity developed in Pb(2+) exposed rats, as evidenced by enhanced quinpirole-induced yawning activity and enhanced quinpirole-induced locomotor activity (each, P < 0.05). These findings indicate that ontogenetic exposure to lead can have consequences on monoaminergic neuronal function at an adult stage of life, generally promoting accentuated behavioral effects of direct and indirect monoaminergic agonists, and related to increased dopamine turnover in basal ganglia. PMID:17404837

  13. Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring

    PubMed Central

    Clayton, Zoe E.; Vickers, Mark H.; Bernal, Angelica; Yap, Cassandra; Sloboda, Deborah M.

    2015-01-01

    Aim Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation. Methods Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR. Results Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes. Conclusions Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired immune sensing. PMID:26562417

  14. Nutrient-Dependent Requirement for SOD1 in Lifespan Extension by Protein Restriction in Drosophila melanogaster

    PubMed Central

    Sun, Xiaoping; Komatsu, Toshimitsu; Lim, Jinhwan; Laslo, Mara; Yolitz, Jason; Wang, Cecilia; Poirier, Luc; Alberico, Thomas; Zou, Sige

    2012-01-01

    Summary Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target-of-rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP and low calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high, and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions. PMID:22672579

  15. Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet.

    PubMed

    Camargo, Rafael L; Batista, Thiago M; Ribeiro, Rosane A; Branco, Renato C S; Da Silva, Priscilla M R; Izumi, Clarice; Araujo, Thiago R; Greene, Lewis J; Boschero, Antonio C; Carneiro, Everardo M

    2015-11-01

    Malnutrition programs the neuroendocrine axis by disruption of food-intake control, leading to obesity. Taurine (Tau) is neuroprotective and improves anorexigenic actions in the hypothalamus. We evaluated the hypothalamic gene-expression profile and food-intake control in protein-restricted mice submitted to a high-fat diet (HFD) and Tau supplementation. Mice were fed on a control (14 % protein-C) or a protein-restricted diet (6 % protein-R) for 6 weeks. Thereafter, mice received, or not, HFD for 8 weeks (CH and RH) with or without 5 % Tau supplementation (CHT and RHT). Protein restriction led to higher food intake, but calories were matched to controls. Excessive calorie intake occurred in HFD mice and this was prevented by Tau supplementation only in the CH group. Additionally, RH and CH mice developed hypothalamic leptin resistance, which was prevented by Tau. Global alterations in the expressions of genes involved in hypothalamic metabolism, cellular defense, apoptosis and endoplasmic reticulum stress pathways were induced by dietary manipulations and Tau treatment. The orexigenic peptides NPY and AgRP were increased by protein restriction and lowered by the HFD. The anorexigenic peptide Pomc was increased by HFD, and this was prevented by Tau only in CH mice. Thus, food intake was disrupted by dietary protein restriction and obesity. HFD-induced alterations were not enhanced by previous protein deficiency, but the some beneficial effects of Tau supplementation upon food intake were blunted by protein restriction. Tau effects upon feeding behavior control are complex and involve interactions with a vast gene network, preventing hypothalamic leptin resistance. PMID:26133737

  16. Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat.

    PubMed

    Bagot, Rosemary C; Zhang, Tie-Yuan; Wen, Xianglan; Nguyen, Thi Thu Thao; Nguyen, Huy-Binh; Diorio, Josie; Wong, Tak Pan; Meaney, Michael J

    2012-10-16

    Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring. Preliminary genome-wide analyses of gene transcription and DNA methylation of the molecular basis for such maternal effects suggested differences in the epigenetic state and transcriptional activity of the Grm1 gene in the rat as a function of maternal care. Grm1 encodes the type I metabotropic glutamate receptor (mGluR1), and we found increased mGluR1 mRNA and protein in hippocampus from the adult offspring of mothers showing an increased frequency of pup licking/grooming (i.e., high-LG mothers) that was associated with a decrease in the methylation of Grm1. ChIP assays showed increased levels of histone 3 lysine 9 acetylation and histone 3 lysine 4 trimethylation of Grm1 in hippocampus from the adult offspring of high-LG compared with low-LG mothers. These histone posttranslational modifications were highly correlated, and both associate inversely with DNA methylation and positively with transcription. Studies of mGluR1 function showed increased hippocampal mGluR1-induced long-term depression in the adult offspring of high-LG compared with low-LG mothers, as well as increased paired-pulse depression (PPD). PPD is an inhibitory feedback mechanism that prevents excessive glutamate release during high-frequency stimulation. The maternal effects on both long-term depression and PPD were eliminated by treatment with an mGluR1-selective antagonist. These findings suggest that variations in maternal care can influence hippocampal function and cognitive performance through the epigenetic regulation of genes implicated in glutamatergic synaptic signaling. PMID:23045678

  17. Maternal immune activation by polyriboinosinic-polyribocytidilic acid injection produces synaptic dysfunction but not neuronal loss in the hippocampus of juvenile rat offspring.

    PubMed

    Oh-Nishi, Arata; Obayashi, Shigeru; Sugihara, Izumi; Minamimoto, Takafumi; Suhara, Tetsuya

    2010-12-01

    It has been suggested that maternal immune activation increases the risk of psychiatric disorders such as schizophrenia in offspring. There are many reports about hippocampal structural pathology in schizophrenia. Antipsychotic drug administration in adolescence prevented postpubertal hippocampal structural pathology in the maternal immune activation animal model. These findings suggest the possibility that maternal immune activation induces hippocampal dysfunction in juvenile offspring. To test this hypothesis, we investigated hippocampal function in juvenile offspring of maternal immune activation model rat. A synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C; 4 mg/kg/day, I.P.) was injected to pregnant rats on gestation days 15 and 17, in order to cause immune activation by stimulating Toll-like receptor 3. Hippocampal synaptic function and morphology in their juvenile offspring (postnatal days 28-31) were compared to those in vehicle-injected control offspring. Field responses were recorded in the hippocampal CA1 region by stimulating commissural/Schaffer collaterals. Pre-synaptic fiber volley amplitudes (mV) and field excitatory post-synaptic potential slopes (mV/ms) were significantly lower in treated offspring. In addition, short-term synaptic plasticity, namely, the paired-pulse facilitation ratio, was significantly higher and long-term synaptic plasticity (long-term potentiation) was significantly impaired in treated offspring. Furthermore, major pre-synaptic protein (synaptophysin) expressions were decreased, but not major post-synaptic proteins (GluR1, GluR2/3, and NR1), in hippocampal CA1 of treated offspring, whereas neuronal loss was not detected in the hippocampal CA1-CA3 regions. These results indicate that maternal immune activation leads to synaptic dysfunction without neuronal loss in the hippocampus of juvenile offspring, and this may be one of the early stages of schizophrenia pathologies. PMID:20863817

  18. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. PMID:26632603

  19. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  20. Nephron number and blood pressure in rat offspring with maternal high-protein diet.

    PubMed

    Zimanyi, Monika A; Bertram, John F; Black, M Jane

    2002-12-01

    This study investigated the effects of a high-protein diet during pregnancy on nephron endowment and subsequent levels of blood pressure in the offspring. Female WKY rats were fed either a normal (20%, NPD) or a high (54%, HPD) protein diet during pregnancy. Male offspring were paired at birth. At 4 weeks of age, 1 of the pair was randomly chosen for perfusion fixation, and total glomerular number, and thereby nephron number, was estimated using an unbiased stereological technique. The other rat of the pair was allowed to grow to 30 weeks of age, during which time tail cuff systolic blood pressure was monitored twice weekly. There was no effect of the HPD on birth weight (NPD 4.23+/-0.53 g, HPD 4.26+/-0.45 g, mean+/-SD), kidney weight (NPD 0.372+/-0.049 g, HPD 0.337+/-0.090 g), or total nephron number (NPD 27,191+/-3,512, HPD 26,738+/-4,735). Systolic blood pressure at 30 weeks was 170+/-14 mmHg in NPD and 169+/-14 in HPD offspring. These findings show that a HPD during pregnancy did not lead to an increase in birth weight, kidney weight, or nephron endowment, nor did the HPD affect adult blood pressure. PMID:12478348

  1. Role of metallothionein induction and altered zinc status in maternally mediated developmental toxicity: Comparison of the effects of urethane and styrene in rats

    SciTech Connect

    Daston, G.P.; Overmann, G.J.; Taubeneck, M.W.; Lehman-McKeeman, L.D.; Rogers, J.M.

    1991-01-01

    The authors hypothesize that maternal metallothionein (MT) induction by toxic dosages of chemicals may contribute to or cause developmental toxicity by a chain of events leading to a transient but developmentally adverse decrease in Zn availability to the embryo. The hypothesis was tested by evaluating hepatic MT induction, maternal and embryonic Zn status, and developmental toxicity after exposure to urethane, a developmental toxicant, or styrene, which is not a developmental toxicant. Pregnant Sprague-Dawley rats were given 0 or 1 g/kg urethane ip, or 0 or 300 mg/kg styrene in corn oil po, on Gestation Day 11 (sperm positive = Gestation Day 0). These were maternally toxic dosages. As both treatments decreased food consumption, separate pair-fed control groups were also evaluated for effects on MT and Zn status and development. In addition, Gestation Day 11 rat embryos were exposed to urethane in vitro in order to determine whether urethane has the potential to be directly embryotoxic. Urethane treatment induced hepatic MT 14-fold over control; styrene treatment induced MT 2.5-fold. The MT induction by styrene could be attributed to decreased food intake, as a similar level of induction was observed in a pair-fed untreated control group. However, the level of MT induction by urethane was much greater than that produced by decreased food intake alone. (Copyright (c) 1991 Academic Press, Inc.)

  2. Maternal fructose consumption alters messenger RNA expression of hippocampal StAR, PBR, P450(11?), 11?-HSD, and 17?-HSD in rat offspring.

    PubMed

    Ohashi, Koji; Ando, Yoshitaka; Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Nagura, Ayuri; Taromaru, Nao; Ishikawa, Hiroaki; Suzuki, Koji; Teradaira, Ryouji

    2015-03-01

    Hippocampal functions such as neuronal protection and synapse formation are positively modulated by neurosteroids, which are synthesized de novo within the brain. However, the mechanisms regulating neurosteroidogenesis remain unclear. Fructose, which is used as a sweetener, affects steroid hormone synthesis in peripheral endocrine organs. This monosaccharide can penetrate the blood-brain barrier and impair hippocampal function. Also, fructose is secreted into milk and is thus delivered to the fetus. Based on these observations, we hypothesized that the hippocampal neurosteroidogenesis in the offspring may be affected by maternal fructose consumption. Female rats were fed with normal water or 20% fructose solution during gestation and lactation. Maternal calorie intake did not change significantly, and no significant change in body weight was observed. The levels of messenger RNAs (mRNAs) for steroidogenic enzymes and proteins in the hippocampus of the offspring were analyzed by real-time reverse transcriptase polymerase chain reaction. Maternal fructose consumption during gestation and lactation increased mRNA levels of P450(11?)-2, 11?-HSD-2, and 17?-HSD-1 in the offspring hippocampus, and reduced levels of mRNAs for StAR, PBR, and 17?-HSD-3. Maternal fructose consumption might influence hippocampal neurosteroidogenesis in offspring. PMID:25554348

  3. Effects of maternally exposed colouring food additives on cognitive performance in rats.

    PubMed

    Doguc, Duygu Kumbul; Ceyhan, Betul Mermi; Ozturk, Mustafa; Gultekin, Fatih

    2013-08-01

    Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. Effects on spatial learning and memory were evaluated by Morris water maze, behavioural effects were evaluated by open-field test and forced swim test. Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity. PMID:22323474

  4. Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups.

    PubMed

    Bazrgar, Maryam; Goudarzi, Iran; Lashkarbolouki, Taghi; Elahdadi Salmani, Mahmoud

    2015-11-01

    During the particular period of cerebellum development, exposure to lead (Pb) decreases cerebellum growth and can result in selective loss of neurons. The detection and prevention of Pb toxicity is a major international public health priorities. This research study was conducted to evaluate the effects of melatonin, an effective antioxidant and free radical scavenger, on Pb induced neurotoxicity and oxidative stress in the cerebellum. Pb exposure was initiated on gestation day 5 with the addition of daily doses of 0.2% lead acetate to distilled drinking water and continues until weaning. Melatonin (10mg/kg) was given once daily at the same time. 21 days after birth, several antioxidant enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed. Thiobarbituric acid reactive substance (TBARS) levels were measured as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed on postnatal days (PDs) 31-33 and a histological study was performed after completion of behavioral measurements on PD 33. The results of the present work demonstrated that Pb could induce lipid peroxidation, increase TBARS levels and decrease GPx and SOD activities in the rat cerebellum. We also observed that Pb impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated the motoric impairment and lipid peroxidation process and restored the levels of antioxidants. Histological analysis indicated that Pb could decrease Purkinje cell count and melatonin prevented this toxic effect. These results suggest that treatment with melatonin can improve motor deficits and oxidative stress by protecting the cerebellum against Pb toxicity. PMID:26197271

  5. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation.

    PubMed

    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  6. Maternal deprivation disrupts mitochondrial energy homeostasis in the brain of rats subjected to ketamine-induced schizophrenia.

    PubMed

    Zugno, Alexandra Ioppi; Pacheco, Felipe Damázio; Budni, Josiane; de Oliveira, Mariana Bittencourt; Canever, Lara; Heylmann, Alexandra Stephanie; Wessler, Patrícia Gomes; da Rosa Silveira, Flávia; Mastella, Gustavo Antunes; Gonçalves, Cinara Ludwig; Freitas, Karoline V; de Castro, Adalberto Alves; Streck, Emilio L; Quevedo, João

    2015-08-01

    Maternal deprivation (MD) appears to be one of the environmental factors involved in the pathophysiology of schizophrenia. A widely used animal model of the schizophrenia involves the administration of ketamine, a dissociative anesthetic, NMDA receptors noncompetitive antagonist, that induce symptoms such as schizophrenia. To clarify the molecular mechanism of schizophrenia induced by MD, we investigated alterations in energetic metabolism, oxidative stress and neurotrophic factor levels in the brain of rats following MD and/or a single administration of ketamine during adulthood. Male Wistar rats were subjected to MD for 10 days. Additionally, these animals received acute ketamine (5, 15 or 25 mg/kg by intraperitoneal route, i.p.) during adulthood, and 30 min later, they were killed and the prefrontal cortex (PFC), the hippocampus and the striatum were removed for molecular analyses. Ketamine 25 mg/kg and/or MD and Ketamine 15 and 5 mg/kg with MD decreased the creatine kinase (CK) activity in the hippocampus. The enzyme activity of succinate dehydrogenase (SDH) in the Krebs cycle had increased in the striatum following the administration of ketamine 25 mg/kg, MD per se or MD plus ketamine 5 and 15 mg/kg. MD per se or MD combined with ketamine in different doses increased the activity of mitochondrial complexes. The PFC of animals subjected to MD and administered with ketamine 5 mg/kg exhibited increased protein carbonyl content. In the hippocampus, ketamine 15 mg/kg, ketamine 25 mg/kg and MD each increased the carbonyl content. In the striatum, the TBARS levels were increased by the administration of ketamine 25 mg/kg. Finally, in the hippocampus, MD alone or in combination with ketamine reduced the Nerve Growth Factor (NGF) levels; however, the Brain-derived Neurotrophic Factor (BDNF) levels were unaltered. In the present study, we suggest that MD increased the risk of psychotic symptoms in adulthood, altering different parameters of energy and oxidative stress. Our results suggest that adverse experiences occurring early in life may sensitize specific neurocircuits to subsequent stressors, inducing vulnerability, and may help us understand the pathophysiological mechanisms involved in this disorder. PMID:25920483

  7. Maternal taurine supplementation in the late pregnant rat stimulates postnatal growth and induces obesity and insulin resistance in adult offspring

    PubMed Central

    Hultman, Karin; Alexanderson, Camilla; Mannerås, Louise; Sandberg, Mats; Holmäng, Agneta; Jansson, Thomas

    2007-01-01

    An adequate supply of taurine during fetal life is important for normal beta-cell development and insulin action. An altered availability of taurine may programme glucose metabolism in utero and result in type 2 diabetes in adult age. We examined whether maternal taurine supplementation in late pregnant rats affects postnatal growth, adult body composition, insulin sensitivity and endogenous insulin secretion in intrauterine growth restricted (IUGR) and normal offspring. Uterine artery ligation or sham operations were performed on gestational day (GD) 19. Taurine supplementation was given to half of the dams from GD 18 until term, resulting in four groups of offspring: sham (n = 22), sham/taurine (n = 22), IUGR (n = 22) and IUGR/taurine (n = 24). The offspring were studied at 12 weeks of age. In offspring with normal birth weight, fetal taurine supplementation markedly stimulated postnatal growth. In sham/taurine females, fat depots, plasma free fatty acid and leptin concentrations were increased, and insulin sensitivity was reduced. Insulin sensitivity was unaltered in IUGR and IUGR/taurine offspring. However, whereas IUGR offspring showed little catch-up growth, 50% of IUGR/taurine animals displayed complete catch-up at 12 weeks of age, and these animals had increased fat depots and reduced insulin sensitivity. In conclusion, taurine supplementation in late gestation resulted in accelerated postnatal growth, which was associated with adult obesity and insulin resistance in both IUGR and normal offspring. This effect was particularly evident in females. These data suggest that fetal taurine availability is an important determinant for postnatal growth, insulin sensitivity and fat accumulation. PMID:17204495

  8. Growth, development and activity in rat offspring following maternal drug exposure.

    PubMed

    Martin, J C; Martin, D C; Radow, B; Sigman, G

    1976-05-01

    Seventy-nine Sprague-Dawley derived primimparous rats were injected subcutaneously throughout pregnancy and the nursing period with either (1) 30 mg/kg of pure nicotine, (2) 5.0 mg/kg methamphetamine HCL, (3) saline vehicle, or, (4) non-injected. Vital and developmental measures were taken on the offspring throughout the nursing period and for one additional week. Metamphetamine-injected females had a shorter, and nicotine-injected females a longer gestational period, and both gained less weight over the 21-day period than the control groups. The pups of methamphetamine and nicotine dams were significantly underweight at birth and the 28 day postnatal period and exhibited developmental delay. Male offspring were divided into behavioral, aging, and autopsy on Day 28. Male offspring of methamphetamine-injected dams remained significantly lighter in weight for the first 15 months of life (aging groups). Their counterparts in the behavioral groups and the offspring of non-injected dams exhibited significantly greater activity for eight of the first twelve monthly assessments which began at 90 days of age. Additional vital, performance, and sensory measures will continue throughout the lifespan of the animals. PMID:1017447

  9. Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

    PubMed

    Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

    2016-01-01

    Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. PMID:26746106

  10. Programmed regulation of rat offspring adipogenic transcription factor (PPAR?) by maternal nutrition.

    PubMed

    Desai, M; Jellyman, J K; Han, G; Lane, R H; Ross, M G

    2015-12-01

    We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPAR?) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPAR? with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPAR? with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPAR? expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPAR? co-regulators are necessary to establish their role in PPAR?-mediated programmed obesity. PMID:26286138

  11. Effect of Caffeine Chronically Consumed During Pregnancy on Adenosine A1 and A2A Receptors Signaling in Both Maternal and Fetal Heart from Wistar Rats

    PubMed Central

    Iglesias, Inmaculada; Albasanz, Jose Luis

    2014-01-01

    Background: Caffeine is the most widely consumed psychoactive substance in the world, even during pregnancy. Its stimulatory effects are mainly due to antagonism of adenosine actions by blocking adenosine A1 and A2A receptors. Previous studies have shown that caffeine can cross the placenta and therefore modulate these receptors not only in the fetal brain but also in the heart. Methods: In the present work, the effect of caffeine chronically consumed during pregnancy on A1 and A2A receptors in Wistar rat heart, from both mothers and their fetuses, were studied using radioligand binding, Western-blotting, and adenylyl cyclase activity assays, as well as reverse transcription polymerase chain reaction. Results: Caffeine did not significantly alter A1R neither at protein nor at gene expression level in both the maternal and fetal heart. On the contrary, A2AR significantly decreased in the maternal heart, although mRNA was not affected. Gi and Gs proteins were also preserved. Finally, A1R-mediated inhibition of adenylyl cyclase activity did not change in the maternal heart, but A2AR mediated stimulation of this enzymatic activity significantly decreased according to the detected loss of this receptor. Conclusions: Opposite to the downregulation and desensitization of the A1R/AC pathway previously reported in the brain, these results show that this pathway is not affected in rat heart after caffeine exposure during pregnancy. In addition, A2AR is downregulated and desensitized in the maternal heart, suggesting a differential modulation of these receptor-mediated pathways by caffeine. PMID:25538864

  12. Maternal Exposure to Low Levels of Corticosterone during Lactation Protects against Experimental Inflammatory Colitis-Induced Damage in Adult Rat Offspring

    PubMed Central

    Petrella, Carla; Giuli, Chiara; Agostini, Simona; Bacquie, Valrie; Zinni, Manuela; Theodorou, Vassilia; Broccardo, Maria; Casolini, Paola; Improta, Giovanna

    2014-01-01

    Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a positive experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted to colonic inflammatory stress, constitute a useful experimental model to investigate the etiopathogenetic mechanisms and therapeutic treatments of some gastrointestinal diseases. PMID:25405993

  13. Maternal exposure to low levels of corticosterone during lactation protects against experimental inflammatory colitis-induced damage in adult rat offspring.

    PubMed

    Petrella, Carla; Giuli, Chiara; Agostini, Simona; Bacquie, Valérie; Zinni, Manuela; Theodorou, Vassilia; Broccardo, Maria; Casolini, Paola; Improta, Giovanna

    2014-01-01

    Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a "positive" experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted to colonic inflammatory stress, constitute a useful experimental model to investigate the etiopathogenetic mechanisms and therapeutic treatments of some gastrointestinal diseases. PMID:25405993

  14. A maternal high fat diet has long-lasting effects on skeletal muscle lipid and PLIN protein content in rat offspring at young adulthood.

    PubMed

    MacPherson, Rebecca E K; Castelli, Laura M; Miotto, Paula M; Frendo-Cumbo, Scott; Milburn, Amanda; Roy, Brian D; LeBlanc, Paul J; Ward, Wendy E; Peters, Sandra J

    2015-02-01

    A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI-58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19 d) and young adulthood (3 mo). Female rats (28 d old, n = 9/group) were fed control (CON, AIN93G, 7% soybean oil) or HFD (AIN93G, 20% lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19 d) and 3 mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3 mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3 mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3 mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI-58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood. PMID:25552350

  15. Dynamic changes in lipids and proteins of maternal, fetal, and pup blood and milk during perinatal development in CD and Wistar rats.

    PubMed

    McMullin, Tami S; Lowe, Ezra R; Bartels, Michael J; Marty, Mary Sue

    2008-10-01

    An understanding of the physiological factors that regulate perinatal dosimetry is essential to improve the ability of physiologically based (PB) pharmacokinetic (PK) models to predict chemical risks to children. However, the impact of changing maternal/offspring physiology on PK during gestation and lactation remains poorly understood. This research determined lipid and protein changes in blood, milk and amniotic fluid of CD and Wistar dams, fetuses and neonates to improve the precision of perinatal PBPK modeling. Samples were collected from time-mated CD dams, fetuses, and pups on gestation day (GD) 18 and 20 (sperm positive = GD 0) or lactation day 0 (day of birth), 1, 3, 5, 10, 15, and 20 (n > or = 5 per time point). Fewer time points were sampled in Wistar rats, which showed similar patterns to CDs. Relative to nonpregnant dams, maternal serum protein levels (albumin, total protein and globulin) each decreased by approximately 20% during late gestation, whereas maternal serum lipids (triglycerides, low density lipoproteins, and phospholipids) increased up to fourfold. These physiological changes can impact maternal PK of both protein-bound and lipophilic chemicals. During lactation, triglycerides in milk were greater than 100-fold higher than maternal serum, favoring the disposition of lipophilic chemicals into milk and potentially increasing neonatal rodent exposure during critical stages of postnatal development. Serum protein levels in pups were two- to threefold lower than adults at birth, which may increase the bioavailability of protein-bound compounds. These data will aid in the interpretation of perinatal toxicity studies and improve the accuracy of predictive perinatal PBPK models. PMID:18593729

  16. Effects of maternal lead exposure on central nervous system maturation in postnatal rats

    SciTech Connect

    Coleman, J.C.

    1984-01-01

    Pups from female rats exposed to 40-to-80 mg of lead per liter in their drinking water (low-lead group) and 160-to-320 mg of lead per liter water (high-lead group) were examined at 1 to 18 days of age. Maximal electroshock seizure (MES) patterns were determined and, upon recovery, whole blood, plasma, cerebrospinal fluid (CSF) and cerebral cortex samples were collected. Approximately one-half of the pups was used to determine the cerebral cortical extracellular water space (ECS). The other half was used to determine whole blood lead concentrations, plasma electrolytes (Na/sup +/, K/sup +/ and Cl/sup -/), CSF electrolytes, and cerebral cortical lead content, electrolytes, total water spaces, protein content, DNA content, carbonic anhydrase (CA) activity, and sodium- potassium-activated adenosinetriphosphatase (Na/sup +//K/sup +/-ATPase) activity. Neither the low- nor the high-lead groups had significant changes in body weight, body length, hematocrit or cerebral wet weight at any age studied. Whole blood and cerebral cortical lead contents were increased, dose-dependently, at each day of age. Hyperexcitability as measured by MES was observed in lead-exposed pups at 6, 9 and 12 days of age. These observations demonstrate that prenatal and postnatal exposure to lead causes increased susceptibility to MES and alterations in normal developmental patterns of the cerebral cortex. Such alterations appear to result from the greater vulnerability of the glial population to the adverse effects of lead than are neutrons. Thus, effects on the glia can account for the electrolyte imbalances, cellular edema and hyperexcitability resulting from exposure to lead.

  17. Maternal ethanol ingestion: effect on maternal and neonatal glucose balance

    SciTech Connect

    Witek-Janusek, L.

    1986-08-01

    Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rate. Female rats were placed on 1) the Lieber-DeCarli liquid ethanol diet, 2) an isocaloric liquid pair-diet, or 3) an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat.

  18. In utero glucocorticoid (GLC) exposure and maternal undernutrition reduce fetal skeletal muscle mass by different mechanisms in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Both maternal undernutrition and exposure of the fetus to above normal levels of GLC impair skeletal muscle growth. The degree to which the effects of maternal undernutrition on fetal skeletal muscle growth are a direct result of nutrient deficit or secondary to the presence of above normal GLC leve...

  19. Maternal low protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1 mediated thermogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  20. Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low-protein diet in the rat.

    PubMed

    Sherman, R C; Langley-Evans, S C

    1998-04-01

    1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of 'programmed' hypertension was used to investigate the role of the renin-angiotensin system in the initiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24-25 mmHg higher than those of rats exposed to a control diet in utero. 4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopril-treated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero. 6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals. PMID:9640343

  1. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.

    PubMed Central

    Calvo, R; Obregn, M J; Ruiz de Oa, C; Escobar del Rey, F; Morreale de Escobar, G

    1990-01-01

    To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be clinically euthyroid if their T3 levels are normal. Images PMID:2394838

  2. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    PubMed Central

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  3. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

    PubMed

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring. PMID:26771675

  4. Dietary protein and lifespan across the metamorphic boundary: protein-restricted larvae develop into short-lived adults

    PubMed Central

    Runagall-McNaull, A.; Bonduriansky, R.; Crean, A. J.

    2015-01-01

    Restriction of nutrients in the adult diet extends lifespan across a diverse range of species, but less is known about the long-term effects of developmental dietary restriction. In particular, it is not known whether adult lifespan is influenced by developmental caloric restriction or macronutrient balance. We used the nutritional geometry approach to independently manipulate protein and carbohydrate contents of the larval diet in the neriid fly, Telostylinus angusticollis, and measured adult lifespan. We found that adult male and female lifespan was shortest when larvae were fed a protein restricted diet. Thus, protein restriction in the larval diet has the opposite effect of protein restriction in the adult diet (which prolongs life in this species and across a wide range of taxa). Adult lifespan was unaffected by larval dietary carbohydrate. These patterns persisted after controlling for larval diet effects on adult body size. We propose that larval and adult protein sources are used for distinct metabolic tasks: during development, dietary protein is used to build a durable soma that enhances adult lifespan, although excessive protein consumption partially reverses this effect. PMID:26119686

  5. Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1.

    PubMed

    Sun, Xiu-Min; Tu, Wen-Qiang; Shi, Yan-Wei; Xue, Li; Zhao, Hu

    2014-07-01

    Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including ?2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS. PMID:24667363

  6. Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring.

    PubMed

    Chandna, A R; Kuhlmann, N; Bryce, C A; Greba, Q; Campanucci, V A; Howland, J G

    2015-09-10

    Maternal diabetes during pregnancy may increase the risk of neurodevelopmental disorders in the offspring by increasing inflammation. A major source of inflammatory signaling observed in diabetes is activation of the receptor for advanced glycation end-products (RAGE), and increased RAGE expression has been reported in psychiatric disorders. Thus, we sought to examine whether maternal diabetes creates a proinflammatory state, triggered largely by RAGE signaling, that alters normal brain development and behavior of the offspring. We tested this hypothesis in rats using the streptozotocin (STZ; 50mg/kg; i.p.) model of diabetes induced during mid-pregnancy. Following STZ treatment, we observed a significant increase in RAGE protein expression in the forebrain of the offspring (postnatal day 1). Data obtained from whole-cell patch clamping of hippocampal neurons in cultures from the offspring of STZ-treated dams revealed a striking increase in excitability. When tested in a battery of behavioral tasks in early adulthood, the offspring of STZ-treated dams had significantly lower prepulse inhibition, reduced anxiety-like behavior, and altered object-place preference when compared to control offspring. In an operant-based strategy set-shifting task, STZ offspring did not differ from controls on an initial visual discrimination or reversal learning but took significantly longer to shift to a new strategy (i.e., set-shift). Insulin replacement with an implantable pellet in the dams reversed the effects of maternal diabetes on RAGE expression, hippocampal excitability, prepulse inhibition and object-place memory, but not anxiety-like behavior or set-shifting. Taken together, these results suggest that chronic maternal hyperglycemia alters normal hippocampal development and behavior of the offspring, effects that may be mediated by increased RAGE signaling in the fetal brain. PMID:26151680

  7. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation

    PubMed Central

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-01-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut. PMID:26493953

  8. Combined c-fos and 14C-2-deoxyglucose method to differentiate site-specific excitation from disinhibition: analysis of maternal behavior in the rat.

    PubMed

    Komisaruk, B R; Rosenblatt, J S; Barona, M L; Chinapen, S; Nissanov, J; O'Bannon, R T; Johnson, B M; Del Cerro, M C

    2000-03-24

    On the basis of evidence that 14C-2-deoxyglucose (2-DG) autoradiography indicates activity at axonal terminals, whereas c-fos immunocytochemistry indicates activity of neuronal cell bodies, we combined these techniques in adjacent histological brain sections to assess excitatory and disinhibitory synaptic relations in selected sites in female rats in which maternal behavior was elicited by natural parturition, sensitization (7- to 10-day cohabitation with foster pups), or hysterectomy. All individuals in these three groups expressed maternal behavior immediately before 2-DG injection. Controls were non-maternal virgins. Parturient and Hysterectomized groups: elevation (compared with controls) in both 2-DG and c-fos activity in medial preoptic area (MPOA) indicated an increase in its input and output activity, i.e., an excitatory interaction; the MPOA was previously shown to be critical for maternal behavior. Sensitized group: a decrease in 2-DG activity of vomeronasal nuclei (bed nucleus of the accessory olfactory tract, BAOT, and medial amygdala, ME, replicating our previous study) and an elevation in c-fos activity, jointly indicate disinhibition of these nuclei, that were previously shown to modulate pup-chemostimulation-induced sensitization. All other sites showed evidence of excitatory input-output relationships (i.e., joint increase in both 2-DG and c-fos activity), e.g., bed nucleus of the stria terminalis (BNST), lateral habenula (LHAB), central gray (CG), thalamus (THAL), septum (SEPT), and ventral tegmental area (VTA). The present study demonstrates the feasibility of measuring 2-DG and c-fos activity jointly in adjacent sections of the same brain, thereby providing evidence to distinguish between localized excitation and disinhibition. PMID:10719073

  9. Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

    PubMed Central

    Knaepen, Liesbeth; Rayen, Ine; Charlier, Thierry D.; Fillet, Marianne; Houbart, Virginie; van Kleef, Maarten; Steinbusch, Harry W.; Patijn, Jacob; Tibboel, Dick; Joosten, Elbert A.; Pawluski, Jodi L.

    2013-01-01

    Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system. PMID:23437400

  10. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-10-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1? and TNF? concentrations. Gut Tas1R1, IL-1?, TNF?, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut. PMID:26493953

  11. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

    PubMed

    Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

    2015-02-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

  12. Oral Leptin Treatment in Suckling Rats Ameliorates Detrimental Effects in Hypothalamic Structure and Function Caused by Maternal Caloric Restriction during Gestation

    PubMed Central

    Konieczna, Jadwiga; Garca, Ana Paula; Snchez, Juana; Palou, Mariona; Palou, Andreu; Pic, Catalina

    2013-01-01

    A poor prenatal environment brings about perturbations in leptin surge and hypothalamic circuitry that program impaired ability to regulate energy homeostasis in adulthood. Here, using a rat model of moderate maternal caloric restriction during gestation, we aimed to investigate whether leptin supplementation with physiological doses throughout lactation is able to ameliorate the adverse developmental malprogramming effects exerted in offspring hypothalamus structure and function. Three groups of male and female rats were studied: the offspring of ad libitum fed dams (controls), the offspring of 20% calorie restricted dams during the first part of pregnancy (CR), and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Animals were sacrificed on postnatal day 25. Morphometric and immunohistochemical studies on arcuate (ARC) and paraventicular (PVN) nucleus were performed and hypothalamic expression levels of selected genes were determined. In CR males, leptin treatment restored, at least in part, the number of immunoreactive neuropeptide Y (NPY+) cells in ARC, the total number of cells in PVN, hypothalamic NPY, cocaine- and amphetamine-regulated transcript (CART) and suppressor of cytokine signalling-3 (SOCS-3) mRNA levels, and plasma leptin levels, which were decreased in CR animals. CR-Leptin males showed higher hypothalamic long-form leptin receptor (ObRb) mRNA levels, compared to control and CR animals. In CR females, leptin treatment reverted the increased number of cells in ARC and cell density in ARC and PVN, and reduced hypothalamic SOCS-3 mRNA expression to levels similar to controls. Leptin treatment also reverted the increased relative area of NPY+ fibers in the PVN occurring in CR animals. In conclusion, leptin supplementation throughout lactation is able to revert, at least partly, most of the developmental effects on hypothalamic structure and function caused by moderate maternal caloric restriction during gestation, and hence making this metabolic malprogramming reversible to some extent. PMID:24312379

  13. A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development.

    PubMed

    Boudalia, Sofiane; Berges, Raymond; Chabanet, Claire; Folia, Mireille; Decocq, Laurence; Pasquis, Bruno; Abdennebi-Najar, Latifa; Canivenc-Lavier, Marie-Chantal

    2014-01-01

    Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats. BPA was orally administered at a daily dose of 5 ?g/kg body weight to F0 pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to F1 offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as "non-maternal" behaviors in F0 and F1 dams from parturition until LD 8. The flavor preferences of F1 and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21-34 and PND 86-99. BPA exposure: 1) decreased maternal behavior in F1 dams, 2) caused developmental defects in both F1 and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in F1, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change. Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure. PMID:24269606

  14. Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    PubMed Central

    2012-01-01

    Background Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH. Results CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. Conclusion The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS. PMID:23249427

  15. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay

    PubMed Central

    Barreau, Frederick; Cartier, Christel; Leveque, Mathilde; Ferrier, Laurent; Moriez, Raphael; Laroute, Valerie; Rosztoczy, Andras; Fioramonti, Jean; Bueno, Lionel

    2007-01-01

    Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2–14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), α-helical CRF(9-41) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R1 receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R1 receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R1 receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier. PMID:17234701

  16. Visceral hyperalgesia induced by neonatal maternal separation is associated with nerve growth factor-mediated central neuronal plasticity in rat spinal cord.

    PubMed

    Chung, E K Y; Zhang, X-J; Xu, H-X; Sung, J J Y; Bian, Z-X

    2007-11-01

    Neonatal maternal separation (NMS) has been shown to trigger alterations in neuroendocrine, neurochemical and sensory response to nociceptive stimuli along the brain-gut axis. These alterations may be the result of a cascade of events that are regulated by neurotrophic factors. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for the development and maintenance of sensory neurons and for the formation of central pain circuitry. The present study aimed to investigate whether NMS causes changes in neuronal plasticity and the relationship of these changes in plasticity with the expression of NGF and its high affinity tyrosine kinase receptor A (TrkA) in the lumbosacral spinal cord in adult rats. Male Wistar rat pups were either subjected to 180 min daily of NMS or not handled (NH) for 13 consecutive days. The expression of NGF and TrkA was examined in NH and NMS rats with or without colorectal distention (CRD) as determined by Western blot analysis and immunohistochemistry. The present results of Western blot analysis indicated NMS and CRD have a significant effect on NGF protein level in the lumbosacral spinal cord of rats. Assessments of optical densities revealed that NMS enhanced TrkA-ir fiber densities in laminae I-III and laminae V-VI of rats in both conditions with or without CRD. Double immunofluorescence revealed that TrkA co-expressed with calcitonin gene-related peptide (CGRP) in afferent fibers, while no significant difference in terms of the intensity of TrkA-ir in these fibers was found among groups. Quantitative analysis of TrkA-ir neurons indicated a significant interactive effect of NMS and CRD on the mean number of TrkA-ir neurons in laminae V-VI of rats, in which significant difference was found between NMS+CRD and NH+CRD. Double immunofluorescence of TrkA and Fos showed that CRD has a significant effect on TrkA expression in Fos-positive neurons in laminae V-VI and lamina X of rats, while no significant difference was found between NMS+CRD and NH+CRD. These results demonstrate that NMS induced alterations in NGF protein level and TrkA expression in adult rat spinal cord and indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia. PMID:17913374

  17. Maternal microchimerism

    PubMed Central

    Ye, Jody; Vives-Pi, Marta; Gillespie, Kathleen M

    2014-01-01

    Increased levels of non-inherited maternal HLA alleles have been detected in the periphery of children with type 1 diabetes and an increased frequency of maternal cells have been identified in type 1 diabetes pancreas. It is now clear that the phenotype of these cells is pancreatic,1 supporting the hypothesis that maternal cells in human pancreas are derived from multipotent maternal progenitors. Here we hypothesize how increased levels of maternal cells could play a role in islet autoimmunity. PMID:25093746

  18. Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure

    PubMed Central

    Bossi, Rossana; Vinggaard, Anne Marie; Taxvig, Camilla; Boberg, Julie; Bonefeld-Jrgensen, Eva Cecilie

    2013-01-01

    Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds. PMID:23736656

  19. Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.

    PubMed

    Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika

    2010-01-01

    The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis. PMID:20617189

  20. EFFECT OF VARYING MATERNAL FOLATE STATUS AND DIETARY FOLATE INTAKE ON RESPONSE TO DIVERSE DEVELOPMENTAL TOXICANTS IN THE RAT

    EPA Science Inventory

    Periconceptional and early pregnancy folate supplements are associated with reduced recurrence and occurrence of birth defects in humans. This study was undertaken to assess the influence of maternal folate status and dietary folate intake on outcome of exposures to diverse terat...

  1. Maternal Nutrient Restriction Alters Ca2+ Handling Properties and Contractile Function of Isolated Left Ventricle Bundles in Male But Not Female Juvenile Rats

    PubMed Central

    Murphy, Robyn M.; Morrison, Janna L.

    2015-01-01

    Intrauterine growth restriction (IUGR), defined as a birth weight below the 10th centile, may be caused by maternal undernutrition, with evidence that IUGR offspring have an increased risk of cardiovascular disease (CVD) in adulthood. Calcium ions (Ca2+) are an integral messenger for several steps associated with excitation-contraction coupling (ECC); the cascade of events from the initiation of an action potential at the surface membrane, to contraction of the cardiomyocyte. Any changes in Ca2+ storage and release from the sarcoplasmic reticulum (SR), or sensitivity of the contractile apparatus to Ca2+ may underlie the mechanism linking IUGR to an increased risk of CVD. This study aimed to explore the effects of maternal nutrient restriction on cardiac function, including Ca2+ handling by the SR and force development by the contractile apparatus. Juvenile Long Evans hooded rats born to Control (C) and nutrient restricted (NR) dams were anaesthetized for collection of the heart at 1012 weeks of age. Left ventricular bundles from male NR offspring displayed increased maximum Ca2+-activated force, and decreased protein content of troponin I (cTnI) compared to C males. Furthermore, male NR offspring showed a reduction in rate of rise of the caffeine-induced Ca2+ force response and a decrease in the protein content of ryanodine receptor (RYR2). These physiological and biochemical findings observed in males were not evident in female offspring. These findings illustrate a sex-specific effect of maternal NR on cardiac development, and also highlight a possible mechanism for the development of hypertension and hypertrophy in male NR offspring. PMID:26406887

  2. A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat.

    PubMed

    Krishna, Gokul; Divyashri, Gangaraju; Prapulla, S G; Muralidhara

    2015-09-01

    Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS+XOS, 3g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and ?-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota. PMID:26248513

  3. Maternal Nutrient Restriction Alters Ca2+ Handling Properties and Contractile Function of Isolated Left Ventricle Bundles in Male But Not Female Juvenile Rats.

    PubMed

    Harvey, Thomas J; Murphy, Robyn M; Morrison, Janna L; Posterino, Giuseppe S

    2015-01-01

    Intrauterine growth restriction (IUGR), defined as a birth weight below the 10th centile, may be caused by maternal undernutrition, with evidence that IUGR offspring have an increased risk of cardiovascular disease (CVD) in adulthood. Calcium ions (Ca2+) are an integral messenger for several steps associated with excitation-contraction coupling (ECC); the cascade of events from the initiation of an action potential at the surface membrane, to contraction of the cardiomyocyte. Any changes in Ca2+ storage and release from the sarcoplasmic reticulum (SR), or sensitivity of the contractile apparatus to Ca2+ may underlie the mechanism linking IUGR to an increased risk of CVD. This study aimed to explore the effects of maternal nutrient restriction on cardiac function, including Ca2+ handling by the SR and force development by the contractile apparatus. Juvenile Long Evans hooded rats born to Control (C) and nutrient restricted (NR) dams were anaesthetized for collection of the heart at 10-12 weeks of age. Left ventricular bundles from male NR offspring displayed increased maximum Ca2+-activated force, and decreased protein content of troponin I (cTnI) compared to C males. Furthermore, male NR offspring showed a reduction in rate of rise of the caffeine-induced Ca2+ force response and a decrease in the protein content of ryanodine receptor (RYR2). These physiological and biochemical findings observed in males were not evident in female offspring. These findings illustrate a sex-specific effect of maternal NR on cardiac development, and also highlight a possible mechanism for the development of hypertension and hypertrophy in male NR offspring. PMID:26406887

  4. Maternal junk-food feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring

    PubMed Central

    Ong, Z. Y.; Muhlhausler, B. S.

    2011-01-01

    Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal junk-food diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 160.6 vs. 110.8 g/kg/d; females: 191.3 vs. 130.4 g/kg/d; P<0.01). mRNA expression of ?-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.Ong, Z. Y., Muhlhausler, B. S. Maternal junk-food feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. PMID:21427213

  5. Effects of maternal calorie-restricted diet on development of the foetal heart, as evaluated in primary cultures of rat myocardial cells.

    PubMed

    Welder, A A; Grant, R; Kutschke, R L; Anthony, M; Bradlaw, J; Acosta, D

    1991-07-01

    Very-low-calorie diets have been implicated in causing ventricular arrhythmias and sudden cardiac death. Furthermore, studies indicate that maternal carbohydrate-restricted diets consumed during pregnancy and lactation reduce foetal growth, parturition and postnatal survival of rat pups. In this study, Sprague-Dawley rats were maintained on a semi-purified full-calorie or 50% carbohydrate-calorie-restricted diet throughout pregnancy. The function and integrity of myocardial cell cultures obtained from 3-5-day-old offspring from both groups of dams were evaluated after a drug-induced toxic challenge. After the myocytes had been in culture for 4 days, they were exposed to various concentrations of amitriptyline (1 x 10(-3) to 1 x 10(-5) M). Morphology, beating activity, lactate dehydrogenase release, glucose utilization, beta-adrenergic receptor [125I]iodopindolol binding, and cellular adenosine triphosphate content were evaluated for 24 hr after drug exposure. There were no significant differences in morphology, beating activity or glucose utilization between the full-calorie and calorie-restricted groups. When compared with the full-calorie group, lactate dehydrogenase release from the calorie-restricted group was significantly lower at 8 hr for the untreated controls and those cells exposed to 1 x 10(-4) and 1 x 10(-5) M-amitriptyline. Adenosine triphosphate levels were lower in untreated controls from the calorie-restricted group when compared with the full-calorie group at 4 hr. Within the calorie-restricted group, those cultures exposed to 1 x 10(-4) M-amitriptyline had significantly depressed adenosine triphosphate levels after 8 hr of drug treatment when compared with their respective untreated controls. Finally, the calorie-restricted group had significantly increased binding affinities of beta-receptors. Thus, maternal consumption of calorie-restricted diets during pregnancy may affect the myocardial functional capacity and integrity of the offspring. PMID:1654297

  6. Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

    SciTech Connect

    Kransler, Kevin M. Tonucci, David A. McGarrigle, Barbara P. Napoli, Joseph L. Olson, James R.

    2007-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 {mu}g/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis.

  7. Influence of maternal ingestion of Aroclor 1254[reg sign] (PCB) or FireMaster BP-6[reg sign] (PBB) on unstimulated and stimulated corticosterone levels in young rats

    SciTech Connect

    Meserve, L.A.; Murray, B.A.; Landis, J.A. )

    1992-05-01

    The organohalides polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) remain troublesome environmental pollutants. For example, the percentage of the population in which PCB is detectable in adipose tissue remains high. These compounds are of particular interest to residents of the North Central United States, especially in regions surrounding the Great Lakes where contaminated fish may be a regular component of the diet. Additionally, PBB was mistakenly fed to cattle and chickens in Michigan during the early 1970s, products of which were ingested by humans. Among the physiological effects of ingestion of PCB or PBB is the depression of thyroid status, which has been reported in adult humans, in adult experimental animals, and in the offspring of these animals. In adult rats, circulating levels of thyroid hormones are inversely proportional to dose of PCB or PBB in the diet. On the other hand, reports of effects of these organohalides on adrenocortical function remain equivocal, describing both PCB- and PBB-induced depression, and absence of effect in rats and monkeys. Despite the possible consequences of maternal ingestion of PCB or PBB on future generations, little work has been done previously to determine whether consumption of these materials by pregnant and lactating animals confers hypothyroidism on their offspring, and/or influences other mechanisms of endocrine control in the young. Since early studies showed that hypothyroidism induced by feeding pregnant rats the goitrogen thiouracil altered the functional capabilities in their young of the hypothalamus-pituitary-adrenal (HPA) axis, as revealed by circulating corticosterone levels, the present study was done to determine whether ingestion of either PCB (Aroclor 1254[reg sign]) or PBB (FireMaster BP-6[reg sign]) by pregnant and lactating rats resulted in depressed thyroid status and/or modified HPA axis function in their 15 day old young. 19 refs., 1 fig., 1 tab.

  8. Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and astrogliosis in the hypothalamus of the adult rat offspring.

    PubMed

    Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Peixoto-Silva, Nayara; de Oliveira, Elaine; Lisboa, Patricia C

    2015-02-14

    The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82% in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model. PMID:25609154

  9. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

    PubMed

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life. PMID:26452320

  10. Maternal deprivation in rats is associated with corticotropin releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood

    PubMed Central

    Chen, Jun; Evans, Andrew N.; Liu, Ying; Honda, Masaru; Saavedra, Juan M.; Aguilera, Greti

    2012-01-01

    Exposure to stress during early development causes long-lasting alterations in behavior and hypothalamic pituitary adrenal (HPA) axis activity, including increased expression of corticotropin releasing hormone (CRH). To determine whether early life stress causes epigenetic changes in the CRH promoter leading to increased CRH transcription, 8-week old female and male rats, subjected to maternal deprivation (MD) between days 2 and 13 post-birth, were studied for HPA axis responses to stress and CRH promoter methylation in the hypothalamic paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA). Plasma corticosterone and PVN CRH hnRNA responses to acute restraint stress were higher in MD rats of both sexes. DNA methylation analysis of the CRH promoter revealed a significantly lower percent of methylation in 2 CpGs preceding (CpG1) and inside (CpG2) the cyclic AMP-responsive element (CRE) at ?230 bp in the CRH promoter in the PVN but not the CeA of MD rats. Gel-shift assays, using nuclear proteins from forskolin treated hypothalamic 4B cells and CRH promoter CRE oligonucleotides, unmethylated or methylated at CpG1, revealed a strong band which was supershifted by phospho-CREB antibody. This band was 50% weaker using oligonucleotides methylated at CpG2 (intra-CRE), or methylated at both CpG1 and CpG2. These findings demonstrate that HPA axis hypersensitivity caused by neonatal stress causes long-lasting enhanced CRH transcriptional activity in the PVN of both sexes. Hypomethylation of the CRH promoter CRE, a region critical for CRH transcriptional activation, could serve as a mechanism for the increased transcriptional responses to stress observed in MD rats. PMID:22375940

  11. Thrifty metabolic programming in rats is induced by both maternal undernutrition and postnatal leptin treatment, but masked in the presence of both: implications for models of developmental programming

    PubMed Central

    2014-01-01

    Background Maternal undernutrition leads to an increased risk of metabolic disorders in offspring including obesity and insulin resistance, thought to be due to a programmed thrifty phenotype which is inappropriate for a subsequent richer nutritional environment. In a rat model, both male and female offspring of undernourished mothers are programmed to become obese, however postnatal leptin treatment gives discordant results between males and females. Leptin treatment is able to rescue the adverse programming effects in the female offspring of undernourished mothers, but not in their male offspring. Additionally, in these rats, postnatal leptin treatment of offspring from normally-nourished mothers programmes their male offspring to develop obesity in later life, while there is no comparable effect in their female offspring. Results We show by microarray analysis of the female liver transcriptome that both maternal undernutrition and postnatal leptin treatment independently induce a similar thrifty transcriptional programme affecting carbohydrate metabolism, amino acid metabolism and oxidative stress genes. Paradoxically, however, the combination of both stimuli restores a more normal transcriptional environment. This demonstrates that “leptin reversal” is a global phenomenon affecting all genes involved in fetal programming by maternal undernourishment and leptin treatment. The thrifty transcriptional programme was associated with pro-inflammatory markers and downregulation of adaptive immune mediators, particularly MHC class I genes, suggesting a deficit in antigen presentation in these offspring. Conclusions We propose a revised model of developmental programming reconciling the male and female observations, in which there are two competing programmes which collectively drive liver transcription. The first element is a thrifty metabolic phenotype induced by early life growth restriction independently of leptin levels. The second is a homeostatic set point calibrated in response to postnatal leptin surge, which is able to over-ride the metabolic programme. This “calibration model” for the postnatal leptin surge, if applicable in humans, may have implications for understanding responses to catch-up growth in infants. Additionally, the identification of an antigen presentation deficit associated with metabolic thriftiness may relate to a previously observed correlation between birth season (a proxy for gestational undernutrition) and infectious disease mortality in rural African communities. PMID:24447410

  12. Effect of intrauterine growth restriction on the number of cardiomyocytes in rat hearts.

    PubMed

    Corstius, Hugo Brandt; Zimanyi, Monika A; Maka, Noori; Herath, Thiloshini; Thomas, Walter; van der Laarse, Arnoud; Wreford, Nigel G; Black, M Jane

    2005-06-01

    Epidemiologic studies have linked intrauterine growth restriction (IUGR) with an increased incidence of cardiovascular disease later in life; reduced cardiomyocyte number in IUGR hearts may underlie such prenatal programming. Our aim was to examine the effect of IUGR, as a result of maternal protein restriction, on the number of cardiomyocytes in the rat heart at birth. Rats were fed either a low-protein diet (LPD) or a normal-protein diet (NPD) during pregnancy. At birth, the offspring were killed and the hearts were immersion-fixed. The number of cardiomyocyte nuclei in the hearts were stereologically determined using an optical disector-fractionator approach. In some litters, cardiomyocytes were enzymatically isolated from freshly excised hearts and the proportion of binucleated cells was determined. Taking into account the number of binucleated cells, the nuclear counts were adjusted to estimate total cardiomyocyte number. Birth weight and heart weight were significantly reduced in the LPD offspring. This was accompanied by a significant reduction in the number of cardiomyocytes per heart in the LPD offspring compared with the NPD offspring (1.18 +/- 0.05 x 10(7) and 1.41 +/- 0.06 x 10(7), respectively; p = 0.001). The number of binucleated cardiomyocytes was low (approximately 3%) and equal in both groups. In conclusion, IUGR as a result of maternal protein restriction leads to a reduction in the number of cardiomyocytes per heart. As cardiomyocyte proliferation is rare after birth, it is plausible that this reduction in cardiomyocytes may lead to compromised cardiac function later in life. PMID:15774830

  13. Can low-level ethanol exposure during pregnancy influence maternal care? An investigation using two strains of rat across two generations.

    PubMed

    Popoola, Daniel O; Borrow, Amanda P; Sanders, Julia E; Nizhnikov, Michael E; Cameron, Nicole M

    2015-09-01

    Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing an increase in offspring's tendency for alcoholism, as well as in behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17-20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with males of the same strain and treatment and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arch-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spent more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during gestation and genetic variations between strains may play an important role in the behavioral effects of prenatal manipulations. PMID:25575692

  14. Specific effects of maternal zinc depletion or repletion on the deposition of zinc and metallothionein in newborn rat livers: a longitudinal study

    SciTech Connect

    Gallant, K.R.; Cherian, M.G.

    1986-03-05

    High levels of metallothionein (MT) have been reported in association with elevated zinc (Zn) in the livers of newborn rats. Previous studies in this laboratory have demonstrated that maternal Zn-deficiency (Zn-D) specifically reduces the storage of Zn as MT in one day old pup liver. To further investigate how dietary Zn levels influence the storage of Zn as MT, newborn Zn-D pups were allowed to suckle from Zn-sufficient (Zn-S) dams and vice versa. Pups were injected with 2.5 ..mu..Ci of Zn/sup 65/ and whole body retention monitored. Pups were sacrificed at varying time periods up to weaning and hepatic levels of Zn and MT were measured. A gradual increase in the abnormally low hepatic levels of Zn and MT was observed in Zn-D pups suckling from Zn-S dams up to about day 10. Zn-S pups suckling from Zn-D dams showed a much faster rate of decline of MT and Zn than in age-matched controls, suggesting a rapid turnover of Zn-MT. Whole body retention of Zn/sup 65/ was lower in the Zn-repleted pups than in the pups which were subjected to Zn-D postnatally. These results demonstrate that the Zn-MT levels fluctuate directly in response to the Zn status of the pups, supporting the role of MT as a Zn storage protein in newborn rats.

  15. The Effect of Neonatal Leptin Antagonism in Male Rat Offspring Is Dependent upon the Interaction between Prior Maternal Nutritional Status and Post-Weaning Diet

    PubMed Central

    Beltrand, J.; Sloboda, D. M.; Connor, K. L.; Truong, M.; Vickers, M. H.

    2012-01-01

    Epidemiological and experimental studies report associations between overweight mothers and increased obesity risk in offspring. It is unclear whether neonatal leptin regulation mediates this association between overweight mothers and offspring obesity. We investigated the effect of neonatal treatment with a leptin antagonist (LA) on growth and metabolism in offspring of mothers fed either a control or a high fat diet. Wistar rats were fed either a control (CON) or a high fat diet (MHF) during pregnancy and lactation. Male CON and MHF neonates received either saline (S) or a rat-specific pegylated LA on days 3, 5, and 7. Offspring were weaned onto either a control or a high fat (hf) diet. At day 100, body composition, blood glucose, ?-hydroxybutyrate and plasma leptin and insulin were determined. In CON and MHF offspring, LA increased neonatal bodyweights compared to saline-treated offspring and was more pronounced in MHF offspring. In the post-weaning period, neonatal LA treatment decreased hf diet-induced weight gain but only in CON offspring. LA treatment induced changes in body length, fat mass, body temperature, and bone composition. Neonatal LA treatment can therefore exert effects on growth and metabolism in adulthood but is dependent upon interactions between maternal and post-weaning nutrition. PMID:22548153

  16. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

    PubMed Central

    Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

    2015-01-01

    BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

  17. Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

    PubMed Central

    Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

    2014-01-01

    Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such programmed effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood. PMID:24831231

  18. Effects of streptozotocin-induced type 1 maternal diabetes on PI3K/AKT signaling pathway in the hippocampus of rat neonates.

    PubMed

    Hami, Javad; Kerachian, Mohammad-Amin; Karimi, Razieh; Haghir, Hossein; Sadr-Nabavi, Ariane

    2016-06-01

    Diabetes in pregnancy impairs hippocampus development in offspring, leading to behavioral problems and learning deficits. Phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt) signaling pathway plays a pivotal role in the regulation of neuronal proliferation, survival and death. The present study was designed to examine the effects of maternal diabetes on PKB/Akt expression and phosphorylation in the developing rat hippocampus. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at first postnatal day (P1). The hippocampal expression and phosphorylation level of PKB/Akt, one of the key molecules in PI3K/AKT signaling pathway, was evaluated using real-time polymerase chain reaction (PCR) and western blot analysis. We found a significant bilateral downregulation of AKT1 gene expression in the hippocampus of pups born to diabetic mothers (p < 0.05). Interestingly, our results revealed a marked upregulation of Akt1 gene in insulin-treated group compared with other groups (p < 0.05). The western blot analysis also showed the reduction of phosphorylation level of all AKT isoforms in both diabetic and insulin-treated groups compared with control (p < 0.05). Moreover, the results showed a significant increase in phosphorylation level of AKT in insulin-treated group compared with the diabetic group. These results represent that diabetes during pregnancy strongly influences the regulation of PKB/AKT in the developing rat hippocampus. Furthermore, although the control of glycemia by insulin administration is not sufficient to prevent the alterations in PKB/Akt expression, it modulates the phosphorylation process, thus ultimately resulting in a situation comparable to that found in the normal condition. PMID:26479041

  19. Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring.

    PubMed

    Gugusheff, Jessica R; Bae, Sung Eun; Rao, Alexandra; Clarke, Iain J; Poston, Lucilla; Taylor, Paul D; Coen, Clive W; Muhlhausler, Beverly S

    2016-03-15

    Perinatal junk food exposure increases the preference for palatable diets in juvenile and adult rat offspring. Previous studies have implicated reduced sensitivity of the opioid pathway in the programming of food preferences; however it is not known when during development these changes in opioid signalling first emerge. This study aimed to determine the impact of a maternal junk food (JF) diet on mu-opioid receptor (MuR) expression and ligand binding in two key regions of the reward pathway, the nucleus accumbens (NAc) and the ventral tegmental area (VTA) in rats during the early suckling (postnatal day (PND) 1 and 7) and late suckling/early post-weaning (PND 21 and 28) periods. Female rats were fed either a JF or a control diet for two weeks prior to mating and throughout pregnancy and lactation. MuR expression in the VTA was significantly reduced in female JF offspring on PND 21 and 28 (by 32% and 57% respectively, P<0.05), but not at earlier time points (PND 1 and 7). MuR ligand binding was also reduced (by 22%, P<0.05) in the VTA of female JF offspring on PND 28. No effects of perinatal junk food exposure on MuR mRNA expression or binding were detected at these time points in male offspring. These findings provide evidence that the opioid signalling system is a target of developmental programming by the end of the third postnatal week in females, but not in males. PMID:26718219

  20. Effects of Post-coital Administration of Alkaloids from Senna alata (Linn. Roxb) Leaves on some Fetal and Maternal Outcomes of Pregnant Rats

    PubMed Central

    Yakubu, Musa Toyin; Musa, Isa Fakai

    2012-01-01

    Background The abortifacient claim of Senna alata (S. alata) was scientifically validated recently with alkaloids speculated to be the bioactive agent. This speculation is yet to be substantiated or refuted by scientific evidence. The present study was aimed to investigate the pregnancy terminating effects of the alkaloids from S. alata leaves. Methods Twenty four Pregnant rats (143.991.21 g) allocated randomly to four groups: A, B, C and D respectively received, 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the S. alata extracted alkaloids orally, once daily from day 10 until day 18 post-coitum. The indices of abortifacient were evaluated at the end of the exposure period. The results were analyzed by both the analysis of variance and Duncan's multiple range test and p < 0.05 was considered as statistically significant. Results Thin-layer chromatographic separation produced five spots with Rf values of 0.28, 0.33, 0.39, 0.47 and 0.55 which gave positive reaction with Meyer's and Wagner's reagents, respectively. The number of implantation sites and corpora lutea, as well as the concentrations of FSH, LH, progesterone, weight of uterus, uterine/ body weight ratio, glucose and cholesterol decreased significantly (p < 0.05) whereas the resorption index, pre- and post-implantation losses, uterine protein content and alkaline phosphatase activity increased significantly. None of the alkaloid treated animals presented with provoked vaginal opening or bleeding except fetal deaths. The alkaloid decreased the maternal weight gain, as well as feed and water intake. Conclusion Overall, the alkaloids from S. alata leaves exhibited anti-implantation, anti-gonadotropic, anti-progesteronic, embryonic resorptive, feto-maternal toxic activities but not complete abortifacient. The alkaloids alone may not be the sole abortifacient bioactive agent in the leaf extract. PMID:23926548

  1. Postnatal development in vasopressin deficient Brattleboro rats with special attention to the hypothalamo-pituitary-adrenal axis function: the role of maternal genotype.

    PubMed

    Zelena, Dra; Mergl, Zsuzsa; Makara, Gbor B

    2009-04-01

    Anomalies in hormonal and neurotransmitter status during perinatal period can lead to lifespan alterations in the central nervous system. Vasopressin is present early in the brain and has various mitogenic, metabolic and physiological actions, e.g. in water homeostasis or in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis. Therefore we examine the possible role of vasopressin in perinatal development with special attention to the influence of maternal genotype and to the HPA axis regulation. We compared homozygous vasopressin deficient (di/di) Brattleboro rats to their heterozygous (di/+) littermates both from di/+ and di/di mother. Higher locomotion due to reduced adaptation was present at preweaning. During the first 10 days of life the di/di pups from di/di mother were the smallest, while in the later perinatal period the genotype of the pups became the more important determinant of the somatic development, namely the di/di pups from both mothers had reduced weight gain. Generally the lack of vasopressin in the pups fastened the somatic development (pinna detachment, eye and ear opening, incisor eruption) however the neurobehavioral development (palmar grasp reflex, righting reflex, negative geotaxis, etc.) was not influenced profoundly by either the mother's or the pup's genotype. The lack of vasopressin in pups abolished the 24 h maternal separation induced adrenocorticotrop hormone (ACTH) elevation while the accompanying corticosterone rises were even higher. The vasopressin deficiency of the mother reduced the resting ACTH and all corticosterone levels in all pups. So we can conclude that the lack of vasopressin speeds up the development, probably there is a greater drive for self-sufficiency in these animals. The mother's vasopressin deficiency reduced the HPA axis reactivity of the pups. The role of vasopressin in the HPA axis regulation is important during the perinatal period independently from the mother's genotype. The large discrepancy between ACTH and corticosterone regulation requires further studies. PMID:19059472

  2. Long-term postpartum anxiety and depression-like behavior in mother rats subjected to maternal separation are ameliorated by palatable high fat diet.

    PubMed

    Maniam, Jayanthi; Morris, Margaret J

    2010-03-17

    While the effects of maternal separation on pups are well studied, the impact on dams has attracted little attention. The consumption of palatable food is known to dampen stress responses in animals, and emotions influence food choice in humans. Here we examined the early- and long-term impacts of maternal separation on behavioral profile of the dams, and the effects of palatable cafeteria high-fat diet (HFD). After littering, Sprague-Dawley female rats were subjected to prolonged separation, S180 (180 min) or brief separation, S15 (15 min/day) from postnatal days (PND) 2-14. At 4 weeks postpartum, half the dams were assigned to HFD. Anxiety and depression-like behaviors were assessed pre- and post-diet. Compared to S15 dams, S180 dams consuming chow demonstrated increased anxiety and depression-like behaviors assessed by elevated plus maze (EPM) and forced swim (FST) tests, respectively. These behavioral deficits were observed at 4 weeks, and persisted until 17 weeks postpartum. The S180 dams also had increased plasma corticosterone concentration compared to S15 dams, which coincided with increased hypothalamic CRH mRNA and reduced hippocampal GR mRNA expression, suggesting possible dysregulation of hypothalamic-pituitary-adrenal axis activity. Interestingly, continuous provision of HFD improved the behavioral deficits observed in S180 dams with significant reduction of hypothalamic CRH mRNA expression. These data are the first to describe long-term detrimental behavioral impacts of separation in dams, suggesting this may provide a model of postpartum depression. Moreover, they support the notion of long-term beneficial effects of 'comfort food' on stress responses. PMID:19896506

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

    PubMed

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Tsela, Smaragda; Zissis, Konstantinos M; Kalafatakis, Konstantinos; Skandali, Nikolina; Voumvourakis, Konstantinos; Carageorgiou, Haris; Tsakiris, Stylianos

    2015-08-01

    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 Mg(2+)-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 Mg(2+)-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. PMID:25123521

  4. Alterations in hepatic gene expression and genome-wide DNA methylation in rat offspring exposed to maternal obesity in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult offspring from obese (OB) rat dams gain greater body weight and fat mass than controls when fed HFD. At PND21, we examined energy expenditure (EE) (indirect calorimetry), hepatic gene expression (microarrays), and changes in genome-wide and global DNA methylation (enrichment-coupled DNA seque...

  5. Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.

    PubMed

    Latouche, Celine; Heywood, Sarah E; Henry, Sarah L; Ziemann, Mark; Lazarus, Ross; El-Osta, Assam; Armitage, James A; Kingwell, Bronwyn A

    2014-03-01

    Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt] or a normal control diet [(CD) 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt] for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 2.5 (CD) vs 56.2 6.1 (HFD) mU/L; P = 0.023]. Next-generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 0.63 (CD) vs 1.02 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of prepregnancy obesity, can promote metabolic dysregulation and predispose offspring to type 2 diabetes. PMID:24381224

  6. [Maternal phenylketonuria].

    PubMed

    Bkay, Jnos; Kiss, Erika; Simon, Erika; Sz?nyi, Lszl

    2013-05-01

    Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently. PMID:23628728

  7. Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring.

    PubMed

    Pallars, M E; Adrover, E; Imsen, M; Gonzlez, D; Fabre, B; Mesch, V; Baier, C J; Antonelli, M C

    2014-10-10

    We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain development. PMID:25130562

  8. Maternal Separation during Breastfeeding Induces Gender-Dependent Changes in Anxiety and the GABA-A Receptor Alpha-Subunit in Adult Wistar Rats

    PubMed Central

    Len Rodrguez, Diego Armando; Dueas, Zulma

    2013-01-01

    Different models of rodent maternal separation (MS) have been used to investigate long-term neurobiological and behavioral changes, associated with early stress. However, few studies have involved the analysis of sex-related differences in central anxiety modulation. This study investigated whether MS during breastfeeding affected adult males and females in terms of anxiety and brain GABA-A receptor-alpha-subunit immunoreactivity. The brain areas analyzed were the amygdale (AM), hippocampus (HP), medial prefrontal cortex (mPFC), medial preoptic area (POA) and paraventricular nucleus (PVN). Rats were housed under a reversed light/dark cycle (lights off at 7?00 h) with access to water and food ad libitum. Animals underwent MS twice daily during the dark cycle from postnatal day 1 to postnatal day 21. Behavior was tested when rats were 6570 days old using the elevated plus maze and after brains were treated for immunohistochemistry. We found that separated females spent more time in the open arms and showed more head dipping behavior compared with controls. The separated males spent more time in the center of the maze and engaged in more stretching behavior than the controls. Immunohistochemistry showed that separated females had less immunostained cells in the HP, mPFC, PVN and POA, while separated males had fewer immunolabeled cells in the PFC, PVN and AM. These results could indicate that MS has gender-specific effects on anxiety behaviors and that these effects are likely related to developmental alterations involving GABA-A neurotransmission. PMID:23826356

  9. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet.

    PubMed

    Grdebjer, Emelie M; Anderson, Stephen T; Pantaleon, Marie; Wlodek, Mary E; Moritz, Karen M

    2015-07-01

    Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague-Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (?10-25%, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex-specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5- to 1.9-fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high-fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (?2-fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health. PMID:25733565

  10. EFFECTS OF MATERNAL FOOD RESTRICTION ON FETAL LUNG EXTRACELLULAR MATRIX DEPOSITION AND LONG TERM PULMONARY FUNCTION IN AN EXPERIMENTAL RAT MODEL

    PubMed Central

    Rehan, Virender K.; Sakurai, Reiko; Li, Yishi; Karadag, Ahmet; Corral, Julia; Bellusci, Saverio; Xue, Ying Ying; Belperio, John; Torday, John S.

    2011-01-01

    Intrauterine growth restriction (IUGR) increases the risk of respiratory compromise throughout postnatal life. However, the molecular mechanism(s) underlying the respiratory compromise in offspring following IUGR is not known. We hypothesized that IUGR following maternal food restriction (MFR) would affect extracellular matrix deposition in the lung, explaining the long-term impairment in pulmonary function in the IUGR offspring. Using a well-established rat model of MFR during gestation to produce IUGR pups, we found that at postnatal day 21, and at 9 months of age the expression and abundance of elastin and alpha smooth muscle actin (αSMA), two key extracellular matrix proteins, were increased in IUGR lungs when compared to controls (p<0.05, n = 6), as determined by both Western and immunohistochemistry analyses. Compared to controls, the MFR group showed no significant change in pulmonary resistance at baseline, but did have significantly decreased pulmonary compliance at 9 months (p<0.05 vs control, n=5). In addition, MFR lungs exhibited increased responsiveness to methacholine challenge. Furthermore, exposing cultured fetal rat lung fibroblasts to serum deprivation increased the expression of elastin and elastin-related genes, which was blocked by serum albumin supplementation, suggesting protein deficiency as the predominant mechanism for increased pulmonary elastin deposition in IUGR lungs. We conclude that accompanying the changes in lung function, consistent with bronchial hyperresponsiveness, expression of the key alveolar extracellular matrix proteins elastin and αSMA increased in the IUGR lung, thus providing a potential explanation for the compromised lung function in IUGR offspring. PMID:22058072

  11. Effects of a maternal diet supplemented with chocolate and fructose beverage during gestation and lactation on rat dams and their offspring.

    PubMed

    Zhang, Zhi-Yun; Zeng, Jin-Jing; Kjaergaard, Marina; Guan, Ni; Raun, Kirsten; Nilsson, Cecilia; Wang, Ming-Wei

    2011-09-01

    1. Consumption of a high-fat and high-energy diet during pregnancy leads to a risk of long-term consequences on fetal development, as well as on the postnatal health of offspring. To investigate the effects of such a diet on fetal programming, we established a high-energy intake pregnant rat model using chocolate and fructose beverage as supplements to a normal chow diet. 2. Pregnant Sprague-Dawley rats were assigned to either chow (control) or a diet supplemented with chocolate and fructose beverage throughout gestation and lactation. The male F(1) pups received normal chow diet after weaning. Physiological or pathological changes in dams and pups (e.g. glucose and lipid metabolism) were evaluated. 3. The results showed that dams offered the high-fat (mainly from chocolate) and high-calorie diet during gestation consumed more energy and gained more weight than chow-fed dams. Over-consumption of chocolate reduced chow intake in dams, leading to low maternal protein supply. As a result, pups from these dams exhibited reduced birth weight that lasted until adulthood. The high-energy diet during lactation led to increased total body fat, as well as impaired liver function, in offspring; thus, the lactational diet is suggested to be a stronger determinant of offspring fat metabolism than gestational diet. 4. The results of the study suggest that over-supply of carbohydrates, such as chocolate and fructose, either during gestation or lactation has a negative impact on the well-being of offspring. PMID:21722163

  12. Transient suppression of late-stage neuronal progenitor cell differentiation in the hippocampal dentate gyrus of rat offspring after maternal exposure to nicotine.

    PubMed

    Ohishi, Takumi; Wang, Liyun; Akane, Hirotoshi; Shiraki, Ayako; Itahashi, Megu; Mitsumori, Kunitoshi; Shibutani, Makoto

    2014-02-01

    To examine the developmental exposure effect of nicotine (NIC) on hippocampal neurogenesis, pregnant Sprague-Dawley rats were treated with (-)-NIC hydrogen tartrate salt through drinking water at 2, 10 or 50 ppm from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, immunohistochemically doublecortin (Dcx)(+) cells increased at ≥10 ppm in the dentate subgranular zone (SGZ) as examined in male offspring; however, dihydropyrimidinase-like 3 (TUC4)(+) cells decreased at 2 ppm, and T box brain 2 (Tbr2)(+) cells were unchanged at any dose. Double immunohistochemistry revealed decreases in TUC4(+)/Dcx(+) and TUC4(+)/Dcx(-) cells, an increase in TUC4(-)/Dcx(+) cells at 2 and 10 ppm and an increase in Tbr2(-)/Dcx(+) cells at 50 ppm, suggesting an increase in type-3 progenitor cells at ≥2 ppm and decrease in immature granule cells at 2 and 10 ppm. The number of mature neuron-specific NeuN(-) progenitor cells expressing nicotinic acetylcholine receptor α7 in the SGZ and mRNA levels of Chrna7 and Chrnb2 in the dentate gyrus was unchanged at any dose, suggesting a lack of direct nicotinic stimulation on progenitor cells. In the dentate hilus, glutamic acid decarboxylase 67(+) interneurons increased at ≥10 ppm. All changes disappeared on PND 77. Therefore, maternal exposure to NIC reversibly affects hippocampal neurogenesis targeting late-stage differentiation in rat offspring. An increase in interneurons suggested that their activation affected granule cell differentiation. The lowest observed adverse effect level was at 2 ppm (0.091 mg/kg/day as a free base) by the affection of hippocampal neurogenesis at ≥2 ppm. PMID:23892646

  13. Detrimental effects of maternal lead exposure during pregnancy and lactation on molar development in the young rat.

    PubMed

    Chen, Hong-Sen; Tsai, Yu-Chen; Chen, Ker-Kong; Tseng, Yu-Chuan; Hsu, Kun-Jung

    2012-08-01

    The purpose of this animal study was to investigate the influence of maternal lead exposure during pregnancy and lactation on molar development in the offspring. Scanning electron microscopy revealed no significant differences in the molar morphology among the groups. However, in all the experimental groups, deep, wide cracks were found in the occlusal enamel. Further, the experimental groups had smaller molar diameters than the control group, lead exposure during lactation had a greater influence on the molar size in the offspring, and the groups with the higher dose of lead exposure during pregnancy and lactation had significantly smaller molar sizes than the groups that received the lower dose. The mesiodistal and buccolingual diameters of molars were measured as 3.10 0.07 and 1.95 0.04 mm for control group, 2.97 0.08 and 1.94 0.01 mm for lactation group of low dose, 2.96 0.05 and 1.84 0.02 mm for lactation group of high dose, 3.09 0.06 and 1.94 0.04 mm for pregnancy group of low dose, and 3.02 0.06 and 1.85 0.06 mm for pregnancy group of high dose, respectively. PMID:22617948

  14. Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval.

    PubMed

    Bowers, J Michael; Perez-Pouchoulen, Miguel; Edwards, N Shalon; McCarthy, Margaret M

    2013-02-20

    The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared with female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared with females and a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls. PMID:23426656

  15. Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval

    PubMed Central

    Bowers, J. Michael; Perez-Pouchoulen, Miguel; Edwards, N. Shalon; McCarthy, Margaret M.

    2013-01-01

    The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared to female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared to females and, a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls. PMID:23426656

  16. Effects of maternally exposed coloring food additives on receptor expressions related to learning and memory in rats.

    PubMed

    Ceyhan, Betul Mermi; Gultekin, Fatih; Doguc, Duygu Kumbul; Kulac, Esin

    2013-06-01

    Exposure to artificial food colors and additives (AFCAs) has been implicated in the induction and severity of some childhood behavioral and learning disabilities. N-methyl-D-aspartate receptors (NMDARs) and nicotinic acetylcholine receptors (nACHRs) are thought to be effective in the learning and memory-generating process. In this study, we investigated the effects of intrauterine exposure to AFCAs on subunit concentrations of NMDARs and nAChRs isoforms in rats. We administered a mixture of AFCAs (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation. The concentration of NR2A and NR2B subunits and nAChR ?7, ?4?2 isoforms in their offspring's hippocampi were measured by Western Blotting. Expressions of NR2B and nAChR ?2 were significantly increased (17% and 6.70%, respectively), whereas expression of nAChR ?4 was significantly decreased (5.67%) in male experimental group compared to the male control group (p<0.05). In the female experimental group, AFCAs caused a 14% decrease in NR2B expression when compared to the female control group (p<0.05). Our results indicate that exposure to AFCAs during the fetal period may lead to alterations in expressions of NMDARs and nAChRs in adulthood. These alterations were different between male and female genders. PMID:23429044

  17. Effect of exercise and protein intake during pregnancy on maternal and fetal zinc content in the Sprague-Dawley rat

    SciTech Connect

    Asente, R.A.; Cameron, S.R.; Taper, L.J.

    1986-03-05

    Pregnant Sprague-Dawley rats (179) were divided into four groups: sedentary-standard protein diet, sedentary-high protein diet, exercising-standard protein diet and exercising-high protein diet. The standard protein diet contained 24.77% protein; all other nutrients were supplied in amounts required for normal parturition. After aclimitization, the exercising dams, regardless of diet, were forced to swim continuously for one and one-half hours/day until sacrifice. The four major groups were further subdivided into 28 groups, designated by three-day intervals according to gestational day - days 3, 6, 9, 12, 15, 18 and 21. Uterine tissues were analyzed for zinc; fetal and placental tissues were separated from uterine tissue for days 15 through 21 only. Uterine zinc was affected solely by gestation; absolute placental zinc values were lowest in the sedentary-high and exercising-low protein groups, while the exercising-high protein group possessed the greatest. No significant difference was detected in fetal zinc concentrations. Fetal tissues from exercising dams weighed significantly less than fetal tissue from the sedentary dams; and sedentary-high protein dams produced significantly more fetuses than the exercising-high protein dams. Both protein intake and exercise significantly affect normal parturition and zinc metabolism in the rat.

  18. THE TSC COMPLEX IS REQUIRED FOR THE BENEFITS OF DIETARY PROTEIN RESTRICTION ON STRESS RESISTANCE IN VIVO

    PubMed Central

    Harputlugil, Eylul; Hine, Christopher; Vargas, Dorathy; Robertson, Lauren; Manning, Brendan D.; Mitchell, James R.

    2014-01-01

    SUMMARY Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repressor TSC complex. However, while GCN2 was dispensable for PR-induced protection, hepatic TSC1 was required. PR improved hepatic insulin sensitivity in a TSC1-dependent manner prior to ischemia, facilitating increased pro-survival signaling and reduced apoptosis after reperfusion. These benefits were partially abrogated by pharmacological PI3K inhibition or genetic deletion of the insulin receptor in hepatocytes. In conclusion, improved insulin sensitivity upon short-term PR required TSC1, facilitated increased pro-survival signaling after injury, and contributed partially to PR-mediated resistance to clinically relevant ischemia reperfusion injury. PMID:25131199

  19. Changes in Maternal liver Cyp2c and Cyp2d Expression and Activity During Rat Pregnancy

    PubMed Central

    Dickmann, Leslie J.; Tay, Suzanne; Senn, Tauri D.; Zhang, Huixia; Visone, Anthony; Unadkat, Jashvant D.; Hebert, Mary F.; Isoherranen, Nina

    2009-01-01

    During human pregnancy, CYP2C9, CYP2C19, and CYP2D6 activities are altered. The aim of the current study was to determine if this phenomenon can be replicated in the rat, and to evaluate the mechanisms that contribute to the changes in Cyp2c and Cyp2d activity during pregnancy. The intrinsic clearance of dextromethorphan O-demethylation, a measure of Cyp2d2 activity, was decreased 80% at both days 9 and 19 of gestation when compared to nonpregnant controls. The decreased intrinsic clearance was a result of both decreased Vmax and increased Km -values at both days of gestation. Quantitative RT-PCR revealed that transcripts of Cyp2d2 and Cyp2d4 were significantly decreased at day 19 of pregnancy (p<0.05) when compared to day 9 and nonpregnant controls. The decrease in Cyp2d mRNA levels correlated with a decrease in several nuclear receptor mRNA levels (RAR?, RXR?, HNF1 and HNF3?) but not with the mRNA levels of nuclear receptors usually associated with regulation of P450 enzymes (PXR, CAR and HNF4?). In contrast, Cyp2c12 and Cyp2c6 transcription and protein expression were not significantly altered during rat pregnancy although the intrinsic clearance of Cyp2c6-mediated diclofenac 4?-hydroxylation was increased 2-fold on day 19 of gestation when compared to nonpregnant controls. The increase in intrinsic clearance was due to a decrease in the Km-value for 4?-hydroxydiclofenac formation. These data show that pregnancy significantly alters the expression and activity of drug metabolizing enzymes in an enzyme and gestational stage specific manner. These changes are likely to have toxicological and therapeutic implications. PMID:18342837

  20. Maternal immunization.

    PubMed

    Chu, Helen Y; Englund, Janet A

    2014-08-15

    Maternal immunization has the potential to protect the pregnant woman, fetus, and infant from vaccine-preventable diseases. Maternal immunoglobulin G is actively transported across the placenta, providing passive immunity to the neonate and infant prior to the infant's ability to respond to vaccines. Currently inactivated influenza, tetanus toxoid, and acellular pertussis vaccines are recommended during pregnancy. Several other vaccines have been studied in pregnancy and found to be safe and immunogenic and to provide antibody to infants. These include pneumococcus, group B Streptococcus, Haemophilus influenzae type b, and meningococcus vaccines. Other vaccines in development for potential maternal immunization include respiratory syncytial virus, herpes simplex virus, and cytomegalovirus vaccines. PMID:24799324

  1. Maternal Immunization

    PubMed Central

    Chu, Helen Y.; Englund, Janet A.

    2014-01-01

    Maternal immunization has the potential to protect the pregnant woman, fetus, and infant from vaccine-preventable diseases. Maternal immunoglobulin G is actively transported across the placenta, providing passive immunity to the neonate and infant prior to the infant's ability to respond to vaccines. Currently inactivated influenza, tetanus toxoid, and acellular pertussis vaccines are recommended during pregnancy. Several other vaccines have been studied in pregnancy and found to be safe and immunogenic and to provide antibody to infants. These include pneumococcus, group B Streptococcus, Haemophilus influenzae type b, and meningococcus vaccines. Other vaccines in development for potential maternal immunization include respiratory syncytial virus, herpes simplex virus, and cytomegalovirus vaccines. PMID:24799324

  2. Maternal phenylketonuria.

    PubMed

    Davidson, D C

    1989-01-01

    The exact mechanism of fetal damage in maternal phenylketonuria (PKU) is uncertain and although the fetus is heterozygotic for the gene coding for phenylalanine hydroxylase its immature hepatic enzyme system may be the reason for its inability to deal adequately with transplacental phenylalanine uptake. Several aspects of the management of maternal PKU are discussed and several case studies are presented. Dietary treatment should begin preconceptually despite evidence that post-conceptual treatment can have an acceptable outcome. Maternal recognition of the need for pre-conceptual treatment should increase with improvements in intellectual abilities of PKU girls resulting from neonatal screening and appropriate dietary management. PMID:2622813

  3. Effect in rats of simultaneous prenatal exposure to ochratoxin A and aflatoxin B1. I. Maternal toxicity and fetal malformations.

    PubMed

    Wangikar, P B; Dwivedi, P; Sinha, Neeraj

    2004-12-01

    Ochratoxin A (OA) and Aflatoxin B1 (AFB1), the food borne mycotoxins are produced by several fungal species of the genera Aspergillus and Penicillium. To determine the teratogenic effects, these mycotoxins were administered orally either individually or in combination to the pregnant Wistar rats on days 6-15 of gestation. OA and AFB1 were dissolved in corn oil and different doses of OA (0.125, 0.25, 0.50, and 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, and 1.00 mg/kg), and a combination of OA+AFB1 (0.125+0.125; 0.25+0.50; 0.50+0.25 mg/kg) were given by gastric intubation to rats. During dosing period, the body weight and body weight gains significantly decreased at a higher dosage, in both individual and combined treatments. In all the combination treatments, the percent implants resorbed, fetal body weights, and crown-rump lengths were comparable to those of controls and with the individual mycotoxin treatment. The number of dead fetuses was significantly increased in the high OA combination (OA+AFB1 0.50+0.25) group as compared with the other two combinations. OA and AFB1 alone and in combination caused various gross, skeletal, and visceral anomalies. The occurrence was considerably less pronounced in fetuses of AFB1 and combination groups as compared with those of OA group fetuses. The exencephaly, incomplete closure of skull, wavy and fused ribs, agenesis of the ischium bone, and enlarged renal pelvis, recorded in OA treatment and ear abnormality and incomplete ossification of skull bones observed in AFB1 when given individually, were not seen in combination groups. However, new manifestations, such as gastroschisis and syndactyly were observed and the incidence of cardiac defects was increased in fetuses due to the combined treatment. The results of the present study indicated that there is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1. Apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards. PMID:15617020

  4. Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring.

    PubMed

    Pinheiro, C R; Moura, E G; Manhes, A C; Fraga, M C; Claudio-Neto, S; Younes-Rapozo, V; Santos-Silva, A P; Lotufo, B M; Oliveira, E; Lisboa, P C

    2015-10-01

    The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus. PMID:26048299

  5. Maternal intake of Omega-3 essential fatty acids improves long term potentiation in the dentate gyrus and Morris water maze performance in rats.

    PubMed

    Kavraal, Sehrazat; Oncu, Sena Kara; Bitiktas, Soner; Artis, A Seda; Dolu, Nazan; Gunes, Tamer; Suer, Cem

    2012-10-30

    Omega-3 fatty acid deprivation during development reduces performance in learning tasks, and dietary DHA supplementation improves learning ability and enhances long term memory in both young and old animals. However, little attention has been paid to the effect of maternal intake of Omega-3 fatty acids on hippocampal function in their pups. Randomly some of the pregnant dams were supplemented with Omega-3 essential fatty acid, others with tap-water, during pregnancy and breast-feeding by gavage daily. Spatial learning and memory was tested in Morris water maze. Field potentials from the dentate gyrus were recorded in response to medial perforant pathway in urethane-anesthetized pups. Omega-3-treated rats found the platform less traveled and closer to platform than control animals. However the pups from both groups show the same performance in retrieval task. No differences were found between corresponding animal groups in the input-output curves of the field potential slopes, suggesting no effect of Omega-3 supplementation on basal synaptic efficacy. Potentiation of population spike amplitude was much higher in pups of Omega-3 treated dams than control. Up to now Omega 3 fatty acid has been shown to be beneficial on the synaptic plasticity only under some pathological conditions. For the first time, we showed improved dentate gyrus-LTP and enhanced Morris water maze performance in healthy pups from healthy dams treated with Omega-3 fatty acids during pregnancy and breast-feeding period. Molecular studies are needed to explain Omega-3 effect on hippocampal synaptic plasticity. PMID:22981414

  6. Short- and long-term effects of maternal perinatal undernutrition are lowered by cross-fostering during lactation in the male rat.

    PubMed

    Wattez, J-S; Delahaye, F; Barella, L F; Dickes-Coopman, A; Montel, V; Breton, C; Mathias, P; Folign, B; Lesage, J; Vieau, D

    2014-04-01

    Undernutrition exposure during the perinatal period reduces the growth kinetic of the offspring and sensitizes it to the development of chronic adult metabolic diseases both in animals and in humans. Previous studies have demonstrated that a 50% maternal food restriction performed during the last week of gestation and during lactation has both short- and long-term consequences in the male rat offspring. Pups from undernourished mothers present a decreased intrauterine (IUGR) and extrauterine growth restriction. This is associated with a drastic reduction in their leptin plasma levels during lactation, and exhibit programming of their stress neuroendocrine systems (corticotroph axis and sympatho-adrenal system) in adulthood. In this study, we report that perinatally undernourished 6-month-old adult animals demonstrated increased leptinemia (at PND200), blood pressure (at PND180), food intake (from PND28 to PND168), locomotor activity (PND187) and altered regulation of glycemia (PND193). Cross-fostering experiments indicate that these alterations were prevented in IUGR offspring nursed by control mothers during lactation. Interestingly, the nutritional status of mothers during lactation (ad libitum feeding v. undernutrition) dictates the leptin plasma levels in pups, consistent with decreased leptin concentration in the milk of mothers subjected to perinatal undernutrition. As it has been reported that postnatal leptin levels in rodent neonates may have long-term metabolic consequences, restoration of plasma leptin levels in pups during lactation may contribute to the beneficial effects of cross-fostering IUGR offspring to control mothers. Collectively, our data suggest that modification of milk components may offer new therapeutic perspectives to prevent the programming of adult diseases in offspring from perinatally undernourished mothers. PMID:24847697

  7. Assessment of the Protective Role of Prenatal Zinc versus Insulin Supplementation on Fetal Cardiac Damage Induced by Maternal Diabetes in Rat Using Caspase-3 and KI67 Immunohistochemical Stains

    PubMed Central

    Shams, Ahmed S.; Mohammed, Mona H.; Loka, Mona M.; Abdel Rahman, Gamal M.

    2016-01-01

    Maternal diabetes mellitus (DM) affects early organogenesis. Metabolic disorders of DM are associated with a depleted zinc status. This study evaluated the effect of maternal DM on cardiac development of rat fetuses and protective roles of prenatal zinc versus insulin supplementation. Pregnant rats were divided into 4 groups ((I) control, (II) STZ-induced DM, (III) STZ-induced DM treated with Zn, and (IV) STZ induced DM treated with insulin), all sacrificed on GD 20. Fetal heart weight of diabetic rats showed significant decrease compared to controls (P < 0.05). H&E stained section of controls had normal appearance of the myocardium, compared to diabetics that showed myocardial disarray with characteristic degenerative changes. Sections of zinc treated group showed restored architecture of normal myofibrils with minimal degenerative changes, while those of insulin treated group show partial restoration of the normal architecture of cardiomyocytes with focal improvement of cardiac tissue. Caspase-3 immunostained slides showed positive cytoplasmic immunoreactivity in diabetic group. But KI67 immunostained slides revealed negative nuclear immunoreaction in diabetics. We observed that gestational diabetes was associated with increased risk of fetal myocardial damage that might be caused by increased apoptotic level. Treating diabetic pregnant subjects with zinc and insulin was associated with improvement in myocardial integrity. PMID:26925289

  8. Maternal guilt.

    PubMed

    Rotkirch, Anna; Janhunen, Kristiina

    2010-01-01

    The recent emphasis on humans as cooperative breeders invites new research on human family dynamics. In this paper we look at maternal guilt as a consequence of conditional maternal investment. Solicited texts written by Finnish mothers with under school-aged children in 2007 (n = 63) described maternal emotions perceived as difficult and forbidden. Content analysis of guilt-inducing situations showed that guilt arose from diverging interest and negotiations between the mother and child (i.e., classic parent- offspring conflict). Also cultural expectations of extensive and perpetual high-quality maternal investment or the "motherhood myth" induced guilt in mothers. We argue that guilt plays an important role in maternal-investment regulation. Maternal guilt is predicted to vary with social and cultural context but also to show universal characteristics due to parent-offspring conflict and allomaternal manipulation. Results are preliminary and intended to stimulate research into the mechanisms, gender differences and cultural variations of guilt and other social emotions in human parenting. PMID:22947781

  9. Maternal supplementation with citrulline increases renal nitric oxide in young spontaneously hypertensive rats and has long-term antihypertensive effects.

    PubMed

    Koeners, Maarten P; van Faassen, Ernst E; Wesseling, Sebastiaan; de Sain-van der Velden, Monique; Koomans, Hein A; Braam, Branko; Joles, Jaap A

    2007-12-01

    NO deficiency is associated with development of hypertension. Defects in the renal citrulline-arginine pathway or arginine reabsorption potentially reduce renal NO in prehypertensive spontaneously hypertensive rats (SHRs). Hence, we investigated genes related to the citrulline-arginine pathway or arginine reabsorption, amino acid pools, and renal NO in 2-week-old prehypertensive SHRs. In addition, because perinatally supporting NO availability reduces blood pressure in SHRs, we supplemented SHR dams during pregnancy and lactation with citrulline, the rate-limiting amino acid for arginine synthesis. In female offspring, gene expression of argininosuccinate synthase (involved in renal arginine synthesis) and renal cationic amino acid Y-transporter (involved in arginine reabsorption) were both decreased in 2-day and 2-week SHRs compared with normotensive WKY, although no abnormalities in amino acid pools were observed. In addition, 2-week-old female SHRs had much less NO in their kidneys (0.46+/-0.01 versus 0.68+/-0.05 nmol/g of kidney weight, respectively; P<0.001) but not in their heart. Furthermore, perinatal supplementation with citrulline increased renal NO to 0.59+/-0.02 nmol/g of kidney weight (P<0.001) at 2 weeks and persistently ameliorated the development of hypertension in females and until 20 weeks in male SHR offspring. Defects in both the renal citrulline-arginine pathway and in arginine reabsorption precede hypertension in SHRs. We propose that the reduced cationic amino acid transporter disables the developing SHR kidney to use arginine reabsorption to compensate for reduced arginine synthesis, resulting in organ-specific NO deficiency. This early renal deficiency and its adverse sequels can be corrected by perinatal citrulline supplementation persistently in female and transiently in male SHRs. PMID:17938381

  10. ROLE OF METALLOTHIONEIN INDUCTION AND ALTERED ZINC STATUS AS MATERNAL MEDIATORS OF DEVELOPMENTAL TOXICITY IN RATS: COMPARISON OF THE EFFECTS OF URETHANE AND STYRENE

    EPA Science Inventory

    We hypothesize that maternal metallothionein (MT) induction by toxic dosages of chemicals may contribute to or cause developmental toxicity by the following chain of events: ) maternal hepatic MT induction; 2) redistribution of Zn to the newly synthesized MT; 3) decreased circula...

  11. Maternal low protein diet reduces birth weight and increases brown adipose tissue UCP-1 and FNDC5 gene expression in male neonatal Sprague-Dawley rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  12. SISTER-CHROMATID EXCHANGE INDUCTION IN RAT MATERNAL, EMBRYONIC AND EXTRA-EMBRYONIC CELLS AFTER IN VIVO EXPOSURE TO 4-NITROQUINOLINE 1-OXIDE

    EPA Science Inventory

    Genetic damage is associated with various embryo pathologies; and many teratogens and transplacental carcinogens are known to be genotoxic. The present study was aimed at charaterizing SCE induction levels in rodent maternal, embryonic and extra-embryonic cells after maternal exp...

  13. Maternal low protein diet-induced low birth weight in male, neonate Sprague-Dawley rats is mediated by altered brown adipose tissue thermogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  14. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The proportion of obese women who become pregnant continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are matern...

  15. Effects of meal-time feeding and protein restriction on walking ability and some bone and carcass properties in broilers.

    PubMed

    Konca, Y; Yaylak, E; Onen, A

    2008-09-01

    This experiment was designed to investigate the effects of meal-time feeding and protein restriction on performance, gait score (GS) and carcass and bone traits in broilers. A total of 420 1-day-old chicks were wing banded and randomly distributed into 21 pens with 20 chicks each. At 7 days of age, chicks were weighed and randomly assigned to one of the three treatments: (1) control (C) feed (23.02% crude protein (CP)) was available ad libitum; (2) meal-time feeding (MF); control feed was available from 0100 to 0900 h and from 1500 to 2300 h. Food was withdrawn from 0900 to 1500 h and whole wheat (10 g/bird per day) was dispersed on the floor from 7 to 21 days; and (3) low-protein (LP) diet (19.71% CP) was fed to the chicks from 7 to 21 days. All of the groups were fed ad libitum from 1 to 7 days of age and from 21 to 45 days of age with a standard commercial diet. Individual body weight was measured on days 7, 21 and 45. Feed consumption was measured from 7 to 21 days and from 21 to 45 days. Forty-two chicks were humanly slaughtered and eviscerated for bone evaluation, on days 21 and 45. Also carcass characteristics were determined on day 45. Control group body weight was significantly higher (P < 0.05) at 21 and 45 days of age than the MF and LP groups, which did not differ. Feed intake was reduced by meal-time feeding and LP diet (P < 0.01). Feed efficiency was the best in the MF group during the period of 21 to 45 days of age (P < 0.01). In the control group, shank was significantly longer than that of the LP group and tibia breaking strength was higher than that of the MF group at 21 days (P < 0.05). However, shank width, tibia wet weight and tibia mid-diaphysis ash percentage of the MF group were significantly lower than those of the C and LP groups at 21 days of age (P < 0.05). GS, shank and carcass and tibia bone traits on day 45 were not significant among groups. No compensatory growth and walking ability improvement were observed at 45 days of age for broilers fed with MF and LP between 7 and 21 days of age. PMID:22443821

  16. Transcriptome analysis of porcine M. semimembranosus divergent in intramuscular fat as a consequence of dietary protein restriction

    PubMed Central

    2013-01-01

    Background Intramuscular fat (IMF) content is positively correlated with aspects of pork palatability, including flavour, juiciness and overall acceptability. The ratio of energy to protein in the finishing diet of growing pigs can impact on IMF content with consequences for pork quality. The objective of this study was to compare gene expression profiles of Musculus semimembranosus (SM) of animals divergent for IMF as a consequence of protein dietary restriction in an isocaloric diet. The animal model was derived through the imposition of low or high protein diets during the finisher stage in Duroc gilts. RNA was extracted from post mortem SM tissue, processed and hybridised to Affymetrix porcine GeneChip arrays. Results IMF content of SM muscle was increased on the low protein diet (3.60??0.38% versus 1.92??0.35%). Backfat depth was also greater in animals on the low protein diet, and average daily gain and feed conversion ratio were lower, but muscle depth, protein content and moisture content were not affected. A total of 542 annotated genes were differentially expressed (DE) between animals on low and high protein diets, with 351 down-regulated and 191 up-regulated on the low protein diet. Transcript differences were validated for a subset of DE genes by qPCR. Alterations in functions related to cell cycle, muscle growth, extracellular matrix organisation, collagen development, lipogenesis and lipolysis, were observed. Expression of adipokines including LEP, TNF? and HIF1? were increased and the hypoxic stress response was induced. Many of the identified transcriptomic responses have also been observed in genetic and fetal programming models of differential IMF accumulation, indicating they may be robust biological indicators of IMF content. Conclusion An extensive perturbation of overall energy metabolism in muscle occurs in response to protein restriction. A low protein diet can modulate IMF content of the SM by altering gene pathways involved in lipid biosynthesis and degradation; however this nutritional challenge negatively impacts protein synthesis pathways, with potential consequences for growth. PMID:23829541

  17. Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to Poly IC

    PubMed Central

    Vorhees, Charles V.; Graham, Devon L.; Braun, Amanda A.; Schaefer, Tori L.; Skelton, Matthew R.; Richtand, Neil M.; Williams, Michael T.

    2012-01-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero-maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, acoustic startle, or latent inhibition deficits reported in Poly IC-treated rats, but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). PMID:22473973

  18. Expression of genes encoding enzymes involved in the one carbon cycle in rat placenta is determined by maternal micronutrients (folic acid, vitamin B12) and omega-3 fatty acids.

    PubMed

    Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2014-01-01

    We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. PMID:25003120

  19. Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12) and Omega-3 Fatty Acids

    PubMed Central

    Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2014-01-01

    We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. PMID:25003120

  20. A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance.

    PubMed

    Pannia, Emanuela; Cho, Clara E; Kubant, Ruslan; Snchez-Hernndez, Diana; Huot, Pedro S P; Chatterjee, Diptendu; Fleming, Alison; Anderson, G Harvey

    2015-02-01

    High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-? in adipose and -? in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance. PMID:25264184

  1. Brief and long periods of maternal separation affect maternal behavior and offspring behavioral development in C57BL/6 mice.

    PubMed

    Bailoo, Jeremy D; Jordan, Richard L; Garza, Xavier J; Tyler, Amber N

    2014-05-01

    For rats, maternal mediation of brief and longer term dam-pup separations were thought to account for pup differences in adult "emotionality." In this study, early handling (EH), maternal separation (MS), and maternal peer separation (MPS) groups were compared to an animal facility reared (AFR) group for maternal behavior and offspring adult open-field behavior in C57BL/6 mice. Although MS and MPS dams displayed higher levels of maternal behavior upon reunion, these group differences did not predict offspring open-field behavior. However, when offspring behavior was analyzed as a function of specific aspects of maternal behavior, irrespective of treatment group, pups that received high levels of quiescent nursing and activity, but not licking, were less "emotional." Individual differences in maternal licking of pups predicted variability of "emotional" behavior for AFR and EH pups. Thus, for this strain of mouse, individual and not treatment differences in maternal care predict offspring "emotional" development. PMID:23775283

  2. Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function.

    PubMed

    Connor, K L; Vickers, M H; Beltrand, J; Meaney, M J; Sloboda, D M

    2012-05-01

    We have previously reported that offspring of mothers fed a high fat (HF) diet during pregnancy and lactation enter puberty early and are hyperleptinaemic, hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also impact offspring development and disease risk.We therefore hypothesized that prenatal nutrition would affect maternal care and that an interaction may exist between a maternal HF diet and maternal care, subsequently impacting on offspring phenotype.Wistar rats were mated and randomized to control dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Maternal care was assessed by observing maternal licking and grooming of pups between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a control (con) or HF (hf) diet. From P27, pubertal onset was assessed. At ?P105 oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF-fed mothers licked and groomed pups less than CON dams.Maternal fat:lean ratio was higher in HF dams at weaning and was associated with higher maternal plasma leptin and insulin concentrations, but there was no effect of maternal care on fat:lean ratio or maternal hormone levels. Both female and male offspring of HF dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF offspring were heavier than controls. Prepubertal retroperitoneal fat mass was greater in pups from HF-fed dams compared to CON and was associated with elevated circulating leptin concentrations in females only, but there was neither an effect of maternal care, nor an interaction between maternal diet and care on prepubertal fat mass. Pups from HF-fed dams went into puberty early and this effect was exacerbated by a postweaning HF diet.Maternal and postweaning HF diets independently altered oestrous cyclicity in females: female offspring of HF-fed mothers were more likely to have prolonged or persistent oestrus, whilst female offspring fed a HF diet postweaning were more likely to have irregular oestrous cycles and were more likely to have prolonged or persistent oestrus. These data indicate that maternal HF nutrition during pregnancy and lactation results in a maternal obese phenotype and has significant impact on maternal care during lactation. Maternal and postweaning nutritional signals, independent of maternal care, alter offspring body fat pre-puberty and female reproductive function in adulthood, which may be associated with advanced ovarian ageing and altered fertility. PMID:22411006

  3. Reproductive and Developmental Toxicity of Orally Administered Botanical Composition, UP446-Part II: Effects on Prenatal and Postnatal Development, Including Maternal Function in Sprague-Dawley Rats.

    PubMed

    Yimam, Mesfin; Lee, Young-Chul; Hyun, Eu-Jin; Jia, Qi

    2015-08-01

    Almost all herbal remedies could be therapeutic at one dose and toxic at another. These facts become more troubling and a double threat when uncharacterized medicinal herbs are bl