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Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.  


Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1?, UCP3 and PPAR? and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco



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

PubMed Central

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.

Torres, Nimbe; Bautista, Claudia J.; Tovar, Armando R.; Ordaz, Guillermo; Rodriguez-Cruz, Maricela; Ortiz, Victor; Granados, Omar; Nathanielsz, Peter W.; Larrea, Fernando



Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid  

PubMed Central

A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.

Stupka, Elia; Clark, Adrian J. L.; Langley-Evans, Simon



Maternal protein restriction alters VEGF signaling and decreases pulmonary alveolar in fetal rats  

PubMed Central

Epidemiological studies have demonstrated that intrauterine growth restriction (IUGR) increases the risk for respiratory morbidity from infancy, throughout childhood and into adulthood. Chronic restriction of nutrients causes abnormalities in the airways and lungs of offspring, but whether IUGR adversely impacts fetal pulmonary vascular development and underlying mechanisms remain under investigation. In this study, we investigated the effects of protein malnutrition in utero on pulmonary alveolarization and vascular growth of the fetal lung and placentae. Pregnant rats were feed with an isocaloric low-protein diet (8% protein) until delivery. Placenta and fetal lungs were harvested on 20th day of gestation (term 21 days of gestation). Lung index (lung weight as a percentage of body weight), total DNA and protein, radial alveolar count, arteriolar wall thickness, lung maturity and angiogenic factor VEGF were assessed. The lung was hypoplastic in IUGR fetus, evidenced by reduction in lung weight, DNA and protein content. Protein restriction in utero led to higher glycogen levels, but reduced number of alveoli as confirmed by the measurement of radial alveolar counts. IUGR fetus had significantly reduced VEGF, Flk-1 levels in lung but no changes in Flt-1 mRNA. Furthermore, IUGR was associated with increased lung miR-126-3p levels, which modulated the expression of angiogenic factor. In contrast, with regard to the placenta, IUGR fetus presented with decreased expression of VEGF, with no changes in VEGF receptors and expression-regulating miRNAs. This work suggested that VEGF signaling defect plays an important role in the defective lung development, which may explain the increased incidence of respiratory infections in IUGR patients.

Liu, Xiaomei; Lin, Yan; Tian, Baoling; Miao, Jianing; Xi, Chunyan; Liu, Caixia



Programming of adult blood pressure by maternal protein restriction: Role of nephrogenesis  

Microsoft Academic Search

Programming of adult blood pressure by maternal protein restriction: Role of nephrogenesis.BackgroundModest maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult male but not female offspring. This study determined whether a more severe protein restriction has equivalent effects on male and female rat offspring, and examined the role of nephrogenesis in this programming.MethodsSprague-Dawley rats were

Lori L. Woods; RUTH RASCH



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

Microsoft Academic Search

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')

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



Maternal Protein Restriction Affects Postnatal Growth and the Expression of Key Proteins Involved in Lifespan Regulation in Mice  

Microsoft Academic Search

We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the

Jian-Hua Chen; Malgorzata S. Martin-Gronert; Jane Tarry-Adkins; Susan E. Ozanne; Silvana Gaetani



Intrauterine programming of fetal islet gene expression in rats—effects of maternal protein restriction during gestation revealed by proteome analysis  

Microsoft Academic Search

Aims\\/hypothesis  Fetal undernutrition can result in intrauterine growth restriction and increased incidence of Type 2 diabetes mellitus. Intrauterine malnutrition in form of an isocaloric low-protein diet given to female rats throughout gestation decreases islet-cell proliferation, islet size and pancreatic insulin content, while increasing the apoptotic rate and sensitivity to nitrogen oxide and interleukin-1. Hence, the influence of a low-protein diet on

T. Sparre; B. Reusens; H. Cherif; M. R. Larsen; P. Roepstorff; S. J. Fey; P. Mose Larsen; C. Remacle; J. Nerup



Cardiac responses of rats submitted to postnatal protein restriction.  


Undernutrition during critical stages of development and childhood has important effects on cardiovascular homeostasis. The present study was undertaken to evaluate the in vivo and ex vivo cardiac function of rats submitted to postnatal protein restriction. Male Wistar rats (28 days old) were fed a regular (20%) or low-protein (6%) diet over 5 weeks. After this period, cardiac function was analyzed by echocardiography and isolated heart preparation. Furthermore, the density of cardiac noradrenergic fibers and hematological profile were evaluated. We found that malnourished rats exhibited elevated arterial blood pressure, increased fractional shortening (echocardiography), increased systolic tension, increased ±dT/dt (isolated heart technique), impaired diastolic function characterized by a slight increase in the left ventricular end-diastolic diameter (echocardiography) and decreased diastolic tension (isolated heart technique), and cardiac hypertrophy evidenced by augmentation of the posterior left ventricular wall and discrete hematological changes. In addition, malnourished rats exhibited increased noradrenergic fiber density in their hearts (0.08% ± 0.02% area in control rats vs. 0.17% ± 0.03% area in malnourished rats). Our current data demonstrate that postnatal protein restriction causes cardiac adaptation characterized by an early overworking heart. This is at least in part mediated by an increase in the efferent sympathetic fibers to the heart. These findings provide important information for efforts to prevent and manage the consequences of undernutrition in the human population. PMID:22497279

Murça, Tatiane Moisés; Magno, Tatiana Soares Dos Reis; De Maria, Marilda Luz de Andrade; Capuruço, Carolina Andrade Bragança; Chianca, Deoclécio Alves; Ferreira, Anderson José



Gestational protein restriction induces alterations in placental morphology and mitochondrial function in rats during late pregnancy.  


The placenta acts a regulator of nutrient composition and supply from mother to fetus and is the source of hormonal signals that affect maternal and fetal metabolism. Thus, appropriate development of the placenta is crucial for normal fetal development. We investigated the effect of gestational protein restriction (GPR) on placental morphology and mitochondrial function on day 19 of gestation. Pregnant dams were divided into two groups: normal (NP 17 % casein) or low-protein diet (LP 6 % casein). The placentas were processed for biochemical, histomorphometric and ultrastructural analysis. The integrity of rat placental mitochondria (RPM) isolated by conventional differential centrifugation was measured by oxygen uptake (Clark-type electrode). LP animals presented an increase in adipose tissue and triacylglycerol and a decrease in serum insulin levels. No alterations were observed in body, liver, fetus, or placenta weight. There was also no change in serum glucose, total protein, or lipid content. Gestational protein restriction had tissue-specific respiratory effects, with the observation of a small change in liver respiration (~13 %) and considerable respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by RPM in the LP groups suggests uncoupling between respiration and oxidative phosphorylation. In addition, ultrastructural analysis of junctional zone giant cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of most organelles and intense vacuolization. The present results led us to hypothesize that GPR alters placental structure and morphology, induces sensitivity to insulin, mitochondrial abnormalities and suggests premature aging of the placenta. Further studies are needed to test this hypothesis. PMID:23884563

Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Moraes, Camila; Amaral, Maria Esmeria Corezola; Catisti, Rosana



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

PubMed Central

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.

Das, Kusal K; Dasgupta, Shakuntala



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

PubMed Central

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 7–10 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.

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



Effects of oxidative stress on vascular reactivity in the offspring of protein-restricted stroke-prone spontaneously hypertensive rats.  


Oxidative stress was induced in 12-week-old offspring of protein-restricted (9% protein) and control (20% protein) protein-restricted stroke-prone spontaneously hypertensive rats (SHRSP) by administering phorbol 12-myristate 13-acetate (PMA) for 4 weeks to determine the effects of oxidative stress on the vascular function of the SHRSP offspring. There was no significant difference in the blood pressure of offspring of the protein-restricted dams and control dams. The plasma diacron-reactive oxygen metabolite (dROM) level at 16 weeks of age was significantly higher in offspring of the protein-restricted dams, whereas the anti-oxidative enzyme activity was similar in both groups. Acetylcholine (Ach)-induced relaxation was significantly reduced in offspring of the protein-restricted dams. The expression of endothelial nitric oxide synthase (eNOS) was lower and the expression of soluble guanylic acid cyclase (sGC) was higher in offspring of the protein-restricted dams. These results indicate that SHRSP offspring of the protein-restricted dams were sensitive to oxidative stress, and displayed the vascular dysfunction. PMID:23924731

Takemori, Kumiko; Tahara, Aki; Murakami, Tetsuo; Kometani, Takashi



Protein restriction does not impair adaptations induced in cardiomyocytes by exercise in rats.  


The effect of a treadmill running program on physical performance and morphofunctional adaptations was investigated in control and malnourished rats. Male 4-week old Wistar rats were randomized in groups of 12 animals: control trained (CT), control sedentary (CS), malnourished trained (MT) and malnourished sedentary (MS). Control and malnourished animals received chow with 12% protein or 6% protein, respectively. Trained groups were subjected to a treadmill running program for 8 weeks. Physical performance, biochemical parameters, cardiomyocytes morphology and biomechanics were determined. Malnourished animals presented reduction in body mass, serum levels of total protein, albumin and hemoglobin compared to the control groups. At 1 and 3 Hz cardiomyocytes from CT and MT showed higher cell shortening, speed of contraction and relaxation compared to the other groups. At 3 Hz cardiomyocytes from MS showed reduction in cell shortening and speed of contraction compared to CS. Protein restriction does not prevent the improvement in physical performance or cardiomyocytes biomechanical efficiency and growth in response to exercise. These findings could represent a modulatory effect of exercise to maintain cardiomyocyte growth at the expense of reducing the rate of body growth in order to ensure proper cellular function in conditions of cardiovascular overload imposed by exercise. PMID:23670356

Cabral, C A C; Natali, A J; Novaes, R D; Lavorato, V N; Drumond, L R; Carneiro Júnior, M A; Silva, M F; Quintão-Junior, J F; Gontijo, L N; Silva, C H O; Felix, L B; Silva, M E



Role of the renin-angiotensin-aldosterone system in the enhancement of salt sensitivity caused by prenatal protein restriction in stroke-prone spontaneously hypertensive rats.  


We previously demonstrated that maternal protein restriction during pregnancy enhanced salt sensitivity and shortened life span in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was conducted to investigate the participation of the renin-angiotensin-aldosterone system in the development of salt sensitivity in the offspring of dams fed a low-protein diet during pregnancy. We used SHRSP offspring from dams fed a 20% casein diet (CN) or a 9% casein diet (LP) during pregnancy. The CN and LP SHRSP offspring were further subdivided into tap-water-drinking and 1%-saline-drinking groups from the postnatal 10th week. A remarkable elevation in blood pressure in response to salt loading was observed in the LP SHRSP offspring. The protein levels of CYP11B2, an enzyme for aldosterone synthesis, were markedly elevated in response to salt loading in the kidneys of LP offspring. Treatment of the LP offspring with an aldosterone receptor antagonist prevented the blood pressure from elevating and lengthened the average life span in LP offspring in response to the drinking of 1% saline. No difference in the activity of angiotensin-converting enzyme or in the protein level of the angiotensin type 1 receptor was found between the CN and LP offspring in either the tap-water-drinking or saline-drinking conditions. In conclusion, the increment of aldosterone production in response to high-salt loading may contribute to the elevated salt sensitivity of the offspring of protein-restricted dams. PMID:21937213

Otani, Lila; Sugimoto, Naoya; Kaji, Misa; Murai, Mariko; Chang, Sue-Joan; Kato, Hisanori; Murakami, Tetsuo



Biochemical and Molecular Roles of Nutrients Protein Restriction Specifically Decreases the Abundance of Serum Albumin and Transthyretin Nuclear Transcripts in Rat Liver1»2  

Microsoft Academic Search

The expression of the genes for serum albumin and several other plasma proteins is decreased in animals consuming inadequate amounts of dietary protein. To define the specificity of this phenomenon, we examined the effect of dietary protein restriction on the abundance of the mRNA for nine genes in rat liver. The results of this and previous studies indicate that genes



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


Impaired pancreatic ?-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

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



Dietary Protein Restriction during F0 Pregnancy in Rats Induces Transgenerational Changes in the Hepatic Transcriptome in Female Offspring  

PubMed Central

There is considerable evidence for non-genomic transmission between generations of phenotypes induced by environmental exposures during development, although the mechanism is poorly understood. We investigated whether alterations in expression of the liver transcriptome induced in F1 offspring by feeding F0 dams a protein-restricted (PR) diet during pregnancy were passed with or without further change to two subsequent generations. The number of genes that differed between adult female offspring of F0 protein-restricted (PR) and protein-sufficient (PS) dams was F1 1,684 genes, F2 1,680 and F3 2,062. 63/113 genes that were altered in all three generations showed directionally opposite differences between generations. There was a trend toward increased proportions of up-regulated genes in F3 compared to F1. KEGG analysis showed that only the Adherens Junctions pathway was altered in all three generations. PR offspring showed altered fasting glucose homeostasis and changes in phosphoenolpyruvate carboxykinase promoter methylation and expression in all three generations. These findings show that dietary challenge during F0 pregnancy induced altered gene expression in all three generations, but relatively few genes showed transmission of altered expression between generations. For the majority of altered genes, these changes were not found in all generations, including some genes that were changed in F3 but not F1, or the direction and magnitude of difference between PR and PS differed between generations. Such variation may reflect differences between generations in the signals received by the fetus from the mother as a consequence of changes in the interaction between her phenotype and the environment.

Hoile, Samuel P.; Lillycrop, Karen A.; Thomas, Nicola A.; Hanson, Mark A.; Burdge, Graham C.



Protein Restriction Without Strong Caloric Restriction Decreases Mitochondrial Oxygen Radical Production and Oxidative DNA Damage in Rat Liver  

Microsoft Academic Search

Previous studies have shown that caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat organs, which can be linked to the slowing of aging rate induced by this regime. These two characteristics are also typical of long-lived animals. However, it has never been investigated if those decreases are linked to the decrease in the intake of

Alberto Sanz; Pilar Caro; Gustavo Barja



Tumoricidal Activity of Lymphokine-Activated Killer Cells During Acute Protein Restriction in the Cotton Rat ( Sigmodon hispidus)  

Microsoft Academic Search

Habitat-induced alterations of immune system function have been implicated in the regulation of survival rates in wild herbivore populations. Protein availability in the diet has been shown to fluctuate with density and influence immunity in hispid cotton rats (Sigmodon hispidus), a common herbivorous rodent of the southeastern United States. In this study, we examined the impact of short-term, moderate restrictions

R. L Lochmiller; J. A Sinclair; D. P Rafferty



Tumoricidal activity of lymphokine-activated killer cells during acute protein restriction in the cotton rat (Sigmodon hispidus).  


Habitat-induced alterations of immune system function have been implicated in the regulation of survival rates in wild herbivore populations. Protein availability in the diet has been shown to fluctuate with density and influence immunity in hispid cotton rats (Sigmodon hispidus), a common herbivorous rodent of the southeastern United States. In this study, we examined the impact of short-term, moderate restrictions in dietary protein on the tumoricidal activity of lymphokine-activated killer (LAK) cells in the spleen of subadult male cotton rats in captivity. Animals were fed complete, isocaloric diets containing either 20% casein (high quality diet), or one of three moderate levels of protein (10, 8, or 5% casein) for two weeks prior to assessing LAK cell activity in vitro in the presence of YAC-1 tumor cells. Moderate restrictions in protein resulted in depressed body growth, although all animals gained mass during the second week of the trial, without significant increases in food intake. Immune organ development and cellularity were suppressed in moderately restricted cotton rats when compared to those on a high quality diet. Tumoricidal activity of LAK cells against YAC-1 targets were significantly altered by diet treatments, being elevated in the group fed a diet containing 10% casein. There was a general tendency for increased LAK cell activity among those fed one of the three moderate quality diets, but observed suppressions in splenic cellularity tended to result in a slight decline in total lytic capacity of spleens. PMID:9669084

Lochmiller, R L; Sinclair, J A; Rafferty, D P



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


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

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



Prolactin Stimulation of Maternal Behavior in Female Rats  

Microsoft Academic Search

Inexperienced, hypophysectomized female rats treated with steroids were used in experiments to investigate the roles of the pituitary gland and prolactin in the expression of maternal behavior. Administration of ovine prolactin or treatment with ectopic pituitary grafts, which release prolactin into the circulation, stimulated maternal care in these females toward rat young. Steroid treatment alone, while stimulating maternal behavior in

Robert S. Bridges; Rosemarie Dibiase; Donna D. Loundes; Paul C. Doherty



Effect of maternal low protein diet during pregnancy on the fetal liver of rats.  


Maternal protein restriction plays a critical role in the developmental programming of later disease susceptibility of the fetus. Developmental insults could exert permanent effects on health through alteration of tissue morphology. As the liver has the greatest number of functions among other body organs, this study aimed at evaluating the effects of maternal dietary protein insufficiency on the structure and the proliferative capacity of the liver in rat fetuses. Morphometric histological studies and biochemical analysis were performed. Twenty adult Albino female Wistar rats were divided into two groups after confirmation of pregnancy. Group I (ST), serving as control, was fed a standard diet (20% protein) and group II (LP) a low protein diet (5% protein). Fetuses were extracted on the day 21.5 of pregnancy. Group II morphometric results revealed a significant decrease in the mothers' weight gain, number and weight of fetuses and weight of fetal livers, but there was also an increase in the mean area of hepatocytes. Histological results showed apoptosis, vacuolization of the hepatocytes, increased positivity of the Oil Red O stained fat droplets and the PAS-positive stained glycogen granules. Liver TUNEL showed increased apoptotic nuclei. Ki-67 immunostaining showed decreased proliferation of the hepatocytes. Ultrastructurally, the nucleus showed peripheral masses of heterochromatin besides irregular nuclear and cell membranes. Mitochondria varied in shape with loss of cristea. Biochemically, there was a significant decrease in the protein concentration and a significant increase in the glycogen concentration in livers of group II. It thus appears that the maternal metabolic condition not only reduced fetal growth in response to protein restriction, but also altered the structure of the liver. PMID:22877887

Ramadan, Wafaa S; Alshiraihi, Ilham; Al-karim, Saleh



Maternal behavior in the virgin and lactating rat  

Microsoft Academic Search

Observed the onset of maternal behavior in 20 Sprague-Dawley virgin female rats during pup induction, and later compared their behavior with that of 8 lactating mothers. During induction, the onset was sudden rather than gradual, and during maternal care their behavior was similar in almost all respects to that of lactating mothers. Reinduction of maternal behavior in virgins occurred with

Alison S. Fleming; Jay S. Rosenblatt



Dopamine antagonists during parturition disrupt maternal care and the retention of maternal behavior in rats  

Microsoft Academic Search

Brief contact with pups at parturition enables the female rat to establish and retain the full repertoire of maternal behaviors, allowing her to respond rapidly to pups in the future. To determine whether the dopamine system is involved in the retention of maternal behavior, females were continuously infused with dopamine antagonists during the periparturitional period and then allowed either a

Elizabeth M. Byrnes; Beth A. Rigero; Robert S. Bridges



Gestational protein restriction affects trophoblast differentiation  

PubMed Central

Whether and how gestational protein restriction (PR) affects placental development and function remain unknown. To test the hypothesis that PR can affect trophoblast differentiation in mid-and late pregnancy, rats were fed a 20% or an isocaloric 6% protein diet from Day 1 to 14 or 18 of pregnancy and effects of PR on trophoblast differentiation were determined by changes in expressions of marker gene(s) for trophoblast lineages. At Day 18 of pregnancy, PR increased expressions of Esrrb, Id1 and Id2 (trophoblast stem cell markers), decreased expressions of Ascl2 (spongiotrophblast cell marker) and Prl2c1 (trophoblast giant cell marker), but did not alter expressions of Gjb3 and Pcdh12 (glycogen cell markers) in the junctional zone (JZ). In the labyrinth zone (LZ), PR did not change expressions of Prl2b1 (trophoblast giant cell marker), Gcm1 and Syna (syncytiotrophoblast cell markers), but decrease expression of Ctsq (sinusoidal trophoblast giant cell marker). These results indicate that PR impairs the differentiation of trophoblast stem cell into spongiotrophoblast and trophoblast giant cells in JZ, and formation of sinusoidal trophoblast giant cells in LZ.

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra



Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats  

PubMed Central

Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP)-A gene expression in human lung epithelial cell lines (H441). The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5?mg/kg/day) on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5?mg/kg/day) on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

Chen, Chung-Ming; Wang, Leng-Fang; Cheng, Kur-Ta



Effects of maternal protein malnutrition on oxidative markers in the young rat cortex and cerebellum.  


Malnutrition affects a large number of children worldwide. Inadequate nutrition during pre- and postnatal period may alter brain development resulting in biochemical, physiological and anatomical changes which in turn could cause behavioral abnormalities. The impairment of the central nervous system following protein deficit have been extensively studied and this deprivation produces deleterious effects upon cerebral structures. The aim of this study was to identify oxidative parameters present in the developing brain as consequence of maternal protein malnutrition. Female Wistar rats were fed a normal protein diet (25% casein) or low protein diet (8% casein) from the time of conception up to 21 days after the parturition. In addition, the diets were supplemented or not with l-methionine. Cortex and cerebellum were removed from offspring to determine the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and the levels of lipoperoxidation (TBARS). Our findings demonstrated heterogeneity in response to protein restriction. The levels of lipoperoxidation were increased in the cerebellum of malnourished offspring. Methionine supplementation caused an increase in lipoperoxidation in both brain structures. CAT activity was decreased in the cerebellum of the offspring supplemented with methionine whereas the cerebellum of malnourished pups with or not methionine supplementation showed a decrease in SOD activity. The activity of SOD in the cortex did not differ among groups. CAT activity, however, was increased in the cortex of malnourished pups supplemented or not with methionine. Thus, these results provide clues to the knowledge of malnutrition effects upon the brain. PMID:16930840

Bonatto, Fernanda; Polydoro, Manuela; Andrades, Michael Everton; Conte da Frota, Mário Luiz; Dal-Pizzol, Felipe; Rotta, Liane Nanci; Souza, Diogo Onofre; Perry, Marcos Luiz; Fonseca Moreira, José Cláudio



Interaction of maternal separation on the UCh rat cerebellum.  


Maternal care is the main source of signals and stimuli for proper development, growth, and production of adjustment responses to stressful factors. Adverse experiences in childhood are associated with a vulnerability to developing abusive ethanol ingestion via alterations of the response of the hypothalamic-pituitary-adrenal axis. Alcoholism causes global brain abnormalities, with the cerebellum being one of the most susceptible areas. We evaluated the effect of maternal separation on the cerebellum structure of male UCh rats. Adult male UChA (low 10% ethanol consumption) and UChB (high 10% ethanol consumption) rats were divided in to four experimental groups: (1) UChA, (2) UChA maternal separation (MS), (3) UChB, and (4) UChB MS. The MS occurred between the 4th and 14th days of age, for 240 min day(-1) . Euthanasia was performed at 120 days of age. An image analysis system was used to measure cerebellar cortical height and Purkinje cellular area and height in five rats from each group. The cerebellar sections were stained with antibodies against IGFR-I. MS did not alter the ethanol consumption of UChA and UChB rats. Corticosterone level was significantly higher in UChA MS and UChB MS rats than in UChA and UChB rats. The Purkinje cellular area and height were higher in UChA MS rats. IGFR-I expression was observed in the cortical glomerular area of UChA MS and UChB MS rats. MS altered the Purkinje cells in the cerebella of male UCh rats. PMID:24203397

Oliveira, S A; Fontanelli, B A F; Stefanini, M A; Chuffa, L G A; Teixeira, G R; Lizarte, F S N; Tirapelli, L F; Quitete, V H A; Matheus, S M M; Padovani, C R; Martinez, M; Martinez, F E



Altered placental development in undernourished rats: role of maternal glucocorticoids  

PubMed Central

Maternal undernutrition (MUN) during pregnancy may lead to fetal intrauterine growth restriction (IUGR), which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs) has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1), 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1) predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC) to corticosterone, although can sometimes drive the opposing (inactivating reaction), and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents) in control and MUN rats at embryonic day 20 (E20). Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3) and amino acids (SLC38A1, 2, and 4). Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC38A1, and SLC38A2 expression, and by increased SLC38A4 expression, in labyrinth zones from the mid- and proximal-horns. In marked contrast to the labyrinth zone, the basal zone, which is the site of hormone production, did not show significant changes in any of these enzymes or transporters. These results suggest that dysregulation of the labyrinth zone GC "barrier", and more importantly decreased nutrient supply resulting from downregulation of some of the amino acid system A transporters, may contribute to suboptimal fetal growth under MUN.



Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on ?-cell function and insulin sensitivity.  


Dietary protein restriction during pregnancy and lactation in rats impairs ?-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores ?-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of ?-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation on ?-cell function and insulin resistance in these offspring. Pregnant rats were fed i) control, ii) LP, and iii) LP+Tau diets during gestation and lactation. Offspring were given a control diet following weaning. A fourth group consisting of offspring of LP-fed mothers, maintained on a LP diet following weaning, was also studied (LP-all life). Insulin sensitivity in the offspring of LP-fed mothers was reduced in females but not in males. In both genders, LP exposure decreased ?-cell function. Tau supplementation improved insulin sensitivity in females and ?-cell function in males. The LP-all life diet improved ?-cell function in males. We conclude that i) maternal Tau supplementation has persistent effects on improving glucose metabolism (?-cell function and insulin sensitivity) in adult rat offspring of LP-fed mothers and ii) increasing the amount of protein in the diet of offspring adapted to a LP diet after weaning may impair glucose metabolism (?-cell function) in a gender-specific manner. PMID:23613616

Tang, Christine; Marchand, Kelly; Lam, Loretta; Lux-Lantos, Victoria; Thyssen, Sandra M; Guo, June; Giacca, Adria; Arany, Edith



Folic acid and protein content in maternal diet and postnatal high-fat feeding affect the tissue levels of iron, zinc, and copper in the rat.  


Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n?=?48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p?maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p?maternal dietary folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation. PMID:21484405

Król, Ewelina; Krejpcio, Zbigniew; Chmurzynska, Agata



Differential involvement of nucleus accumbens shell and core subregions in maternal memory in postpartum female rats.  


Maternal memory refers to the long-term retention of maternal responsiveness as a consequence of animals' prior experiences with their young. This study examined the relative roles of 2 subregions of the nucleus accumbens (NA; shell and core) in maternal memory in rats. NA shell lesions either before or immediately after a short experience significantly disrupted maternal memory, but lesions after a 24-hr maternal experience had no effect. NA core lesions had no significant impact on maternal memory. Cycloheximide (a protein synthesis inhibitor) at a high dose (25 micrograms/microliter) infused in the NA shell immediately after 1 hr of maternal experience also significantly disrupted maternal memory, whereas infusions in the medial preoptic area had no effect. It was concluded that the NA shell, but not the NA core, is involved in the consolidation of maternal memory. PMID:12802872

Li, Ming; Fleming, Alison S



Involvement of Renal Corpuscle microRNA Expression on Epithelial-to-Mesenchymal Transition in Maternal Low Protein Diet in Adult Programmed Rats  

PubMed Central

Prior study shows that maternal protein-restricted (LP) 16-wk-old offspring have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate, besides enhanced glomerular area, which may be related to glomerular hyperfiltration/overflow and which accounts for the glomerular filtration barrier breakdown and early glomerulosclerosis. In the current study, LP rats showed heavy proteinuria associated with podocyte simplification and foot process effacement. TGF-?1 glomerular expression was significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR-200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1?1/2 mRNA expression. By western blot analyzes of whole kidney tissue, we found significant reduction of both podocin and nephrin and enhanced expression of mesenchymal protein markers such as desmin, collagen type I and fibronectin. From our present knowledge, these are the first data showing renal miRNA modulation in the protein restriction model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced stage of fibrosis, which led us to state that the glomerular miR-200 family would be downregulated by TGF-?1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition.

Sene, Leticia de Barros; Mesquita, Flavia Fernandes; de Moraes, Leonardo Nazario; Santos, Daniela Carvalho; Carvalho, Robson; Gontijo, Jose Antonio Rocha; Boer, Patricia Aline



Effects of protein restriction during gestation and lactation on cell proliferation in the hippocampus and subventricular zone: functional implications. Protein restriction alters hippocampal/SVZ cell proliferation.  


There is no consensus about the effects of protein restriction on neurogenesis and behavior. Here, for the first time, we evaluated the effects of protein restriction during gestation and lactation, on the two major neurogenic regions of the adult brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ), simultaneously. We also assessed different types of behavior relevant to each region. After mating, pregnant Wistar rats were divided into a control group (CG) that received a normal diet (20% protein); and a protein-restriction group (PRG) that received a low-protein diet (8% protein). After birth, the same diets were provided to the mother and pups until weaning, when some rats were analyzed and others received a normal-protein diet until adulthood. Different sets of rats were used for cellular and behavioral studies in juvenile or adult age. Brains were processed for immunohistochemistry anti-BrdU, anti-Ki67, or anti-pHisH3. Juvenile and adult rats from distinct litters also underwent several behavioral tests. Our data show that early protein restriction results in a reduction of hippocampal progenitors and deficits in object recognition during adult life. Moreover, longer periods of immobility in the tail suspension and in the forced swimming tests revealed that PRG rats show a depressive behavior at 21 days of age (P21) and in adulthood. Furthermore, we suggest that despite the reduced number/proliferation of neural stem cells (B and/or E cells) in SVZ there is a compensatory mechanism in which the progenitors (types C and A cells) proliferate in a higher rate, without affecting olfactory ability in adulthood. PMID:23123702

Godoy, Mariana Araya de; Souza, Amanda Santos de; Lobo, Mônica Alves; Sampaio, Omar Vidal Kress; Moraes, Louise; Baldanza, Marcelo Ribeiro; Magri, Tatiana Przybylski Ribeiro; Wernerck de Castro, João Pedro Saar; Tavares do Carmo, Maria das Graças; Soares-Mota, Márcia; Rocha, Monica Santos; Mendez-Otero, Rosalia; Santiago, Marcelo Felippe



Maternal Separation Uncouples Reflex From Spontaneous Voiding in Rat Pups  

PubMed Central

Purpose Rat pups only void when the perigenital-bladder reflex is activated by the mother rat licking the perineum. Maternal separation causes bladder distention as well as stress responses and anxiety behaviors in adult rats. We determined if MS would change voiding reflex maturation in neonatal rats. Materials and Methods A total of 14 Sprague-Dawley rat pups were subjected to 6 hours of daily MS and 17 were subjected to 6 hours of MS with bladder emptying by perigenital stimulation at 3 hours on postnatal days 2 to 14. Age matched controls for the 2 groups remained with the mother. Spontaneous voiding in awake pups from 1 to 3 weeks was monitored in a metabolic cage and perigenital-bladder reflex latency was determined from 1 to 7 weeks. Cystometry was performed at 9 weeks with the rats under urethane anesthesia. Results Spontaneous voiding began at 3 weeks in all animals. The latency of the perigenital-bladder reflex at 3 weeks was shorter than the latency at 2 days in MS animals (3.3 vs 6.4 seconds, p < 0.01) but not in control or MSPG animals. MS animals maintained the perigenital-bladder reflex 2 weeks longer than control animals. The spontaneous voiding behavior of MSPG animals was similar to that in controls. Conclusions Intermittent bladder distention delays withdrawal of the spinal perigenital-bladder reflex but it does not affect maturation of the supraspinal bladder-bladder reflex that controls spontaneous voiding in older rats. This suggests that increased bladder afferent firing can selectively modulate spinal but not supraspinal mechanisms controlling postnatal changes in voiding function.

Wu, Hsi-Yang; de Groat, William C.



Protein restriction and AST120 improve lipoprotein lipase and VLDL receptor in focal glomerulosclerosis  

Microsoft Academic Search

Protein restriction and AST-120 improve lipoprotein lipase and VLDL receptor in focal glomerulosclerosis.BackgroundImai rats exhibit spontaneous focal glomerulosclerosis (FGS) with progressive proteinuria and hyperlipidemia leading to renal insufficiency by age 34 weeks. Recently, we reported marked down-regulations of skeletal muscle and adipose tissue lipoprotein lipase (LPL) and very low-density lipoprotein (VLDL) receptor in male Imai rats at 32 weeks of

Tadashi Sato; Kaihui Liang; Nosratola D. Vaziri



Sedation and disruption of maternal motivation underlie the disruptive effects of antipsychotic treatment on rat maternal behavior  

PubMed Central

The behavioral mechanisms underlying antipsychotic-induced maternal behavior deficits were examined in the present study. Different groups of postpartum rats were treated with haloperidol (0.1 mg/kg), clozapine (10.0 mg/kg), chlordiazepoxide (5.0 mg/kg, an anxiolytic) or vehicle (0.9% saline) on Days 4 and 6 postpartum and their maternal behaviors were tested under either pup-separation (e.g. pups were removed from their mothers for 4 h before testing) or no-pup-separation condition. Maternal behavior and drug-induced sedation were further tested for 3 days from Day 8 to 12 postpartum. Results show that pup-separation, which putatively increases maternal motivation, did significantly shorten clozapine-elongated pup approach latency, increase pup licking and nursing but fail to reverse the deficits in pup retrieval and nest building in the lactating rats treated with haloperidol and clozapine. Repeated haloperidol treatment produced a progressively enhanced disruption on pup retrieval and nest building and an attenuated sedation. In contrast, clozapine showed a progressively diminished disruption on pup retrieval and a concomitantly diminished sedative effect. Based on these findings, we suggest that antipsychotic drugs disrupt active maternal responses at least in part by suppressing maternal motivation, and drug-induced sedation also contributes to this disruptive effect, especially with clozapine.

Zhao, Changjiu; Li, Ming



IFITM Proteins Restrict Viral Membrane Hemifusion  

PubMed Central

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.

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



Growth and Development of Rats in Relation to the Maternal Diet: A Review.  

National Technical Information Service (NTIS)

Ad libitum fed progeny of mother rats fed a restricted diet during gestation and lactation show permanent growth stunting, feed and nitrogen wastage and carbohydrate intolerance; neuromotor development is delayed and abnormal. When the maternal dietary re...

B. F. Chow R. Sherwin A. M. Hsueh B. N. Blackwell R. Q. Blackwell



Effects of early maternal separation on subsequent reproductive and behavioral outcomes in male rats.  


ABSTRACT To investigate effects of maternal separation on reproductive and behavioral outcomes, male Wistar rats were separated from their mothers daily for 3 hr (maternal separation; MS) or 0 hr (control) from postnatal day (PND) 1 to 14. Timing of puberty, reproductive parameters, hormone levels, and aggressive behaviors in juvenile and adult rats were examined. Contrary to expectations, there was no effect of maternal separation on any measure of aggression. However, maternal separation altered peripubertal testosterone secretion and increased mean day of preputial separation. In addition, adult MS males demonstrated less total sexual behavior. There was no difference in sperm counts or testosterone levels at necropsy on PND 56 or in adulthood, but seminal vesicle weights were increased in adult MS rats. These results suggest that early life stress may influence hypothalamic-pituitary-gonadal axis development in males, at least during peripuberty. PMID:24940813

Bodensteiner, Karin J; Christianson, Nina; Siltumens, Aldis; Krzykowski, Julie



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


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=23.3±0.5 v. CM=18.2±0.7, 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=4.1±0.7, n=8 v. CM=7.0±0.5, 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

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



The effects of maternal caffeine intake during pregnancy on mineral contents of fetal rat bone  

Microsoft Academic Search

Summary Various levels of maternal caffeine ingestion during pregnancy were investigated to determine whether caffeine will affect the mineral contents of the growing bones of fetal rats. On day 8 of gestation, rat dams were fed with a 20% protein diet supplemented with 0.5 mg, 1 mg, or 2 mg caffeine\\/100 g of dams body weight as an experimental group

T. Nakamoto; S. Grant; M. Yazdani



Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia  

Microsoft Academic Search

Objective: To determine whether severe maternal hypoxia affects fetal rat physical characteristics and causes neuronal damage, and whether magnesium sulfate can decrease these effects.Methods: At 17 days gestation, rats were randomly assigned to one of four groups that received saline injections and room air (n = 6), magnesium sulfate and room air (n = 5), saline and hypoxia (n =

Mordechai Hallak; John W Hotra; William J Kupsky



Maternal Programming of Reproductive Function and Behavior in the Female Rat  

PubMed Central

Parental investment can be used as a forecast for the environmental conditions in which offspring will develop to adulthood. In the rat, maternal behavior is transmitted to the next generation through epigenetic modifications such as methylation and histone acetylation, resulting in variations in estrogen receptor alpha expression. Natural variations in maternal care also influence the sexual strategy adult females will adopt later in life. Lower levels of maternal care are associated with early onset of puberty as well as increased motivation to mate and greater receptivity toward males during mating. Lower levels of maternal care are also correlated with greater activity of the hypothalamus–pituitary–gonadal axis, responsible for the expression of these behaviors. Contrary to the transition of maternal care, sexual behavior cannot simply be explained by maternal attention, since adoption studies changed the sexual phenotypes of offspring born to low caring mothers but not those from high caring dams. Indeed, mothers showing higher levels of licking/grooming have embryos that are exposed to high testosterone levels during development, and adoption studies suggest that this androgen exposure may protect their offspring from lower levels of maternal care. We propose that in the rat, maternal care and the in utero environment interact to influence the reproductive strategy female offspring display in adulthood and that this favors the species by allowing it to thrive under different environmental conditions.

Cameron, Nicole M.



Maternal responsiveness to infant Norway rat ( Rattus norvegicus) ultrasonic vocalizations during the maternal behavior cycle and after steroid and experiential induction regimens  

Microsoft Academic Search

When removed from the nest and placed in a cool environment, Norway rat (Rattus norvegicus) pups emit ultrasonic vocalizations that can elicit maternal search behavior. The authors examined the behavior of pregnant dams, mothers, and virgin females during exposure to a pup that was either warm and silent or cool and vocalizing. Results indicate potentiated maternal reactions to a vocalizing

William J. Farrell; Jeffrey R. Alberts



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

Microsoft Academic Search

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

Marcelo T Marin; Cleopatra S Planeta



Prenatal stress eliminates differential maternal attention to male offspring in Norway rats.  


Maternal licking behavior was observed in 20 Long-Evans rat dams on two consecutive days. Stimulus pups were male and female foster pups from dams that were either housed with 5 adult males during the last trimester of pregnancy (stressed) or housed alone (unstressed). Unstressed male pups received significantly more maternal licking than their female siblings, but prenatally stressed males and females received similar levels of maternal licking, comparable to that directed to unstressed females. In a second study, urine collected from prenatally stressed male pups elicited significantly less investigation from dams in a choice test than urine from age-matched unstressed males. It is concluded that the chemosignals which stimulate dams normally to provide more maternal attention to male than female neonates are deficient in prenatally stressed males. The results raise the possibility that differential maternal care may mediate some effects of prenatal stress on behavioral development in males. PMID:3823181

Power, K L; Moore, C L




Microsoft Academic Search

This study describes the maternal-fetal disposition of bisphenol A and its distribution into the placenta and amniotic fluid after iv injection (2 mg\\/kg) to pregnant Sprague-Dawley rats. Bisphenol A was distributed extensively to the placenta and fetus, with their respective AUC values 4.4- and 2.2-fold greater than AUC for the maternal serum. In contrast, the distribution of bisphenol A into

Beom Soo Shin; Sun Dong Yoo; Chang Youn Cho; Ji Hoon Jung; Byung Mu Lee; Jung Ha Kim; Kang Choon Lee; Soon-Young Han; Hyung Sik Kim; Kui Lea Park



Possible Role for Endogenous Oxytocin in Estrogen-Facilitated Maternal Behavior in Rats  

Microsoft Academic Search

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

Susan E. Fahrbach; Joan I. Morrell; Donald W. Pfaff



Maternal deprivation induces depressive-like behaviour and alters neurotrophin levels in the rat brain.  


The present study was aimed to evaluate the behavioral and molecular effects of maternal deprivation in adult rats. To this aim, male rats deprived and non-deprived were assessed in the forced swimming and open-field tests in adult phase. In addition adrenocorticotrophin hormone (ACTH) levels was assessed in serum and brain-derived-neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) protein levels were assessed in prefrontal cortex, hippocampus and amygdala. We observed that maternal deprivation increased immobility time, and decreased climbing time, without affecting locomotor activity. ACTH circulating levels were increased in maternal deprived rats. Additionally, BDNF protein levels were reduced in the amygdala and NT-3 and NGF were reduced in both hippocampus and amygdala in maternal deprived rats, compared to control group. In conclusion, our results support the idea that behavioral, ACTH circulating levels and neurotrophins levels altered in maternal deprivation model could contribute to stress-related diseases, such as depression. PMID:21161589

Réus, Gislaine Z; Stringari, Roberto B; Ribeiro, Karine F; Cipriano, Andreza L; Panizzutti, Bruna S; Stertz, Laura; Lersch, Camila; Kapczinski, Flávio; Quevedo, João



Isoxsuprine infusion in the rat: alterations in maternal, fetal and neonatal glucose homeostasis.  


To determine the mechanism of alteration in glucose homeostasis associated with maternal isoxsuprine administration, isoxsuprine or 0.04 M saline was administered intravenously for 3 hours to term pregnant and age-matched virgin rats. Isoxsuprine infusion significantly increased plasma glucose and insulin concentrations and decreased hepatic glycogen stores in both. Compared to rat pups of saline infused mothers, pups of isoxsuprine infused mothers had significantly elevated plasma glucose concentrations for the first 4 hours of life and plasma insulin concentrations for the first two. Plasma glucose concentrations for the offspring of isoxsuprine treated mothers then decreased significantly and remained so until 16 hours of age. Hepatic glycogen concentrations were significantly less in rat pups of isoxsuprine treated mothers at birth and for the first 4 hours of life. In a limited number of studies, isoxsuprine was present at birth in substantial quantities (80-85% of maternal levels) in the plasma of rat pups of isoxsuprine infused mothers. These data suggest that maternal isoxsuprine therapy mobilizes hepatic glycogen and results in maternal hyperlgycemia. Maternal isoxsuprine infusion may directly deplete fetal hepatic glycogen and result in transient fetal and neonatal hyperglycemia. the in utero depletion of glycogen and possibly, the early stimulation of insulin production may be responsible for the later significant decreases in plasma glucose in the offspring of isoxsuprine treated mothers. PMID:7035644

Ogata, E S



Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats  

Microsoft Academic Search

Chlorpyrifos (CPF), an organophosphorus (OP) insecticide, exerts toxicity through inhibition of acetylcholinesterase (AChE). In the present study, pregnant Sprague?Dawley rats were given CPF (200 mg\\/kg, sc) as a single dose on gestation d 12 (GD12) and then sacrificed on either GD16, GD20, or postnatal d 3 (PND3) for measurement of maternal and developmental indicators of toxicity. While most CPF?treated rats

S. M. Chanda; P. Harp; J. Liu; C. N. Pope



Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats  

Microsoft Academic Search

Acute exposure to the organophosphate pesticide chlorpyrifos (CPF) on gestation day 12 (GD12, 200 mg\\/kg\\/ml, SC) causes extensive neurochemical changes in maternal brain but lesser changes in fetal brain. In the present study, we examined the relative neurotoxicity of repeated, lower-level CPF exposures during gestation in rats. Pregnant Sprague-Dawley rats were exposed to CPF (6.25, 12.5, or 25 mg\\/kg per

S. M. Chanda; C. N. Pope



Maternal caffeine intake impairs MK-801-induced hyperlocomotion in young rats  

Microsoft Academic Search

Here we have investigated the effects of maternal caffeine intake (1 g\\/l) on MK-801-induced hyperlocomotion in rat pups. Animals submitted to caffeine treatment during the gestational and lactational period were separated in two groups: caffeine-treated group (up to 21 days old) and washout group (caffeine treatment up to 7 days old). MK-801 (0.25 mg\\/kg, i.p.) promoted hyperlocomotion in control rats,

Rosane Souza da Silva; Anselmo Hoffman; Diogo Onofre de Souza; Diogo R. Lara; Carla Denise Bonan



Toxic effects of maternal zearalenone exposure on uterine capacity and fetal development in gestation rats.  


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

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



Stimulus control of maternal responsiveness to Norway rat ( Rattus norvegicus) pup ultrasonic vocalizations  

Microsoft Academic Search

Mother rats (Rattus norvegicus; 6 to 8 days postpartum) approach and maintain proximal orientation to a pup that is emitting ultrasonic vocalizations (USVs) far more than do virgin females (W. J. Farrell & J. R. Alberts, 2002). We used a playback regimen to examine the roles of acoustic and nonacoustic cues in regulating maternal proximal orientation toward vocalizing pups. When

William J. Farrell; Jeffrey R. Alberts



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...



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...


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

Microsoft Academic Search

In a previous study, we showed that exposure of rats to dexamethasone (Dex) selectively in late pregnancy produces permanent induction of hepatic phospho- enolpyruvate 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

M J Nyirenda; LAM Welberg; J R Seckl




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...



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...


Maternal separation enhances neuronal activation and cardiovascular responses to acute stress in borderline hypertensive rats  

Microsoft Academic Search

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

Brian J. Sanders; Alan Anticevic



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

PubMed Central

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 rats—NMS: 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.

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



Effects of chemically induced maternal toxicity on prenatal development in the rat.  


The hypothesis that chemically induced overt maternal toxicity induces a characteristic syndrome of adverse developmental effects in the rat was investigated. Pregnant animals (Sprague-Dawley strain) were dosed by oral gavage with one of a series of compounds on days 6-15 of gestation. These chemicals were diquat (DIQ), ethylene-bis-isothiocyanate (EBIS), toxaphene (TOX), styrene (STY), 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenol (2,4,5-Tr), triphenyl tin hydroxide (TPTH), and cacodylic acid (CAC). The compounds were chosen because they exhibited little or no developmental toxicity in previous studies. Dosage levels producing maternal weight loss and/or lethality were determined from preliminary toxicity studies. Significant maternal weight reductions were noted during the course of treatment with all compounds except CAC and 2,4,5-Tr. Maternal lethality was produced by EBIS, TOX, 2,4,-D, and 2,4,5-Tr. The main treatment-related developmental toxicity noted in litters at term consisted of increased lethality (EBIS, TPTH) and decreased fetal weight (EBIS and CAC). Treatment-related anomalies were seen in litters treated with 2,4-D and TOX (supernumerary ribs) and with EBIS and STY (enlarged renal pelvis). No significant developmental effects were produced with DIQ, or 2,4,5-Tr. This study indicates that overt maternal toxicity as defined by weight loss or mortality is not always associated with the same defined syndrome of adverse developmental effects in the rat. PMID:2087686

Chernoff, N; Setzer, R W; Miller, D B; Rosen, M B; Rogers, J M



Maternal nicotine exposure: response of type II pneumocytes of neonatal rat pups.  


The influence of maternal nicotine exposure during pregnancy and lactation on the Type II cells of lung tissue of one day old neonatal rat pups was investigated. The results clearly show that maternal nicotine exposure resulted in an increase in the type II cell count in the lungs of the offspring. In addition the lamellar body content of the type II cells of the nicotine exposed rat pups were significantly (P < 0.01) higher than that of the control animals. The type II cell mitochondria of lung tissue of nicotine exposed rat pups were swollen and no microvilli occurred on the alveolar surface. This clearly illustrates that nicotine interfered with type II cell integrity of tlte neonatal lung and may subsequently interfere with the normal development of the alveolar region of the lung. PMID:7613520

Maritz, G S; Thomas, R A



Maternal Programming of Sexual Behavior and Hypothalamic-Pituitary-Gonadal Function in the Female Rat  

PubMed Central

Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG) over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1) increased sexual receptivity; 2) increased plasma levels of luteinizing hormone (LH) and progesterone at proestrus; 3) an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH) expression in the medial preoptic region; and 4) increased estrogen receptor ? (ER?) expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ER? expression.

Cameron, Nicole; Del Corpo, Adina; Diorio, Josie; McAllister, Kelli; Sharma, Shakti; Meaney, Michael J.



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


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

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



Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring.  


Hypothalamic appetite regulators neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) are modulated by glucose. This study investigated how maternal obesity disturbs glucose regulation of NPY and POMC, and whether this deregulation is linked to abnormal hypothalamic glucose uptake-lactate conversion. As post-natal high-fat diet (HFD) can exaggerate the effects of maternal obesity, its additional impact was also investigated. Female Sprague Dawley rats were fed a HFD (20 kJ/g) to model maternal obesity. At weaning, male pups were fed chow or HFD. At 9 weeks, in vivo hypothalamic NPY and POMC mRNA responses to acute hyperglycemia were measured; while hypothalami were glucose challenged in vitro to assess glucose uptake-lactate release and related gene expression. Maternal obesity dampened in vivo hypothalamic NPY response to acute hyperglycemia, and lowered in vitro hypothalamic glucose uptake and lactate release. When challenged with 20 mM glucose, hypothalamic glucose transporter 1, monocarboxylate transporters, lactate dehydrogenase-b, NPY and POMC mRNA expression were down-regulated in offspring exposed to maternal obesity. Post-natal HFD consumption reduced in vitro lactate release and monocarboxylate transporter 2 mRNA, but increased POMC mRNA levels when challenged with 20 mM glucose. Overall, maternal obesity produced stronger effects than post-natal HFD consumption to impair hypothalamic glucose metabolism. However, they both disturbed NPY response to hyperglycemia, potentially leading to hyperphagia. PMID:24266392

Chen, Hui; Simar, David; Morris, Margaret J



Release of Zn from maternal tissues in pregnant rats deficient in Zn or Zn and Ca  

SciTech Connect

Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of Zn deficiency. The hypothesis that Zn may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague Dawley females were injected with Zn-65; after equilibration, the two major pools of Zn, bone and muscle, had different specific activities (SA), muscle being much higher. Females were mated and fed diets adequate in Zn and Ca (C) or deficient in Zn (ZnD) or deficient in both Zn and Ca (ZnCaD). Calculations using weight loss in ZnD and ZnCaD rats, Zn content of maternal bone and muscle, and total fetal Zn at term indicated that in ZnCaD rats a relatively small amount of Zn from bone early in pregnancy was sufficient to prevent abnormal organogenesis, but most fetal Zn came from breakdown of maternal muscle in the last 3 days of pregnancy. Isotope data supported this conclusion. SA of Zn in ZnD fetuses was equal and high, indicating that most Zn came from the same maternal tissue. High muscle SA prior to mating, and increased SA in tibia and liver during pregnancy suggest that muscle provided Zn for other maternal tissues as well as fetuses. In contrast, SA in C fetuses was less than 30% of that of the D groups, consistent with the earlier hypothesis that most fetal Zn in C rats is accrued directly from the diet.

Hurley, L.S.; Masters, D.G.; Lonnerdal, B.; Keen, C.L.



Sustained hyperphagia in adolescent rats that experienced neonatal maternal separation  

Microsoft Academic Search

Objective:To examine the neurobiological basis of bingeing-related eating disorders using an animal model system.Design:Sprague–Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (maternal separation (MS)), or left undisturbed (non-handled (NH)). Pups were subjected to repeated fasting\\/refeeding (RF) cycles; that is, 24 h food deprivation and 24 h RF (NH\\/RF or MS\\/RF), or

V Ryu; J-H Lee; S B Yoo; X F Gu; Y W Moon; J W Jahng



Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets  

Microsoft Academic Search

Epidemiological evidence that hypertension and coronary heart disease are programmed by exposure to poor diet during intrauterine life, is supported by animal experiments. In the rat, fetal exposure to a maternal low protein diet is associated with abnormal fetal growth and later elevation of blood pressure. Fetal exposure to glucocorticoids of maternal origin are proposed to underlie this association. Pregnant

Simon C Langley-Evans; Margaret Nwagwu



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

PubMed Central

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.

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



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


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/kg·body 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

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



Maternal separation attenuates the effect of adolescent social isolation on HPA axis responsiveness in adult rats.  


Adverse early life experiences that occur during childhood and adolescence can have negative impacts on behavior later in life. The main goal of our work was to assess how the association between stressful experiences during neonatal and adolescent periods may influence stress responsiveness and brain plasticity in adult rats. Stressful experiences included maternal separation and social isolation at weaning. Three hours of separation from the pups (3-14 PND) significantly increased frequencies of maternal arched-back nursing and licking-grooming across the first two weeks postpartum. Separation also induced a long-lasting increase in dams blood levels of corticosterone. Maternal separation did not modify brain and plasma allopregnanolone and corticosterone levels in adult offspring, but they demonstrate partial recovery from the reduction induced by social isolation during adolescence. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were subjected to maternal separation was markedly reduced with respect to that observed in animals that were just socially isolated. All experimental groups showed a significant reduction of BDNF and Arc protein expression in the hippocampus. However, the reduction of BDNF observed in animals that were maternally separated and subjected to social isolation was less significantly pronounced than in animals that were just socially isolated. The results sustained the mismatch hypothesis stating that aversive experiences early in life trigger adaptive processes, thereby rendering an individual to be better adapted to aversive challenges later in life. PMID:24745548

Biggio, F; Pisu, M G; Garau, A; Boero, G; Locci, V; Mostallino, M C; Olla, P; Utzeri, C; Serra, M



Trophoblast invasion and blood vessel remodeling are altered in a rat model of lifelong maternal obesity.  


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

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



Changes in the metabolism of hypothalamic norepinephrine associated with the onset of maternal behavior in the nulliparous rat.  


Both norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were assayed both in the hypothalamus of nulliparous rats that had behaved maternally toward foster young and in the hypothalamus of those that had failed to behave maternally. It was found that the maternally-behaving animals had both lower concentrations of NE and higher concentrations of MHPG as compared with their nonresponding counterparts. These data parallel those reported for the puerperal female and suggest that the onset of maternal behavior may be mediated by increased transmission across hypothalamic noradrenergic synapses. PMID:790399

Rosenberg, P; Leidahl, L; Halaris, A; Moltz, H



Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.  


A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-? and IL-1? cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (p<0.05). Deprived rats treated with saline presented a decrease on BDNF levels in the amygdala (p<0.05), compared with all other groups. The IL-10 levels were decreased in the serum (p<0.05). TNF-? and IL-1? levels were increased in the serum and CSF of deprived rats treated with saline (p<0.05). Interestingly, imipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (p<0.05). Finally, these findings further support a relationship between immune activation, neurotrophins and the depression, and considering the action of imipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system. PMID:23238043

Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João



Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats  

Microsoft Academic Search

Gestational stress (GS) produces profound behavioural impairments in the offspring and may permanently programme hypothalamic–pituitary–adrenal (HPA) axis function. We investigated whether or not GS produced changes in the maternal behaviour of rat dams, and measured depression-like behaviour in the dam, which might contribute to effects in the progeny. We used the Porsolt test, which measures immobility in a forced-swim task,

J. W Smith; J. R Seckl; A. T Evans; B Costall; J. W Smythe



All Trans-Retinoic Acid in Maternal Plasma and Teratogenicity in Rats and Rabbits  

Microsoft Academic Search

The teratogenicity of all-trans-retinoic acid, 13-cis-retinoic acid, and retinol was investigated in pregnant Wistar rats given a single oral dose on Day 10 of gestation. External malformations showed dose-dependent increases and the order of potency was all-trans-retinoic acid > retinol > 13-cis-retinoic acid. The metabolites in maternal plasma were determined following a single oral dose on Day 10 of gestation.

E. A. Tembe; R. Honeywell; N. E. Buss; A. G. Renwick



Changes in bone components of newborn rats after maternal treatment with cytarabine  

Microsoft Academic Search

Concentration of abundant elements like calcium as well as elements present in trace amount like zinc, iron, silicon, potassium in mandibles of 7, 14 an 28 day old newborn rats after maternal administration with cytarabine were determined by X-ray fluorescence analysis. The studies were carried out using measurement system containing X-ray tube ECLIPSE-III and X-ray and gamma ray detector XR-lOOT-CdTe

Zofia Drzazga; Katarzyna Michalik; Michael Kaszuba; Hanna Trzeciak



Ethanol prevents NMDA receptor reduction by maternal separation in neonatal rat hippocampus  

Microsoft Academic Search

We measured the effects of ethanol on glutamate receptor levels in the hippocampus of neonatal Wistar rats using a vapor chamber model. Two control groups were used; a normal suckle group and a maternal separation group. Levels of NMDA receptors were not significantly altered in ethanol-treated animals compared to the normal suckle control group, as shown by [3H]MK-801 binding and

Frederick P. Bellinger; Mark S. Davidson; Kuldip S. Bedi; Peter A. Wilce



Di(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon maternal exposure  

Microsoft Academic Search

Lipids, especially essential fatty acids (EFAs), play critical roles in guiding proper fetal development. Exposure to xenobiotics\\u000a that may alter the fetal supply of EFAs\\/lipids could potentially lead to fetotoxicity. In this study, we investigated the\\u000a effects of the peroxisome proliferator chemical, di-(2-ethylhexyl)-phthalate (DEHP), on the lipid metabolomic profile of the\\u000a rat fetal brain upon maternal exposure during gestation. Female

Yan Xu; Shruti Agrawal; Thomas J. Cook; Gregory T. Knipp



Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny  

Microsoft Academic Search

The long-term consequences of a physiological-range increase of maternal corticosterone during lactation were investigated on the 15-month-old progeny. The offspring of rats drinking water supplemented with corticosterone (200?g\\/ml of corticosterone hemisuccinate) from day 1 postpartum to weaning exhibited: (i) better performance in a conditioned learning test; (ii) reduction of fearfulness in two conflict situations; (iii) lower stress-induced corticosterone secretion and

A Catalani; P Casolini; S Scaccianoce; F. R Patacchioli; P Spinozzi; L Angelucci



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

NASA Astrophysics Data System (ADS)

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.

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



Maternal care associates with play dominance rank among adult female rats.  


Variations in maternal care influence important life history traits that determine reproductive fitness. The adult female offspring of mothers that show reduced levels of pup licking/grooming (LG; i.e., low-LG mothers) show increased defensive responses to stress, accelerated pubertal development, and greater sexual receptivity than the female offspring of high-LG mothers. Amongst several species an accelerated pattern of reproductive development is associated with increased dominance-related behaviors and higher social rank. We hypothesize that rats from low-LG dams may thus also secure higher social rank as a means to compete for limited resources with conspecifics. In this study, social interactions were observed in triads of adult female rats aged p90 that received low, mid, and high levels of pup LG over the first week of life. Low- and mid-LG females had the highest pinning scores and high-LG rats the lowest, showing that low- and mid-LG adult females engage in greater play dominance-related behavior. Likewise, low- and mid-LG rats spent significantly more time drinking following 24?hr of water deprivation in a water competition test thus allowing them to secure a limited resource more easily than high-LG rats. Interestingly, pinning by play dominant females was increased when subordinates were sexually receptive (proestrus/estrus), suggestive of a process of reproductive suppression. Some evidence suggests that low-LG and mid-LG rats also show greater fecundity than high-LG rats. Variations in maternal care may thus have a long-term influence on the development of play dominance and possibly social rank in the female rat, which might contribute to reproductive success within a competitive environment. PMID:22786820

Parent, Carine I; Del Corpo, Adina; Cameron, Nicole M; Meaney, Michael J



Maternal tobacco smoke increased visceral adiposity and serum corticosterone levels in adult male rat offspring.  


Background:Maternal tobacco smoke (MTS) predisposes human and rat offspring to visceral obesity in early adulthood. Glucocorticoid excess also causes visceral obesity. We hypothesized that in utero MTS would increase visceral adiposity and alter the glucocorticoid pathway in young adult rats.Methods:We developed a novel model of in utero MTS exposure in pregnant rats by exposing them to cigarette smoke from E11.5 to term. Neonatal rats were cross-fostered to control dams and weaned to standard rat chow through young adulthood (postnatal day 60).Results:We demonstrated increased visceral adiposity (193%)*, increased visceral adipose 11-? hydroxysteroid dehydrogenase 1 mRNA (204%)*, increased serum corticosterone (147%)*, and no change in glucocorticoid receptor protein in adult male MTS rat offspring. Female rats exposed to MTS in utero demonstrated no change in visceral or subcutaneous adiposity, decreased serum corticosterone (60%)*, and decreased adipose glucocorticoid receptor protein (66%)*. *P < 0.05.Conclusion:We conclude that in utero MTS exposure increased visceral adiposity and altered in the glucocorticoid pathway in a sex-specific manner. We speculate that in utero MTS exposure programs adipose dysfunction in adult male rat offspring via alteration in the glucocorticoid pathway. PMID:24727947

Zinkhan, Erin K; Lang, Brook Y; Yu, Baifeng; Wang, Yan; Jiang, Chengshe; Fitzhugh, Melanie; Dahl, Marjanna; Campbell, Michael S; Fung, Camille; Malleske, Daniel; Albertine, Kurt H; Joss-Moore, Lisa; Lane, Robert H



Neural and Environmental Factors Impacting Maternal Behavior Differences in High- versus Low-Novelty Seeking Rats  

PubMed Central

Selective breeding of rats exhibiting differences in novelty-induced locomotion revealed that this trait predicts several differences in emotional behavior. Bred High Responders (bHRs) show exaggerated novelty-induced locomotion, aggression, and psychostimulant self-administration, compared to bred Low Responders (bLRs), which are inhibited and prone to anxiety- and depression-like behavior. Our breeding studies highlight the heritability of the bHR/bLR phenotypes, although environmental factors like maternal care also shape some aspects of these traits. We previously reported that HR vs. LR mothers act differently, but it was unclear whether their behaviors were genetically driven or influenced by their pups. The present study (a) used cross-fostering to evaluate whether the bHR/bLR maternal styles are inherent to mothers and/or are modulated by pups; and (b) assessed oxytocin and oxytocin receptor mRNA expression to examine possible underpinnings of bHR/bLR maternal differences. While bHR dams exhibited less maternal behavior than bLRs during the dark/active phase, they were very attentive to pups during the light phase, spending greater time passive nursing and in contact with pups compared to bLRs. Cross-fostering only subtly changed bHR and bLR dams’ behavior, suggesting that their distinct maternal styles are largely inherent to the mothers. We also found elevated oxytocin mRNA levels in the supraoptic nucleus of the hypothalamus in bHR versus bLR dams, which may play some role in driving their behavior differences. Overall these studies shed light on the interplay between the genetics of mothers and infants in driving differences in maternal style.

Clinton, Sarah M.; Bedrosian, Tracy A.; Abraham, Antony D.; Watson, Stanley J.; Akil, Huda



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

PubMed Central

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.

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



Effects of maternal ethanol consumption during pregnancy or lactation on intestinal absorption of folic acid in suckling rats  

Microsoft Academic Search

A fostering\\/crossfostering analysis of the effects of maternal ethanol exposure on jejunal and ileal folate absorption was performed. Male and female rats were randomized into two groups. In the first group, ethanol-treated rats received ad libitum 5, 10 and 15% ethanol in the drinking fluid during three successive weeks. A consumption of 20% was maintained in this group for 5

M. L Murillo-Fuentes; M. L Murillo; O Carreras



Behavioral and neurochemical characterization of maternal care effects on juvenile Sprague-Dawley rats.  


Maternal care represents a major constituent of early life environment and has the potential to modulate critical neurobehavioral responses to stress. The aim of the present study was to determine the effects of naturally occurring variations in maternal care on behavioral and neurochemical responses of juvenile Sprague-Dawley rats. A group of dams were classified based on their licking behavior in high and low licking-grooming mothers. Afterwards, the male offspring was tested in a series of behavioral tests: open field test (OFT), elevated plus maze (EPM) and forced swimming test (FST). Additionally, monoamine concentrations were determined post-mortem in three brain regions: hippocampus, ventral striatum and prefrontal cortex. Our findings suggest that maternal care variations have an effect on several anxiety-related behaviors in OFT and EPM but not in depression-like behaviors in FST. Such behavioral differences could be related to an increased DOPAC concentration and 5-HT turnover in prefrontal cortex. These evidences suggest that natural variations in maternal care modified some behavioral and neurochemical parameters related with anxiety and stress in this strain. PMID:23711565

Masís-Calvo, Marianela; Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Fornaguera-Trías, Jaime



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

NASA Technical Reports Server (NTRS)

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.

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



Effect of maternal dietary amino acid pattern on rat offspring.  


The effect of lifetime feeding to gravid rats of diets containing different indispensable amino acid patterns on body and brain composition of the offspring was studied. Two groups of rats were fed, from weaning to delivery, either experimental diet B or diet I. Both diets contained the same amount of total nitrogen (3.14%), available lysine (0.4%) and "complete protein to total protein ratio" (22.5%), but whereas diet I provided an excess of indispensable amino acids over the amount of limiting amino acid, diet B supplied all of the indispensable amino acids in marginal amounts and in a rather well balanced pattern. The nitrogen content of diet B was matched to the nitrogen content of diet I by addition of a mixture of dispensable amino acids. A control group fed stock diet (C) was run simultaneously. Birth body weight, carcass nitrogen to water ratio, and brain weight of pups were significantly lower in B than in I. The figures for I were not significantly different from the controls. Brain DNA content in B was significantly lower than in C, but in I it was lower than for both B and C. Nitrogen to water ratio and brain DNA content of group B were low when compared to the standard curves for our colony; however, DNA content was normal for the degree of body development. On the other hand, in group I brain DNA was preferentially affected, as if body and brain maturity were dissociated. PMID:835505

Portela, M L; Rio, M E; Sanahuja, J C



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


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

Planeta, C S; Marin, M T



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

SciTech Connect

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.

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



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

PubMed Central

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 28–30 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.

Banihashemi, Layla; Rinaman, Linda



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


Maternal separation of rat pups for 15 min 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 JP, Levitt P, Gluhovsky M, Rinaman L (2005) J Neurosci 25(40):9102-9111]. 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 28-30 day old male rats with an earlier developmental history of either MS15 or NS. Rats were perfused 72 h 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

Banihashemi, L; Rinaman, L



Study on developmental abnormalities in hypospadiac male rats induced by maternal exposure to di- n-butyl phthalate (DBP)  

Microsoft Academic Search

The objective of this study was to establish a hypospadiac rat model by maternal exposure to di-n-butyl phthalate (DBP) and to evaluate the developmental abnormalities of hypospadiac male rats. Timed-pregnant rats were given DBP by gastric intubation at doses of 0, 250, 500, 750 or 1000mg\\/kg body weight (bw)\\/day from gestation day (GD) 14 to 18 to establish a hypospadiac

JunTao Jiang; Long Ma; Lin Yuan; XinRu Wang; Wei Zhang



Effects of maternal methyl-supplement diet on hippocampal glucocorticoid receptor mRNA expression in rats selected for behavior  

Microsoft Academic Search

In the present work, we study glucocorticoid receptor (GR) gene expression in gray rats selected for aggressive and domestic\\u000a behavior, as well as in offspring of mothers with methyl-supplemented diet during pregnancy. Tame selection is associated\\u000a with increased GR mRNA expression as compared with aggressive rats, whereas maternal methyl-supplemented diet inhibits GR\\u000a activity in tame rats. GR gene promoter methylation

Yu. E. Herbeck; I. N. Os’kina; R. G. Gulevich; I. Z. Plyusnina



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


Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. PMID:24632022

Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos



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

PubMed Central

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.

Aksic, Milan; Radonjic, Nevena V.; Aleksic, Dubravka; Jevtic, Gordana; Markovic, Branka; Petronijevic, Natasa; Radonjic, Vidosava; Filipovic, Branislav



Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain  

PubMed Central

Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD) produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach) release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE) activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS) cortex. Wistar rats were separated from their mothers on the postnatal day (P) 9 for 24?h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

Markovic, Branka; Radonjic, Nevena V.; Aksic, Milan; Filipovic, Branislav; Petronijevic, Natasa



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


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

Harvey, Louise; Boksa, Patricia



Relationship between maternal milk PGE2 and gastric acid secretion in newborn rats.  


We previously demonstrated that in rats gastric acid secretion declines after birth and drops steeply on day 12 of life. In the present study, we investigated the part played in this decline by prostaglandin E2 (PGE2) from maternal milk. PGE2 content was first measured in the milk of untreated dams 0, 1, 5, 10, 12, 15, and 18 days after parturition. PGE2 levels were high during the first 5 days (123.5-200.5 pg/ml), declined significantly between days 10 and 15 (56.6-85.4 pg/ml; P less than 0.05), and dropped to 18.4 pg/ml on day 18. We also found that depleting milk of PGE2 prevented drop of acid secretion in 12-day-old suckling rats. Injecting lactating dams with indomethacin significantly reduced milk PGE2 content by 65% vs. milk of untreated dams. Surprisingly, administration of sesame oil, the indomethacin vehicle to the dams, increased milk PGE2 content by 182%. In the pups of the indomethacin-treated dams, acid secretion did not drop. On the contrary, in vivo basal and histamine-induced acid output rose markedly by 40 and 50%, respectively, and in vitro the net movements of 36Cl and 22Na measured in the isolated stomach indicated that active Cl- secretion had resumed. Mucosal PGE2 did not appear to be significantly involved in early development of acid secretion because administration of indomethacin to pups from untreated dams did not significantly modify the secretion measured on day 12. Data indicate that maternal milk depletion of PGE2 prevents the drop of gastric acid secretion previously observed in 12-day-old pups and suggest that in infant rats maternal PGE2 plays a physiological part in regulating acid secretion. PMID:2240214

Wirbel, A; Ducroc, R; Garzon, B; Merlet-Bénichou, C; Geloso, J P



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


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

Marin, Marcelo T; Planeta, Cleopatra S



Excess of Methyl Donor in the Perinatal Period Reduces Postnatal Leptin Secretion in Rat and Interacts with the Effect of Protein Content in Diet  

PubMed Central

Methionine, folic acid, betaine and choline interact in the one-carbon metabolism which provides methyl groups for methylation reactions. An optimal intake of these nutrients during pregnancy is required for successful completion of fetal development and evidence is growing that they could be involved in metabolic long-term programming. However, the biological pathways involved in the action of these nutrients are still poorly known. This study investigated the interaction between methyl donors and protein content in maternal diet during the preconceptual, pregnancy and lactation periods and the consequences on the rat offspring in the short and long term. Methyl donor supplementation reduced leptin secretion in offspring, whereas insulin levels were mostly affected by protein restriction. The joint effect of protein restriction and methyl donor excess strongly impaired postnatal growth in both gender and long term weight gain in male offspring only, without affecting food intake. In addition, rats born from protein restricted and methyl donor supplemented dams gained less weight when fed a hypercaloric diet. Methylation of the leptin gene promoter in adipose tissue was increased in methyl donor supplemented groups but not affected by protein restriction only. These results suggest that maternal methyl donor supplementation may influence energy homeostasis in a gender-dependent manner, without affecting food intake. Moreover, we showed that macronutrients and micronutrients in maternal diet interact to influence the programming of the offspring.

Giudicelli, Fanny; Brabant, Anne-Laure; Grit, Isabelle; Parnet, Patricia; Amarger, Valerie



Maternal and fetal toxicity of N-methylmorpholine by oral administration in rats.  


N-methylmorpholine, which is used as a catalyst in polyurethane foams producing, in solvents, stabilizing agents, and corrosion inhibitors, was administered to female rats by gavage at 100, 200, 600, and 900 mg/kg during organogenesis. It did not exhibit selective toxicity toward the developing conceptus. This compound administered to pregnant females was fetotoxic and teratogenic in the presence of maternal toxicity. N-methylmorpholine induced anophthalmia, internal hydrocephalus, and hydronephrosis but only at one dose which was also maternotoxic. Teratogenesis Carcinog. Mutagen. 19:369-376, 1999. PMID:10587407

Sitarek, K



Developmental effects of boric acid in rats related to maternal blood boron concentrations  

Microsoft Academic Search

Timed-mated Sprague-Dawley rats (60\\/group) were exposed to boric acid (BA) from gestational days (gd) 0 to 20. BA added to\\u000a the diet (0, 0.025, 0.050, 0.075, 0.1, or 0.2%) yielded boron (B) intakes of <0.35 (control), 3, 6,10,13, or 25 mg B\\/kg body\\u000a wt\\/d. Approximately one-half of the dams\\/group were terminated on gd 20, maternal whole blood collected and frozen,

Catherine J. Price; Philip L. Strong; F. Jay Murray; Margaret M. Goldberg



Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats.  


Lamotrigine is an anticonvulsant and has an antiglutamatergic action, which may contribute to its antidepressant effects, since glutamate has been linked to depression. The purpose of the present study was to investigate the behavioral and molecular effects of lamotrigine treatment in maternally deprived rats. To this aim, deprived and non-deprived male rats were treated with lamotrigine (20 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed in the forced swimming and open field tests. In addition to this, the BDNF and NGF levels were assessed in the prefrontal cortex, hippocampus and amygdala. In the course of this study we demonstrated that maternally deprived rats treated with saline and lamotrigine showed an increase in their immobility time and a decrease in the climbing and swimming times when compared with non-deprived rats treated with saline alone. Treatment with lamotrigine reversed the increase in the immobility time in the deprived rats. The BDNF levels were decreased in the amygdala in deprived rats treated with saline, and treatment with lamotrigine reversed this decrease. The NGF levels were decreased in the hippocampus in deprived rats treated with saline, but treatment with lamotrigine did not reverse this decrease. In conclusion, lamotrigine showed antidepressant effects in the forced swimming test, and it presented positive effects on the BDNF protein levels in the amygdala of maternally deprived rats. PMID:22306746

Abelaira, Helena M; Réus, Gislaine Z; Ribeiro, Karine F; Zappellini, Giovanni; Cipriano, Andreza L; Scaini, Giselli; Streck, Emilio L; Quevedo, João



Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice  

PubMed Central

The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-? hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation.

Garbrecht, Mark R.; Lamb, Fred S.



Differential effects of short- and long-term early maternal separation on subsequent maternal behavior in rats.  


ABSTRACT Female Sprague-Dawley pups were separated from mothers every other day for 8 hr (long-term separation/LTS), 4 hr (short-term separation/STS), or 0 hr (no separation/NS) from postnatal day 2-20. In adulthood, they were mated and tested for maternal behaviors during two lactations. It was expected that females separated from mothers as pups would show deficits in maternal behavior as adults. Contrary to expectations, LTS showed better nest building and grouped young faster during both lactations. LTS were first to display aggression and displayed more aggression during the second lactation. Notably, while some measures decreased from first to second lactation in NS and STS, LTS maintained levels of maternal care. These results suggest that extended periods of maternal separation may exaggerate some aspects of maternal behavior. PMID:24836911

Bodensteiner, Karin J; Ghiraldi, Loraina L; Miner, Stephanie S



Natural variation in maternal care shapes adult social behavior in rats.  


Features of the early postnatal environment profoundly shape later physical and behavioral phenotypes. The amount of licking/grooming that rat dams direct towards their offspring has durable consequences, including behavioral and physiological dimensions of stress reactivity, cognition, and reproductive behavior. We examined how natural variation in maternal care alters social behavior in adult offspring and how this relates to anxiety behavior and oxytocin receptor density. Male and female offspring of mothers who received high levels of licking spent significantly more time in social contact with unfamiliar individuals than did offspring whose dams provided less grooming. Reduced anxiety behavior was associated with greater social interaction. No differences in oxytocin receptor binding assessed by (125) I-OVTA autoradiography were detected between groups. The present investigation characterizes a novel impact of maternal care on adult social interaction behavior, replicates anxiety behavior differences, and illustrates connections between social behavior and anxiety in adulthood across maternal treatment groups. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 1017-1026, 2014. PMID:24271510

Starr-Phillips, Emily J; Beery, Annaliese K



Effect of maternal cholestasis on biliary lipid and bile acid secretion in the infant rat.  


Partial and reversible impairment of bile formation has been reported to occur in the offspring of rats undergoing common bile duct ligation during the last third of pregnancy. This situation was defined as latent cholestasis of the neonate and was suggested to be related to the multilamellar bodies partially occupying the canalicular lumen. The current study was undertaken to investigate the presence of alterations in the secretion of biliary lipids in these infant rats. Using both high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses, no changes caused by maternal cholestasis were found in either the conjugation pattern, or in the ratio of primary to secondary major bile acids in bile samples collected from 4-week-old and 8-week-old rats. However, a decrease in the proportion of cholate together with an increase in the amount of alpha- and omega-muricholate were found at 4 weeks of age. These changes were different from those observed in the pattern of maternal plasma bile acids, in which beta-, but not alpha-muricholate, concentrations were increased. Moreover, studies performed by labeling the bile acid pool of the cholestatic mother-fetus tandem with [14C]glycocholic acid (GC) at day 16 of pregnancy indicated that only a minor proportion (approximately 10%) of bile acids found in 4-week-old pups was of maternal origin. Changes in the bile acid pool composition were fully reversed by 8 weeks of age. Bile lecithin and cholesterol output were determined by enzymatic techniques, both under basal conditions and during stepwise taurocholate (TC) infusion. At the time when multilamellar bodies were found, i.e., 4 weeks after birth, no change in either nonstimulated or TC-induced cholesterol output was observed. By contrast, both spontaneous and TC-induced lecithin secretion were markedly higher (+200%) in pups of cholestatic mothers as compared with control rats. These differences were abolished at 8 weeks of age. At this time, cholesterol output was significantly lower than that found in younger animals. This reduction was more pronounced in the control than in the cholestatic group. Histological examination of liver samples collected from the cholestatic group at 4 weeks of age revealed the presence of multilamellar bodies not only in the canalicular lumen but also within vesicular structures located in the pericanalicular area or near the Golgi apparatus. Both intracellular and intracanalicular bodies were present before and after TC infusion for 2 hours. These results indicate that maternal cholestasis in rats induces profound alterations in biliary lipids and bile acid secretion in their pups. Because bile acids are important activators of different steps responsible for biliary lipid secretion (intracellular trafficking, releasing into bile, and solubilization), alterations in maternal bile acid pool size and composition may affect the fetal development of biliary lipid secretion mechanisms, which may result in the appearance of multilamellar bodies within bile canaliculi, which in turn may be involved in the reversible latent cholestasis observed in these infants rats. PMID:9303479

El-Mir, M Y; Monte, M J; Morales, A I; Arevalo, M; Serrano, M A; Marin, J J



Maternal Rat Diabetes Mellitus Deleteriously Affects Insulin Sensitivity and Beta-Cell Function in the Offspring  

PubMed Central

This study was designed to assess the effect of maternal diabetes in rats on serum glucose and insulin concentrations, insulin resistance, histological architecture of pancreas and glycogen content in liver of offspring. The pregnant rat females were allocated into two main groups: normal control group and streptozotocin-induced diabetic group. After birth, the surviving offspring were subjected to biochemical and histological examination immediately after delivery and at the end of the 1st and 2nd postnatal weeks. In comparison with the offspring of normal control dams, the fasting serum glucose level of offspring of diabetic mothers was significantly increased at the end of the 1st and 2nd postnatal weeks. Serum insulin level of offspring of diabetic dams was significantly higher at birth and decreased significantly during the following 2 postnatal weeks, while in normal rat offspring, it was significantly increased with progress of time. HOMA Insulin Resistance (HOMA-IR) was significantly increased in the offspring of diabetic dams at birth and after 1 week than in normal rat offspring, while HOMA insulin sensitivity (HOMA-IS) was significantly decreased. HOMA beta-cell function was significantly decreased at all-time intervals in offspring of diabetic dams. At birth, islets of Langerhans as well as beta cells in offspring of diabetic dams were hypertrophied. The cells constituting islets seemed to have a high division rate. However, beta-cells were degenerated during the following 2 post-natal weeks and smaller insulin secreting cells predominated. Vacuolation and necrosis of the islets of Langerhans were also observed throughout the experimental period. The carbohydrate content in liver of offspring of diabetic dams was at all-time intervals lower than that in control. The granule distribution was more random. Overall, the preexisting maternal diabetes leads to glucose intolerance, insulin resistance, and impaired insulin sensitivity and ?-cell function in the offspring at different postnatal periods.

Aref, Abdel-Baset M.; Ahmed, Osama M.; Ali, Lobna A.; Semmler, Margit



Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions.  


Bauhinia forficata, commonly known as "paw-of-cow", is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation. PMID:15070172

Damasceno, D C; Volpato, G T; Calderon, I de Mattos Paranhos; Aguilar, R; Rudge, M V Cunha



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


Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6-20 (during organogenesis and fetal development period) at doses of 3, 6 and 9mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring. PMID:24881561

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



Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression.  


Genetic predisposition and stress are major factors in depression. The objective of this study was to establish a robust animal model of depression by selecting the appropriate substrain of the Wistar-Kyoto (WKY) rat, and subjecting these rats to the stress of maternal separation during the early stages of development. The initial experiment identified WKY/NCrl as the appropriate substrain of WKY to use for the study. In the second part of the study, depression-like behavior and ultrasonic vocalizations (USVs) were recorded in WKY/NCrl and maternally separated WKY/NCrl rats during the course of reversal of depression-like behavior. Wistar rats served as the reference strain. In adulthood, non-separated WKY/NCrl, maternally separated WKY/NCrl and Wistar rats were injected intraperitoneally with either saline or desipramine (15 mg/kg/day) for 15 days and their behavior recorded. Desipramine decreased immobility and increased active swimming and struggling behavior of WKY/NCrl in the FST and also decreased their USVs in response to removal of cage mates. The USVs in this study appeared to signal an attempt to re-establish social contact with cage mates and provided a measure of social dependence. Maternally separated WKY/NCrl rats displayed more anxiety than normally reared WKY/NCrl rats and responded to the anxiolytic effects of desipramine. The present findings support the use of WKY/NCrl as an animal model of depression. Maternal separation increased the anxiety-like behavior of the WKY/NCrl, thus providing a robust model to study depression- and anxiety-related behavior. PMID:24338028

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



Both maternal over- and undernutrition during gestation increase the adiposity of young adult progeny in rats.  


We examined the influence of maternal diet during gestation on the growth and body composition of the progeny. On day 1 of gestation, rat dams were assigned to one of four feeding regimens: free access to standard rodent chow throughout gestation (AL); 20 g feed/day (prebreeding intake) throughout gestation (PB); 10 g feed/day from day 1 to day 14, then ad libitum from day 15 to parturition (RAL); 10 g feed/day from day 1 to 14, then 20 g/day to parturition (RPB). Progeny were fed ad libitum on standard chow diet from 3 to 12 weeks of age; food intake and weight gain were measured over this time. Body composition was measured at 12 weeks. The PB regimen restricted maternal food intake during the third trimester only; the RAL regimen restricted intake by 50% for two trimesters and produced hyperphagia in the third; the RPB regimen restricted intake by 50% for two trimesters, then intake (per unit body weight) was similar to that of AL dams during the third trimester. Litter size and progeny birth, weaning, and 12-week body weights were similar among the four groups. At 12 weeks of age, PB progeny had the highest body fat (per kg fat-free mass), despite similar feed intake during the 9-week postweaning period. The increased fat was proportionally distributed among intra-abdominal and subcutaneous depots. Progeny of RAL, AL, and RPB dams had similar amounts of body fat, but in RAL progeny more fat was present in intra-abdominal depots. The weights of fat-free mass, gastrointestinal tract and hindlimb skeletal muscles were unaffected by maternal diet. Restriction of maternal feed intake during the third week of gestation had subtle effects on the body composition of young adult progeny that could not be explained on the basis of differences in postweaning voluntary feed intake. PMID:7719959

Fiorotto, M L; Davis, T A; Schoknecht, P; Mersmann, H J; Pond, W G



Molecular Patterns of Neurodevelopmental Preconditioning: A Study of the Effects of Antenatal Steroid Therapy in a Protein-Restriction Mouse Model  

PubMed Central

Introduction. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. Methods. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100??g/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10–E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. Results. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. Conclusion. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols.

Ito, Takuya; Endo, Miyuki; Funamoto, Kiyoe; Yaegashi, Nobuo



Effect of maternal separation on mitochondrial function and role of exercise in a rat model of Parkinson's disease.  


Early life stress, such as maternal separation, causes adaptive changes in neural mechanisms that have adverse effects on the neuroplasticity of the brain in adulthood. As a consequence, children who are exposed to stress during development may be predisposed to neurodegenerative disorders in adulthood. A possible mechanism for increased vulnerability to neurodegeneration may be dysfunctional mitochondria. Protection from neurotoxins, such as 6-hydroxydopamine (6-OHDA), has been observed following voluntary exercise. The mechanism of this neuroprotection is not understood and mitochondria may play a role. The purpose of this study was to determine the effects of maternal separation and exercise on mitochondrial function in a rat model of Parkinson's disease. Maternally separated (pups separated from the dam for 3 h per day from postnatal day (P) 2-14) and non-separated rats were placed in individual cages with or without attached running wheels for 1 week prior to unilateral infusion of 6-OHDA (5 ?g/4 ?l, 0.5 ?l/min) into the left medial forebrain bundle at P60. After 2 h recovery, rats were returned to their cages and wheel revolutions recorded for a further 2 weeks. On P72, the rats' motor function was assessed using the forelimb akinesia test. On P74, rats were sacrificed for measurement of mitochondrial function. Exercise increased the respiratory control index (RCI) in the non-lesioned hemisphere of 6-OHDA-lesioned rats. This effect was evident in the striatum of non-separated rats and the prefrontal cortex of maternally separated rats. These results suggest that early life stress may reduce the adaptive response to exercise in the striatum, a major target of dopamine neurons, but not the prefrontal cortex in this model of Parkinson's disease. PMID:22527997

Hendricks, Sharief; Ojuka, Edward; Kellaway, Lauriston A; Mabandla, Musa V; Russell, Vivienne A



The effects of the wood preservative copper dimethyldithiocarbamate in the hippocampus of maternal and newborn Long-Evans rats  

Microsoft Academic Search

The potential toxic effects on human health and deleterious effects to the environment by copper dimethyldithiocarbamate (CDDC), an alternative wood preservative to chromated copper arsenate (CCA) have not been investigated. This study describes the neurotoxicity and accumulation of copper in the hippocampus of maternal and newborn Long-Evans rats following a subacute exposure to CDDC. Pregnant rats (220–270g) were treated daily

Brian Scharf; Louis David Trombetta



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

PubMed Central

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.

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



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


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

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



Maternal dietary exposure to fiber during pregnancy and mammary tumorigenesis among rat offspring.  


Maternal diet during pregnancy has been proposed to modify female offspring's later susceptibility to develop breast cancer; however, most of the dietary factors identified thus far have led to increased risk. To identify dietary factors that might reduce offspring's breast cancer risk, pregnant rat dams were fed diets containing 6% fiber originating either from cellulose (control), or oat, whole wheat or defatted flax flour. At birth, dams were switched to the AIN93 semi-purified diet. Mammary tumor incidence and multiplicity, induced by administering the offspring 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) at the age of 50 days, was reduced in the whole wheat flour-exposed offspring and increased in the defatted flax-exposed offspring. To identify the mechanisms mediating the effects of in utero dietary exposures, changes in mammary gland morphology and gene expression were assessed before puberty onset (3 weeks of age) and at the time rats are most susceptible to malignant transformation (8 weeks of age). The number of terminal end buds (TEBs), i.e., the targets of malignant transformation, was reduced in the mammary glands of whole wheat- and oat flour-exposed offspring, as compared to the controls. Further, the number of apoptotic epithelial cells (based on ISOL assay) was elevated in the whole wheat flour offspring, but no changes in cell proliferation (PCNA), estrogen receptor alpha (ER-alpha) or cyclin D1 mRNA or protein levels were seen. The mRNA and/or protein levels of BRCA1 and p53 were significantly increased in the mammary glands of whole wheat flour offspring. Further, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA damage, were significantly reduced in these rats, suggesting that maternal dietary exposure to whole wheat during pregnancy may reduce offspring's breast cancer risk by improving DNA damage repair mechanisms. PMID:16921499

Yu, Bin; Khan, Galam; Foxworth, Aaron; Huang, Kai; Hilakivi-Clarke, Leena



Prenatal exposure to maternal voluntary exercise during pregnancy provides protection against mild chronic postnatal hypoxia in rat offspring.  


Postnatal hypoxia is a main cause of neuronal damage in newborn. However, our understanding of the possible preventive or therapeutic methods to reduce the harmful effects of hypoxia is still primary. Pregnant rats were provided with running wheels during their pregnancy. On PND4 (postnatal day 4)to PND8, the rat pups were exposed to postnatal chronic hypoxia (11% O(2), 89% N(2)) in an air-tight plastic chamber for a period of six hours per day. The number of neurons and also angiogenesis in hippocampus were studied. Postnatal exposure to mild hypoxia decreased the number of the neurons in all studied regions of the hippocampus CA1, CA3 (cornu ammonis), DG(dentate gyrus) and SUB(cubiculum) in rat pups. In other words the number of the neurons in rat pups born from voluntary exercise group was not significantly less than control group in CA1, CA3 and DG regions. So maternal Voluntary exercise during pregnancy increases the blood vessel density in the DG region of the hippocampus of the rat pups. In this study for the first time we provide evidences that show the protective effect of maternal voluntary exercise during pregnancy on rat offspring against postnatal hypoxia. We revealed that maternal exercise during pregnancy increases the hippocampal neuron number and angiogenesis in offspring. PMID:22186335

Akhavan, Maziar Mohammad; Foroutan, Tahereh; Safari, Manouchehr; Sadighi-Moghaddam, Bizhan; Emami-Abarghoie, Mitra; Rashidy-Pour, Ali



Maternal care counteracts behavioral effects of prenatal environmental stress in female rats.  


There is extensive evidence in rats that prenatal environmental stress (PES) exposure and early postnatal altered maternal care, as a consequence of stress during gestation, can detrimentally affect the brain and behavioral development of the offspring. In order to separate the effect of PES on the fetuses from that on the behavior of the mother, in the present study, we used a cross-fostering procedure in which PES-fetuses were raised by non-stressed mothers and non PES-fetuses were raised by stressed mothers. In Experiment 1, non-stressed mothers showed significantly more maternal behavior than stressed mothers. In Experiment 2, when the female offspring from Experiment 1 reached maturity, they were tested for: (1) induced maternal behavior (MB), (2) plasma levels of corticosterone (Cpd B), progesterone (P), and estradiol (E(2)), (3) number of accessory olfactory bulb (AOB) mitral cells, and (4) c-fos expression measured in AOB and medial preoptic area (MPOA) neurons. We replicated our previous findings that the PES group reared by their own stressed mothers, when adult, attacked the young, expressed disorganized MB and showed altered Cpd B, P and E(2) levels, plus a male-like neuro-morphological pattern in the AOB, by comparison with the non-PES group, reared by their own non-stressed mothers. By contrast, when adult, the PES group reared by non-stressed mothers showed hormonal and morphological neuronal alterations, but they displayed appropriate (full) MB. The non-PES group raised by stressed mothers also showed altered hormone levels, but showed full MB and no morphological neuronal changes. Significant differences in the AOB and MPOA c-fos activity, related to whether or not MB was expressed, were found in the non-PES groups, but not in the PES group reared by non-stressed mothers. To our knowledge, this is the first study to document that adequate maternal care, early in development, can shape the subsequent expression of induced MB, overcoming neuro-morphological and hormonal alterations that are produced by prenatal environmental stress. We conclude that maternal care during early postnatal development can counteract detrimental effects of prenatal environmental stress, exerting long-lasting effects that modulate the behavioral phenotype of the offspring. PMID:20079763

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



Does prolonged protein restriction preceding dialysis lead to protein malnutrition at the onset of dialysis?  

Microsoft Academic Search

Does prolonged protein restriction preceding dialysis lead to protein malnutrition at the onset of dialysis? It has recently been suggested that prolonged protein restriction preceding dialysis may induce protein malnutrition and thus confer a poor prognosis during dialysis. We examined the records of all patients who were prescribed a very low protein diet (0.3 g\\/kg ideal body weight) plus supplemental

Mackenzie Walser



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

PubMed Central

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. ?-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.

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.



Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic ?-cell function during pregnancy.  


Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in ?-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and ?-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-? activity in islets from the RP and LPP rats. Protein kinase C (PKC)-? but not phospholipase C (PLC)-?1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. PMID:22475371

Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz



Neonatal maternal separation and sex-specific plasticity of the hypoxic ventilatory response in awake rat  

PubMed Central

We tested the hypothesis that neonatal maternal separation (NMS), a form of stress that affects hypothalamo–pituitary–adrenal axis (HPA) function in adult rats, alters development of the respiratory control system. Pups subjected to NMS were placed in a temperature and humidity controlled incubator 3 h per day for 10 consecutive days (P3 to P12). Control pups were undisturbed. Once they reached adulthood (8–10 weeks old), rats were placed in a plethysmography chamber for measurement of ventilatory and cardiovascular parameters under normoxic and hypoxic conditions (FIO2 = 0.12). Measurement of c-fos mRNA expression in the paraventricular nucleus of the hypothalamus (PVH) combined with plasma ACTH and corticosterone levels confirmed that NMS effectively disrupted HPA axis function in males. In males, baseline minute ventilation was not affected by NMS. In contrast, NMS females show a greater resting minute ventilation due to a larger tidal volume. The hypoxic ventilatory response of male NMS rats was 25% greater than controls, owing mainly to an increase in tidal volume response. This augmentation of the hypoxic ventilatory response was sex-specific also because NMS females show an attenuated minute ventilation increase. Baseline mean arterial blood pressure of male NMS rats was 20% higher than controls. NMS-related hypertension was not significant in females. The mechanisms underlying sex-specific disruption of cardio-respiratory control in NMS rats are unknown but may be a consequence of the neuroendocrine disruption associated with NMS. These data indicate that exposure to a non-respiratory stress during early life elicits significant plasticity of these homeostatic functions which persists until adulthood.

Genest, Sophie-Emmanuelle; Gulemetova, Roumiana; Laforest, Sylvie; Drolet, Guy; Kinkead, Richard



Maternal caffeine consumption has irreversible effects on reproductive parameters and fertility in male offspring rats  

PubMed Central

Objective Concerns are growing about the decrease in male reproductive health. Caffeine is one of the popular nutrients that has been implicated as a risk factor for infertility. In the present study, we examined whether in utero and lactational exposure to caffeine affects the reproductive function of the offspring of rats. Methods Pregnant rats received caffeine via drinking water during gestation (26 and 45 mg/kg) and lactation (25 and 35 mg/kg). Body and reproductive organ weight, seminiferous tubule diameter, germinal epithelium height, sperm parameters, fertility rate, number of implantations, and testosterone level of the offspring were assessed from birth to adulthood. Results Significant dose-related decreases were observed in the body and reproductive organ weight, seminiferous tubule diameter, and germinal epithelium height of the offspring. Sperm density had declined significantly in offspring of the low-dose and high-dose groups, by 8.81% and 19.97%, respectively, by postnatal day 150. The number of viable fetuses had decreased significantly in females mated with male offspring of the high-dose group at postnatal days 60, 90, 120, and 150. There were also significant reductions in testosterone levels of high-dose group offspring from birth to postnatal day 150. Conclusion It is concluded that maternal caffeine consumption impairs gonadal development and has long-term adverse effects on the reproductive efficiency of male offspring rats.

Erfani Majd, Naeem; Nooraei, Parvaneh



Maternal allergen exposure reprograms the developmental lung transcriptome in atopic and normoresponsive rat pups  

PubMed Central

The “fetal origins hypothesis” argued that physiological changes consequent to in utero exposures ultimately contribute to disease susceptibility in later life. The dramatic increase in asthma prevalence is attributed to early exposures acting on preexisting asthma-susceptible genotypes. We showed previously that distinct transcriptome signatures distinguish the developmental respiratory phenotype of atopic (Brown Norway, BN) and normoresponsive (Lewis) rats. We aimed to determine whether maternal allergen exposure would influence asthma pathogenesis by reprogramming primary patterns of developmental lung gene expression. Postnatal offspring of dams sensitized to ovalbumin before mating and challenged during pregnancy were assessed for lung function, inflammatory biomarkers, and respiratory gene expression. Although maternal ovalbumin exposure resulted in characteristic features of an allergic response (bronchoalveolar lavage neutrophils, IgE, methacholine-induced lung resistance) in offspring of both strains, substantial strain-specific differences were observed in respiratory gene expression. Of 799 probes representing the top 5% of transcriptomic variation, only 112 (14%) were affected in both strains. Strain-specific gene signatures also exhibited marked differences in enrichment for gene ontologies, with immune regulation and cell proliferation being prominent in the BN strain, cell cycle and microtubule assembly gene sets in the Lewis strain. Multiple ovalbumin-specific probes in both strains were also differentially expressed in lymphoblastoid cell lines from human asthmatic vs. nonasthmatic sibling pairs. Our data point to the existence of distinct, genetically programmed responses to maternal exposures in developing lung. These different response patterns, if recapitulated in human fetal development, can contribute to long-term pulmonary health including interindividual susceptibility to asthma.

Carpe, Nicole; Mandeville, Isabel; Kho, Alvin T.; Qiu, Weiliang; Martin, James G.; Tantisira, Kelan G.; Raby, Benjamin A.; Weiss, Scott T.



Combined Norepinephrine/Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression, and Oxytocin in the Rat  

PubMed Central

Background: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior (MB), although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent MB in rodents indicated significant alterations in postpartum maternal care, aggression, and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on MB, aggression, and oxytocin system changes. Methods: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. MB and postpartum aggression were assessed on postpartum days 1 and 6 respectively. Oxytocin levels were measured in relevant brain regions on postpartum day 7. Predictions were that amitriptyline would decrease MB and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. Results: Amitriptyline and desipramine differentially reduced MB, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in maternal care.

Cox, Elizabeth Thomas; Jarrett, Thomas Merryfield; McMurray, Matthew Stephen; Greenhill, Kevin; Hofler, Vivian E.; Williams, Sarah Kaye; Joyner, Paul Wayland; Middleton, Christopher L.; Walker, Cheryl H.; Johns, Josephine M.



Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood  

PubMed Central

Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero.

Krstew, Elena V.; Tait, Robert J.; Hulse, Gary K.



Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats.  


Although sleep complaints are very common among pregnant women, the potential adverse effects of sleep disturbance on the offspring are not well studied. Growing evidence suggests that maternal stress can induce an inflammatory environment on the fetal development. But people are not sure about the consequences of prenatal stress such as the inflammatory responses induced by maternal sleep deprivation (MSD). In the present study, we investigated the effects of MSD on long-term behavioral and cognitive consequences in offspring and its underlying inflammatory response pathway. The pregnant Wistar rats received prolonged sleep deprivation (72h) on gestational day (GD) 4, 9, and 18, respectively. The post-natal day (PND) 21 offspring showed impaired hippocampus-dependent spatial learning and memory in the Morris Water Maze task and anhedonia in sucrose preference experiment. Quantification of BrdU(+) and DCX(+) cells revealed a significant decrease in hippocampus neurogenesis in prepuberty offspring, especially for the late MSD (GD 18) group. Real-time RT-PCR showed that after MSD, the expression of pro-inflammatory cytokines (IL-1?, IL-6 and TNF?) increased in the hippocampus of offspring on PND 1, 7, 14 and 21, whereas anti-inflammatory cytokine IL-10 reduced at the same time. Immunofluorescence found that the cells of activated microglia were higher in the brains of MSD offspring. Taken together, these results suggested that the MSD-induced inflammatory response is an important factor for neurogenesis impairment and neurobehavioral outcomes in prepuberty offspring. PMID:24769004

Zhao, Qiuying; Peng, Cheng; Wu, Xiaohui; Chen, Yubo; Wang, Cheng; You, Zili



Fetal iron status regulates maternal iron metabolism during pregnancy in the rat.  


Iron metabolism during pregnancy is biased toward maintaining the fetal supply, even at the cost of anemia in the mother. The mechanisms regulating this are not well understood. Here, we examine iron deficiency and supplementation on the hierarchy of iron supply and the gene expression of proteins that regulate iron metabolism in the rat. Dams were fed iron-deficient diets for 4 wk, mated, and either continued on the deficient diet or an iron-supplemented diet during either the first half or the second half of their pregnancy. A control group was maintained on normal iron throughout. They were killed at 0.5, 12.5, or 21.5 days of gestation, and tissues and blood samples were collected. Deficiency and supplementation had differential effects on maternal and fetal hematocrit and liver iron levels. From early in pregnancy, a hierarchy of iron supply is established benefiting the fetus to the detriment of the mother. Transferrin receptor, transferrin receptor 2, and hepcidin mRNA expression were regulated by both iron deficiency and supplementation. Expression patterns showed both organ and supplementation protocol dependence. Further analysis indicated that iron levels in the fetal, and not maternal, liver regulate the expression of liver transferrin receptor and hepcidin expression in the mother. PMID:19176888

Gambling, Lorraine; Czopek, Alicja; Andersen, Henriette S; Holtrop, Grietje; Srai, S Kaila S; Krejpcio, Zbigniew; McArdle, Harry J



Altered arginine metabolism in the hippocampus and prefrontal cortex of maternal immune activation rat offspring.  


Altered arginine metabolism has been implicated in the pathogenesis of schizophrenia. The present study measured the levels of L-arginine and its downstream metabolites in the sub-regions of the hippocampus, prefrontal cortex and cerebellum in adult rats that had been exposed to maternal immune activation (MIA; a risk factor for schizophrenia). MIA significantly increased L-arginine, L-ornithine and putrescine levels and decreased agmatine levels in the hippocampus and prefrontal cortex in a region-specific manner. Correlational analysis revealed a significant neurochemical-behavioural correlation. Cluster analyses showed that L-arginine and its main metabolites formed distinct groups, which changed as a function of MIA. These results demonstrate, for the first time, that MIA leads to altered arginine metabolism in the hippocampus and prefrontal cortex of the adult offspring. PMID:23806581

Jing, Yu; Zhang, Hu; Wolff, Amy R; Bilkey, David K; Liu, Ping



Effects of maternal ethanol consumption on hematopoietic cells in the rat fetal liver.  


During development, there are many factors to be considered in studying the efficacy of the hematopoietic system to provide the immune system with adequate numbers of functional cells within the immune repertoire. Hematopoietic cells must be able to develop, proliferate, and emigrate from the hematopoietic fetal liver to other tissues of the body, such as the thymus and bone marrow. There is evidence that ethanol consumption causes immune deficiencies in adults and that maternal ethanol consumption causes immune deficiencies in children, both with correlative effects on cells and cytokinetic regulators. Therefore, the ability of the hematopoietic system to seed the immune system may be jeopardized by maternal ethanol consumption. In this study, test groups included female rats (1). fed a Lieber-DeCarli ethanol liquid diet, (2). pair-fed a control liquid diet, or (3). fed standard laboratory chow. Livers were removed from fetuses 18 and 21 days postconception (dpc) and analyzed by immunophenotyping and flow cytometry. There was a 22% and 38% decrease in fetal body weight and a 25% and 30% decrease in fetal liver weights between ethanol-fed and pair-fed groups at 18 and 21 dpc, respectively. At 18 dpc, fetal body and liver weights of the pair-fed animals were also significantly reduced to those of the chow-fed group. However, by 21 dpc, both body and liver weights of the two control groups were not statistically different. The effects of maternal ethanol consumption on the distribution of hematopoietic cells were characterized by using monoclonal antibodies (mAbs) anti-CD43 (a progenitor hematopoietic cell marker) versus labeling with anti-Vbeta8.2 (pre-T cells), anti-B220 (pre-B cells), and anti-NKR-P1A (pre-natural killer cells). With the use of flow cytometric analysis, at 18 dpc ethanol-exposed fetuses showed 40% and 62% decreases in B220(+) and Vbeta8.2(+) cells, respectively, versus findings for pair-fed controls, with no significant change in NKR-P1A(+) cells. At 21 dpc, ethanol-exposed fetuses showed a 46% decrease in B220(+) cells among the CD43(+) cells, with a 50% increase in Vbeta8.2(+) cells. Observed alterations in gross fetal body and liver weights, together with modifications in the percentage of hematopoietic cells in the fetal liver after maternal ethanol consumption, strongly support the suggestion that the ability of the hematopoietic system to impart a repertoire of cells that are functional in the regulatory and effector mechanisms of the immune process may be compromised. PMID:12551756

Robinson, Regina S; Seelig, Leonard L



Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.  


Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to maternal swimming. In conclusion, maternal swimming exercise induced neurometabolic programing in the offspring that could be of benefit to the rats against future cerebral insults. PMID:23639877

Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C



The timing of maternal separation affects morris water maze performance and long-term potentiation in male rats.  


The increasing evidences showed that adverse early life events have profound long lasting consequences in adult rats including neural, behavioral, and cognitive effects. Early maternal separation was one of the models of adverse early life stress, but which period acts critically was unknown until now. The purpose of this paper was to explore the effects of maternal separation in different periods, that is, postnatal Day 2-9 and postnatal Day 14-21, on spatial learning and memory and long-term potentiation (LTP) in hippocampus of adolescent rats. Rat pups were assigned to three groups: early maternal separation from postnatal Day 2-9 (EMS2-9), separation from postnatal Day 14-21 (EMS14-21), and control (Con)-rats stayed with their mother all the time before weaning. Morris water maze test (MWM) and electrophysiological test were performed at 40-50 days of age. The results indicated that EMS14-21 impaired spatial learning and memory ability. For the excitatory postsynaptic potential long-term potentiation (EPSP LTP), both the two maternal separation groups showed decreased values compared to control group. In terms of population spike long-term potentiation (PS LTP), both the two maternal separation groups also showed lower values compared with control group, but only EMS14-21 group had significant difference compared with control group. In conclusion, our results revealed that EMS14-21 showed worst in both escape latency in Morris Water Maze test and LTP compared to control group and EMS2-9 group. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 1102-1109, 2014. PMID:23712516

Cao, Xiujing; Huang, Shenghai; Cao, Jiejie; Chen, Tingting; Zhu, Ping; Zhu, Rui; Su, Puyu; Ruan, Diyun



Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  

Microsoft Academic Search

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in

Asmita Kulkarni; Kamini Dangat; Anvita Kale; Pratiksha Sable; Preeti Chavan-Gautam; Sadhana Joshi; Takeo Yoshikawa



Chemically induced alterations in maternal homeostasis and histology of conceptus: their etiologic significance in rat fetal anomalies.  


Possible relationships between maternal acid-base-electrolyte imbalance, histological changes in the maternal/extraembryonic tissues (decidua, placenta, membranes enclosing cavities), and fetal anomalies induced by maternotoxic doses of ethylene glycol, sodium salicylate, and cadmium chloride in rats were investigated. Acid-base-electrolyte, histologic and, teratologic studies were conducted concurrently with, as far as feasible, a similar protocol. Ethylene glycol caused 1) maternal homeostatic changes including metabolic acidosis and hyperosmolality, 2) extraembryonic lesions with degeneration of allantois and reduced villigenesis being more prevalent, and 3) materno-fetal effects such as decreases in fetal and maternal body weights, decreased maternal food intake, and fetal abnormalities (vertebral, rib, and sternebral defects). Few of these changes occurred when NaHCO3, an endogenous agent known to correct metabolic acidosis, was coadministered with ethylene glycol. Ethylene glycol-induced maternal metabolic acidosis, concurrent with hyperosmolality, was suspected to contribute toward reduction in villigenesis and fetal anomalies, including body weight reductions. Sodium salicylate induced the following: 1) mild maternal acidosis, hypokalemia, and hypophosphatemia with no significant change in pH; 2) maternal hemorrhage in extraembryonic cavities, papillary proliferation of the visceral yolk sac endoderm, and failure to form the chorioallantoic labyrinth; and 3) resorptions, hydrocephaly, rib defects, and fetal body weight reduction. Upon simultaneous treatment with sodium salicylate, NaHCO3 significantly reduced, and NH4Cl enhanced the incidence of the above histologic and teratologic effects, without significantly altering acid-base values. An etiologic association between the above salicylate-induced maternal and extraembryonic lesions and teratogenicity was likely. Cadmium chloride, whether administered by the intraperitoneal (ip) or intravenous (iv) route, caused 1) hydrocephaly, anophthalmia, vertebral and rib defects, reduction in fetal body weight, resorptions and maternal toxicity (acute peritonitis by the ip route only), and 2) extensive necrosis and hemorrhage in the decidua basalis, hemorrhage in the ectoplacental cone and around Reichert's membrane, and absence of chorioallantoic labyrinth. An etiologic relationship between these teratologic and histologic effects seemed probable, since both were dose-related. From the above studies, it was hypothesized that maternal factors--metabolic acidosis, hyperosmolality, hemorrhages in the ectoplacental cone, extraembryonic cavities, and around Reichert's membrane, and necrosis of decidua basalis--may have, directly or indirectly, reduced fetal nutrition and materno-embryonic gaseous exchange, which ultimately altered fetal development. PMID:1948764

Khera, K S



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


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

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



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


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

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



Measurement of somatomedin-related peptides in fetal, neonatal, and maternal rat serum by insulin-like growth factor (IGF) I radioimmunoassay, IGF-II radioreceptor assay (RRA)  

Microsoft Academic Search

Previous measurements of somatomedins (Sms) and insulin-like growth factors (IGFs) in maternal and fetal serum have yielded contradictory results. We have, therefore, measured maternal, fetal, and neonatal rat serum with two highly specific assays: 1) IGF-I\\/Sm-C RIA and 2) a highly specific IGF-II\\/rat placental membrane radioreceptor assay (RRA). In addition, we have made measurements with a less specific multiplication-stimulating activity

W. H. Daughaday; K. A. Parker; S. Borowsky; B. Trivedi; M. Kapadia



The phosphodiesterase type-5 inhibitor, tadalafil, improves depressive symptoms, ameliorates memory impairment, as well as suppresses apoptosis and enhances cell proliferation in the hippocampus of maternal-separated rat pups.  


Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups. PMID:21056623

Baek, Sang-Bin; Bahn, Geonho; Moon, Su-Jin; Lee, Jiah; Kim, Khae-Hawn; Ko, Il-Gyu; Kim, Sung-Eun; Sung, Yun-Hee; Kim, Bo-Kyun; Kim, Tae-Soo; Kim, Chang-Ju; Shin, Mal-Soon



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

PubMed Central

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.

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



Subcortical band heterotopia in rat offspring following maternal hypothyroxinaemia: structural and functional characteristics.  


Thyroid hormones (TH) play crucial roles in brain maturation and are important for neuronal migration and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported the presence of SBH in a rodent model of low level hypothyroidism induced by maternal exposure to the goitrogen, propylthiouracil (PTU). In the present study, we report the dose-response characteristics of this developmental malformation and the connectivity of heterotopic neurones with other brain regions, as well as their functionality. Pregnant rats were exposed to varying concentrations of PTU through the drinking water (0-10 p.p.m.) beginning on gestational day 6 to produce graded levels of TH insufficiency. Dose-dependent increases in the volume of the SBH present in the corpus callosum were documented in the adult offspring, with a clear presence at concentrations of PTU that resulted in minor (< 15%) reductions in maternal serum thyroxine as measured when pups were weaned. SBH contain neurones, oligodendrocytes, astrocytes and microglia. Monoaminergic and cholinergic processes were prevalent and many of the axons were myelinated. Anatomical connectivity of SBH neurones to cortical neurones and the synaptic functionality of these anatomical connections was verified by ex vivo field potential recordings. SBH persisted in adult offspring despite a return to euthyroid status on termination of exposure and these offspring displayed an increased sensitivity to seizures. Features of this model are attractive with respect to the investigation of the molecular mechanisms of cortical development, the effectiveness of therapeutic intervention in hypothyroxinaemia during pregnancy and the impact of the very modest TH imbalance that accompanies exposure to environmental contaminants. PMID:24889016

Gilbert, M E; Ramos, R L; McCloskey, D P; Goodman, J H



Stereological Evaluation of the Seminiferous Tubules of Rats after Maternal Undernutrition during the Lactation Period  

Microsoft Academic Search

The goal of this study is to evaluate, through stereological methods, some structural aspects of offspring testes whose dams were submitted to protein and energy-restricted diets during the lactation period. At birth, dams were separated into 3 groups: control group (C), receiving a diet with 23% protein; protein-restricted group (PR), receiving a diet with 8% protein; energy-restricted group (ER), receiving

Cristiane da Fonte Ramos; Alexandra Moreira da Silva; Waldemar Silva Costa; Francisco J. B. Sampaio



Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: Gender-dependent effects  

Microsoft Academic Search

Neonatal maternal separation (MS) has been used to model long-term changes in neurochemistry and behaviour associated with exposure to early-life stress. This study characterises changes in behavioural and neuroendocrine parameters following MS. On postnatal days (PND) 3–15, male and female Long–Evans rats underwent 3 h daily MS. Non-handled (NH) control offspring remained with the dams. Starting at PND 90, behaviour was

Helge A. Slotten; Mikhail Kalinichev; Jim J. Hagan; Charles A. Marsden; Kevin C. F. Fone



Maternal cocaine abuse resulting in necrotizing enterocolitis. An experimental study in a rat model. II. Results of perfusion studies  

Microsoft Academic Search

During the last decade, several publications have appeared associating the maternal use of cocaine and subsequent development\\u000a of necrotizing enterocolitis (NEC). In 1994, the effects of cocaine in pregnant rats had been reported by this group: a significant\\u000a decrease in the number of live births, mean birth weight and mean placental weight. In addition, histopathologic examinations\\u000a revealed severe inflammation and

Nizamettin Kilic; Cenk Büyükünal; Sergülen Dervisoglu; Tanju Yusuf Erdil; Enis Altiok



Chronic intake of caffeine during gestation down regulates metabotropic glutamate receptors in maternal and fetal rat heart  

Microsoft Academic Search

Summary.  Caffeine is the most widely consumed substance in the world which antagonizes adenosine effects. Adenosine acting through\\u000a A1 receptors inhibits glutamate release which binds to metabotropic glutamate receptors (mGluRs). Recently, we have shown that\\u000a maternal caffeine intake during gestation causes down-regulation of A1 and metabotropic glutamate receptors in the brain of both rat mothers and fetuses. In the present work

I. Iglesias; D. León; M. A. Ruiz; J. L. Albasanz; M. Martín



Analysis of hepatotoxicity in maternal and fetal rats after glucocorticoid administration by lipid histochemistry and thin layer chromatography  

Microsoft Academic Search

Changes in lipid metabolism of fetal and maternal rat livers were investigated on day 20 of pregnancy after administration of either 3 mg\\/kg or 24 mg\\/kg triamcinclone-acetonide or 124 mg\\/kg hydrocortisone in crystalline suspension to the mothers on day 15 of pregnancy. Sudan black B and Nile red as well as the UV-Schiff reaction and thin layer chromatography were used

H.-G. Frank; R. Gossrau; R. Graf



Effects of maternal and sibling deprivation on basal and stress induced hypothalamic-pituitary-adrenal components in the infant rat  

Microsoft Academic Search

Prolonged maternal deprivation during early infancy increases basal- and stress-induced corticosterone (CORT) levels, but the underlying mechanism is not clear. In general, stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, with secretion and compensatory synthesis of hypothalamic corticotropin-releasing hormone (CRH). In the infant rat, we have demonstrated that maximally tolerated acute cold stress induced a robust elevation of plasma CORT throughout the

Sarit Avishai-Eliner; Su-Jin Yi; Christopher J. L. Newth; Tallie Z. Baram



Impact of maternal chromium restriction on glucose tolerance, plasma insulin and oxidative stress in WNIN rat offspring.  


Robust evidence suggests that nutritional insult during fetal development could program the offspring to glucose intolerance, impaired insulin response and insulin resistance (IR). Considering the importance of chromium (Cr) in maintaining carbohydrate metabolism, this study determined the effect of maternal Cr restriction (CrR) on glucose metabolism and plasma insulin in Wistar/NIN (WNIN) rat offspring and the associated biochemical and/or molecular mechanisms. Female, weanling WNIN rats received ad libitum for 12 weeks, a control diet or the same with 65% restriction of Cr and mated with control males. Some of the Cr-restricted dams were rehabilitated from conception or parturition and their pups weaned on to control diet. At the time of weaning, half of the Cr restricted offspring were rehabilitated to control diet while others continued on Cr-restricted diet. Maternal CrR increased fasting plasma glucose, fasting insulin, homeostasis model assessment of IR, and area under the curve of glucose and insulin during oral glucose tolerance test in the offspring. Expression and activity of rate-limiting enzymes of glucose metabolism were comparable among different groups and expression of genes involved in insulin secretion was increased albeit in male offspring whereas antioxidant enzyme activities were decreased in offspring of both genders. Rehabilitation, in general, corrected the changes albeit partially. Maternal dietary CrR induced IR, impaired glucose tolerance in WNIN rat offspring and was associated with increased oxidative stress, which may predispose them to type 2 diabetes in their later life. PMID:21798994

Padmavathi, Inagadapa J N; Rao, Kalashikam Rajender; Raghunath, Manchala



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


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 Lévy et al. (2003) [Lévy, 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

Benetti, Fernando; Mello, Pâmela Billig; Bonini, Juliana Sartori; Monteiro, Siomara; Cammarota, Martín; Izquierdo, Iván



Growth retardation induced in rat fetuses by maternal fasting and massive doses of ergocalciferol.  


The present study was conducted in Wistar rat fetuses to investigate the growth retardation induced by maternal fasting and/or massive doses of ergocalciferol during the third trimester of pregnancy. Growth indices examined in 21-d fetuses were body weight and ossification of sacrococcygeal vertebrae, supraoccipital bone, sternebrae and proximal phalanges in the forepaw stained by alizarin red S. Growth retardation was expressed in hours by comparison with the normal standard development, or in sigma by calculating the relative difference from the control, utilizing the standard variance in normal fetuses. Degrees of growth retardation expressed in the common scales were different among the indices and between fasting and massive doses of ergocalciferol; body weight and ossification of sacrococcygeal vertebrae were most severely retarded by fasting and least by ergocalciferol. Ossification of sternebrae was moderately retarded by fasting and by ergocalciferol, and ossification of supraoccipital bone was moderately retarded by fasting but not by ergocalciferol. Ossification of proximal phalanges in the forepaw was least retarded by fasting and most severely retarded by ergocalciferol. The observed retardations were progressions relatable to the duration of fasting. Combined treatments of fasting and ergocalciferol showed more deleterious effects on growth than fasting only or ergocalciferol only and induced face anomalies, "carnival fetuses." These findings show that growth retardations induced by different nutritional disturbances may vary among indices and that comparisons of various indices are important in the analysis of teratological experiments. PMID:3494110

Ariyuki, F



Oxytocin-Dopamine Interactions Mediate Variations in Maternal Behavior in the Rat  

PubMed Central

Variations in maternal behavior among lactating rats associate with differences in estrogen-oxytocin interactions in the medial preoptic area (mPOA) and in dopamine levels in the nucleus accumbens (nAcc). Thus, stable, individual differences in pup licking/grooming (LG) are abolished by oxytocin receptor blockade or treatments that eliminate differences in the nAcc dopamine signal. We provide novel evidence for a direct effect of oxytocin at the level of the ventral tegmental area (VTA) in the regulation of nAcc dopamine levels. Mothers that exhibit consistently increased pup LG (i.e. high LG mothers) by comparison with low LG mothers show increased oxytocin expression in the mPOA and the paraventricular nucleus of the hypothalamus and increased projections of oxytocin-positive cells from both mPOA and paraventricular nucleus of the hypothalamus to the VTA. Direct infusion of oxytocin into the VTA increased the dopamine signal in the nAcc. Finally, high compared with low LG mothers show greater increases in dopamine signal in the nAcc during bouts of pup LG, and this difference is abolished with infusions of an oxytocin receptor antagonist directly into the VTA. These studies reveal a direct effect of oxytocin on dopamine release within the mesocorticolimbic dopamine system and are consistent with previous reports of oxytocin-dopamine interactions in the establishment and maintenance of social bonds.

Shahrokh, Dara K.; Zhang, Tie-Yuan; Diorio, Josie; Gratton, Alain; Meaney, Michael J.



Maternal tobacco smoke exposure during lactation inhibits catecholamine production by adrenal medullae in adult rat offspring.  


Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impact of tobacco exposure is still unknown. As postnatal nicotine exposure causes short- and long-term effects on pups' biochemistry and endocrine profiles, we have now evaluated some endocrine and metabolic parameters of the adult offspring whose mothers were tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C group, exposed to air, in the same conditions. Offspring were killed at 180-days-old. Body weight and food intake were evaluated. Blood, white adipose tissue, adrenal, and liver were collected. All significant data were p<0.05. The adult SE offspring showed no change in body weight, cumulative food intake, serum hormone profile, serum lipid profile, or triglycerides content in liver. However, in adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal alterations during lactation, tobacco smoke exposure through breast milk only programmed the adrenal medullary function at adulthood and this dysfunction can have consequence on stress response. Thus, an environment free of smoke during lactation period is essential to improve health outcomes in adult offspring. PMID:22618271

Santos-Silva, A P; Lisboa, P C; Pinheiro, C R; Maia, L A; Peixoto-Silva, N; Abreu-Villaça, Y; Moura, E G; Oliveira, E



Maternal consumption of Lactobacillus plantarum 299v affects gastrointestinal growth and function in the suckling rat.  


After birth, the gastrointestinal (GI) tract undergoes vast structural and functional adaptations to be able to digest mother's milk and later, during the weaning period, solid food. Studies on germ-free animals have shown the role of the gut microbiota for stimulating GI maturation, but which groups are involved is unclear. In the present study, we administered the probiotic bacterium, Lactobacillus plantarum 299v (Lp299v), in the drinking water to pregnant and lactating rat dams until their pups had reached an age of 14 d. It was found that Lp299v colonizing the mothers were also able to colonize the pups, which had an impact on their gut growth and function. The small intestine, pancreas and liver weighed more in the 14 d-old pups born from dams exposed to Lp299v than in the control pups from dams given only water. Furthermore, the Lp299v pups showed decreased gut permeability. Despite a heavier spleen in the Lp299v pups, as compared to the control pups, no significant increase in the acute-phase protein, haptoglobin, was found. In conclusion, the results reported here clearly show that manipulating the maternal microflora by exposing expecting mothers to a Gram-positive, probiotic bacterium prior to parturition and during lactation impacts the gut growth and function in the offspring. PMID:18179726

Fåk, Frida; Ahrné, Siv; Molin, Göran; Jeppsson, Bengt; Weström, Björn



Short- and long-term reproductive effects of prenatal and lactational growth restriction caused by maternal diabetes in male rats  

PubMed Central

Background A suboptimal intrauterine environment may have a detrimental effect on gonadal development and thereby increases the risk for reproductive disorders and infertility in adult life. Here, we used uncontrolled maternal diabetes as a model to provoke pre- and perinatal growth restriction and evaluate the sexual development of rat male offspring. Methods Maternal diabetes was induced in the dams through administration of a single i.v. dose of 40 mg/kg streptozotocin, 7 days before mating. Female rats presenting glycemic levels above 200 mg/dL after the induction were selected for the experiment. The male offspring was analyzed at different phases of sexual development, i.e., peripuberty, postpuberty and adulthood. Results Body weight and blood glucose levels of pups, on the third postnatal day, were lower in the offspring of diabetic dams compared to controls. Maternal diabetes also provoked delayed testicular descent and preputial separation. In the offspring of diabetic dams the weight of reproductive organs at 40, 60 and 90 days-old was lower, as well as sperm reserves and sperm transit time through the epididymis. However the plasma testosterone levels were not different among experimental groups. Conclusions It is difficult to isolate the effects directly from diabetes and those from IUGR. Although the exposure to hyperglycemic environment during prenatal life and lactation delayed the onset of puberty in male rats, the IUGR, in the studied model, did not influenced the structural organization of the male gonads of the offspring at any point during sexual development. However the decrease in sperm reserves in epididymal cauda and the acceleration in sperm transit time in this portion of epididymis may lead to an impairment of sperm quality and fertility potential in these animals. Additional studies are needed in attempt to investigate the fertility of animals with intrauterine growth restriction by maternal diabetes and possible multigenerational effects.



Enhancement of neonatal rat ductal responsiveness to prostaglandin E2 after maternal treatment with enalapril or captopril.  


This work was conducted to determine whether the angiotensin-converting enzyme inhibitors (ACEIs) (enalapril and captopril) administered to mother rats prenatally can potentiate a re-opening of the neonatal ductus arteriosus (DA) induced by prostaglandin E2 (PGE2) after postnatal closure. A subcutaneous injection of PGE2 (4 micrograms) was administered to newborn rats 3 hr after a Cesarean delivery from females which had been orally given 0.1, 1 or 10 mg/kg/day of enalapril or 15 or 150 mg/kg/day of captopril from day 14 to day 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in the newborn rats of mothers who were transplacentally administered these agents compared to the controls, except at the low dose (0.1 mg/kg) group of enalapril. We found that the level in the neonatal lungs of 15-hydroxy prostaglandin dehydrogenase, a key enzyme that catalyzes PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected after maternal treatment with enalapril or captopril. These results indicate that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal ACEI treatment, but the catabolism of PGE2 in the lungs did not contribute to this response. PMID:9764418

Togashi, H; Takizawa, T; Kawahata, M; Yamamoto, M; Arishima, K; Masaoka, T



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

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.

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



Protein restoration in low-birth-weight rat offspring derived from maternal low-protein diet leads to elevated hepatic CYP3A and CYP2C11 activity in adulthood.  


The World Health Organization has identified hypercholesterolemia to be one of the major symptoms encompassing the metabolic syndrome. Moreover, epidemiologic evidence indicates that low-birth-weight offspring are at greater risk of developing the metabolic syndrome. Previous work in our laboratory demonstrated that maternal protein restriction (MPR) results in impaired fetal growth and hypercholesterolemia in adulthood. This was attributed to repression of hepatic CYP7A1, a rate-limiting enzyme that catabolizes cholesterol to bile acids. Another important function of hepatic cytochrome P450 enzymes is the phase I oxidative metabolism of drugs (i.e., statins for hypercholesterolemia), which can significantly impact pharmacokinetics. We hypothesized that MPR offspring may have altered ability to metabolize drugs in adulthood. To address this hypothesis, we maintained Wistar rats on a 20% protein diet (control) or a low 8% protein diet throughout prenatal and postnatal life (LP1) or exclusively during prenatal life and weaning (LP2). Intriguingly CYP3A and CYP2C11 intrinsic clearance (Vmax/Km) was significantly increased exclusively in LP2 offspring at postnatal day 130 compared with control or LP1 offspring, as evaluated by testosterone enzyme kinetics in liver microsomes. The increase in activity was secondary to an increase in CYP3A23 and CYP2C11 mRNA. Collectively, these findings suggest that a low-birth-weight offspring with postnatal catch-up growth may have a diminished response to xenobiotics metabolized by CYP3A and CYP2C11 enzymes. PMID:24212381

Sohi, Gurjeev; Barry, Eric J; Velenosi, Thomas J; Urquhart, Bradley L; Hardy, Daniel B



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


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

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




PubMed Central

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 21) 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-? protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-? protein levels in the lobules and terminal end buds (TEBs). Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the TEBs, lobules or ducts. 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 7-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-? content was causally linked to increased mammary cancer risk among the offspring.

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



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

PubMed Central

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.

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



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

SciTech Connect

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.

Ronco, Ana Maria, E-mail: [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Saez, Daniel [Faculty of Veterinary Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Hirsch, Sandra [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Zepeda, Ramiro [Faculty of Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Llanos, Miguel N. [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile)



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


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

Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J



Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring.  


The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults. PMID:24374911

Lim, Wei Ling; Soga, Tomoko; Parhar, Ishwar S



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


Repeated brief maternal separation (i.e. 15 min 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 1 week, FG-injected rats and surgically intact littermates were exposed to either a 15-min restraint stress or an unrestrained control condition, and then perfused 1 h 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

Banihashemi, L; O'Neill, E J; Rinaman, L



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

PubMed Central

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.

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



Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development, and behavior in the rat  

Microsoft Academic Search

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride\\u000a (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without\\u000a altering maternal gestational parameters and\\/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20\\u000a mg\\/kg) and high-dose N (5.0 mg\\/kg) on gestation

Sonya K. Sobrian; S. F. Ali; W. Slikker; R. Robert Holson



Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood  

Microsoft Academic Search

Rationale  Adverse events during early developmental stages can induce persistent changes in central stress circuits, leading to increased\\u000a stress sensitivity in adulthood, as is apparent in the maternally separated (MS) rat model. It is widely accepted that the\\u000a stress peptide corticotropin-releasing factor (CRF) by binding to CRF1 and 2 receptors (CRFR1 and CRFR2) is key to these phenotypic\\u000a changes.\\u000a \\u000a \\u000a \\u000a \\u000a Objectives  These studies

Dervla O’Malley; Timothy G. Dinan; John F. Cryan



Measurement of somatomedin-related peptides in fetal, neonatal, and maternal rat serum by insulin-like growth factor (IGF) I radioimmunoassay, IGF-II radioreceptor assay (RRA)  

SciTech Connect

Previous measurements of somatomedins (Sms) and insulin-like growth factors (IGFs) in maternal and fetal serum have yielded contradictory results. We have, therefore, measured maternal, fetal, and neonatal rat serum with two highly specific assays: 1) IGF-I/Sm-C RIA and 2) a highly specific IGF-II/rat placental membrane radioreceptor assay (RRA). In addition, we have made measurements with a less specific multiplication-stimulating activity (MSA)-rat placental membrane RRA. To avoid possible serious artifacts created by Sm-binding proteins, preliminary acid-ethanol extraction of serum was performed. Results are expressed in terms of a reference human serum with an assigned potency of 1 U/ml. We now conclude that radioimmunoassayable IGF-I is present in higher concentrations than previously reported interm fetal rat serum and that radioreceptor assayable IGF-II is selectively elevated in rat fatal and neonatal life and may have unique metabolic and rowth-promoting significance.

Daughaday, W.H.; Parker, K.A.; Borowsky, S.; Trivedi, B.; Kapadia, M.



Corticosterone administration to rat pups, but not maternal separation, affects sexual maturation and glucocorticoid receptor immunoreactivity in the testis.  


Prenatal stress strongly affects sexual dimorphism of male rats. Much less information is instead available on the effects of postnatal stress on sexual maturation during the so-called stress hyporesponsive period (SHRP). For this reason, we compared corticosterone-treated (CS; 10 mg/kg sc, suspended in sesame oil) or maternally separated pups (MS; 5 h/day in the first week of life) with control rats. Control and MS pups also received sesame oil injections. The effects of these procedures on physical development (body weight and eye opening), sexual maturation [anogenital distance, testis weight, 3beta-hydroxysteroid dehydrogenase/(Delta5-4) (3betaHSD) isomerase activity and time to testis descent] and glucocorticoid receptor (GR) immunoreactivity in the testis were examined. Corticosterone treatment significantly (P<.05) advanced testis descent and increased testis weight and 3betaHSD activity at puberty. In addition, adult CS rats presented higher levels of GR immunoreactivity in testicular tubules when compared to control and MS rats. No differences were found between control and MS rats. On this basis, we propose that the silencing of adrenocortical function during the SHRP could be finalized to preserve sexual maturation from the influence of glucocorticoid effects. As SHRP is unique to rodents, this phenomenon could be related to their successful reproductive strategy. PMID:12076728

Biagini, Giuseppe; Pich, Emilio Merlo



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


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

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



Maternal dexamethasone exposure inhibits the gonadotropin-releasing hormone neuronal movement in the preoptic area of rat offspring.  


Migration and final positioning of gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA) is critical for reproduction. It is known that maternal dexamethasone (DEX) exposure impairs reproductive function and behaviour in the offspring. However, it is still not known whether maternal DEX exposure affects the postnatal GnRH neurons in the offspring. This study determined the neuronal movement of enhanced green fluorescent protein (EGFP)-tagged GnRH neurons in slice culture of postnatal day 0 (P0), P5 and P50-60 transgenic male rats. Effect of maternal DEX treatment on EGFP-GnRH neuronal movement and F-actin distribution on GnRH neurons at P0 stage were studied. Time-lapse analysis of P0 and P5 EGFP-GnRH neurons displayed active cellular movement within the POA compared to young adult P50-60 stages, suggesting possible fine-tuning movement for positioning of early postnatal GnRH neurons. The DEX-treated EGFP-GnRH neurons demonstrated decreased motility in the POA and reduced F-actin distribution in the GnRH neurons at 60 h culture compared to the vehicle-treated. These results suggest that the P0 GnRH neuronal movement in the POA is altered by maternal DEX exposure, which possibly disrupts the fine-tuning process for positioning and development of early postnatal GnRH neurons in the brain, potentially linked to reproductive dysfunction in adulthood. © 2014 S. Karger AG, Basel. PMID:24713635

Lim, Wei Ling; Soga, Tomoko; Parhar, Ishwar S



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

SciTech Connect

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.

Leichter, J. (Univ. of British Columbia, Vancouver (Canada))



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

PubMed Central

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.

Kojima, Sayuri; Alberts, Jeffrey R.



Maternal exposure to low levels of corticosterone during lactation increases social play behavior in rat adolescent offspring.  


Although costly in energy and time, social play is present and evolutionarily conserved in nearly all young mammals. Ontogenetic factors responsible for this particular form of supposed rewarding behavior are incompletely understood. Here, we have focused our attention on maternal glucocorticoid hormone. We used a model in which neonate rats are fed by mothers in which drinking water has been supplemented with 0.2 mg/ml corticosterone. The control groups were lactated by water-drinking mothers. Both male and female adolescent offspring of corticosterone (CORT) supplemented dams (CORT-nursed) showed an increase in social play behavior (i.e., pinning, pouncing, wrestling/boxing and social exploration) when compared to controls. No differences were observed between CORT-nursed progeny of both sexes and controls in the exploration of the arena during the social encounter. Finally, no differences were found in CORT plasma levels in basal conditions and following a social play session in both male and female CORT-nursed rats. These results indicate that variations in the maternal glucocorticoid status are able, directly or indirectly, to influence social play behavior in the offspring, although there is no direct relationship between the level of social play behavior and the intensity of adrenocortical activation. PMID:23159867

Cinque, Carlo; Zuena, Anna Rita; Catalani, Assia; Giuli, Chiara; Tramutola, Antonella; Scaccianoce, Sergio



Treatment with a Monoclonal Antibody against Methamphetamine and Amphetamine Reduces Maternal and Fetal Rat Brain Concentrations in Late Pregnancy.  


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

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



Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction  

PubMed Central

We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.



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


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

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



Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups.  


Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to beta-lactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+) regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII, and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4(+) Foxp3(+) cells (P < 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response. PMID:19759244

Tooley, Katie L; El-Merhibi, Adaweyah; Cummins, Adrian G; Grose, Randall H; Lymn, Kerry A; DeNichilo, Mark; Penttila, Irmeli A



The feto-placental glucose steal phenomenon is a major cause of maternal metabolic adaptation during late pregnancy in the rat  

Microsoft Academic Search

Summary  The aim of this study was to determine the extent to which a feto-placental glucose steal phenomenon contributes to the process of maternal metabolic adaptation to late pregnancy. Glucose metabolism was studied in virgin control, pregnant rats and virgin rats with a phlorizin-induced model of the feto-placental glucose steal phenomenon. Whole body glucose kinetics and glucose uptake into individual tissues

C. J. Nolan; J. Proietto



Maternal separation increases GABA(A) receptor-mediated modulation of norepinephrine release in the hippocampus of a rat model of ADHD, the spontaneously hypertensive rat.  


Experiencing early life stress increases the risk of developing a psychiatric disorder later in life, possibly by altering neural networks, such as the locus-coeruleus norepinephrine (LC-NE) system. Whether early life stress affects the LC-NE system directly, or whether the effects are via changes in glutamate and GABA modulation of the LC-NE system, is unclear. Early life stress has been shown to alter glutamate and GABA transmission, and in particular, to alter GABA(A) receptor expression. The LC-NE system has been implicated in attention-deficit/hyperactivity disorder (ADHD), amongst other disorders, and is over-responsive to glutamate stimulation in a validated rat model of ADHD, the spontaneously hypertensive rat (SHR). It is plausible that the LC-NE system, or glutamate and GABA modulation thereof, in an individual already genetically predisposed to develop ADHD, or in SHR, may respond in a unique way to early life stress. To investigate this we applied a mild developmental stressor, maternal separation, onto SHR, and onto their control strain, Wistar-Kyoto rats (WKY), from post-natal day (P)2-14. On P50-52, in early adulthood, we assayed glutamate and potassium stimulated release of radio-actively labelled NE ((3)[H]NE) from hippocampal slices using an in vitro superfusion technique, in the presence or absence of a GABA(A) receptor antagonist, bicuculline. Our results show that maternal separation altered GABA(A) receptor-mediated modulation of NE release in the hippocampus of the two strains in opposite directions, increasing it in SHR and decreasing it in WKY. Our findings indicate that effects of early life stress are highly dependent on genetic predisposition, since opposite changes in GABA(A) receptor-mediated modulation of NE release were observed in the rat model of ADHD, SHR, and their control strain, WKY. PMID:23276497

Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A



Maternal Undernutrition during Late Gestation Induces Fetal Overexposure to Glucocorticoids and Intrauterine Growth Retardation, and Disturbs the Hypothalamo-Pituitary Adrenal Axis in the Newborn Rat  

Microsoft Academic Search

As fetal overexposure to glucocorticoids has been postulated to induce intrauterine growth retardation (IUGR) in humans, we in- vestigated the effects of maternal 50% food restriction (FR50) in rats during the last week of gestation on the hypothalamo-pituitary ad- renal (HPA) axis activity in both mothers and their fetuses. In moth- ers, FR50 increased both the plasma corticosterone (B) level




Adherence to protein restriction in patients with type 2 diabetes mellitus: a randomized trial  

Microsoft Academic Search

Objective: To describe the extent to which diet counselling can decrease protein intake, and to identify predictors of adherence.Design: (1) Randomized trial; (2) observational longitudinal study.Subjects: (1) 125 type 2 diabetic patients in primary care; (2) 59 patients in the experimental group.Intervention: For a period of 12 months, dieticians provided guidance on protein restriction (experimental group, n=59) or the usual

LTJ Pijls; H de Vries; JThM van Eijk; A. J. M. Donker



Long-term effects of maternal separation on ethanol intake and brain opioid and dopamine receptors in male Wistar rats.  


Accumulating evidence indicates that an animal's response to a drug can be profoundly affected by early environmental influences. The brain opioid and dopamine systems may play a critical role in these effects, since various types of stress and drugs of abuse promote alterations in these brain systems. To study this further, we investigated long-term behavioural and neurochemical effects of repeated maternal separation in male Wistar rats. The pups were separated in litters daily from their dams for either 15 min (MS15) or 360 min (MS360) from postnatal days 1-21. Analysis of the kappa- and delta-opioid, dopamine D(1)- and D(2)-like receptors with receptor autoradiography revealed long-term neurochemical changes in several brain areas. D(1)-like receptor binding was affected in the hippocampus and D(2)-like receptor binding in the ventral tegmental area and the periaqueductal gray, whereas minor changes were seen in opioid receptor density after maternal separation. At 10-13 weeks of age, MS15 rats had a lower ethanol intake whereas, the MS360 rats consumed more 8% ethanol solution compared with MS15 and animal facility-reared rats. Ethanol consumption altered kappa-receptor density in several brain areas, for example the amygdala, substantia nigra and the periaqueductal gray. D(1)-like receptor binding was affected in distinct brain areas, including the nucleus accumbens, where also delta-opioid receptor density was changed in addition to the frontal cortex. Ethanol-induced changes were observed in D(2)-like receptor density in the ventral tegmental area in MS360, and in the ventral tegmental area and frontal-parietal cortex in animal facility-reared rats. These findings show that early experiences can induce long-lasting changes in especially brain dopamine receptor density and that ethanol consumption induces alterations in opioid and dopamine receptor density in distinct brain areas. It is also suggested that changes induced by repeated MS15 may provide protection against high voluntary ethanol intake. PMID:14568037

Ploj, K; Roman, E; Nylander, I



Maternal Perinatal Undernutrition Alters Postnatal Development of Chromaffin Cells in the Male Rat Adrenal Medulla  

Microsoft Academic Search

Numerous data suggest that the development of the sympathoadrenal system is highly sensitive to the perinatal environment. We previously reported that maternal perinatal food restriction by 50% (FR50) altered chromaffin cell (CC) organization and activity in offspring at weaning. This study investigated the effects of FR50 on the postnatal time course of CC functional and structural adaptations. FR50 pups exhibited

Olivier Molendi-Coste; Christine Laborie; Maria Cristina Scarpa; Valérie Montel; Didier Vieau; Christophe Breton




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...



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...


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

PubMed Central

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.

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



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


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

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



A Maternal "Junk Food" Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring  

PubMed Central

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

Bayol, Stephanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.



A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.  


With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C



Pre-Weaning Growth Hormone Treatment Ameliorates Bone Marrow Macrophage Inflammation in Adult Male Rat Offspring following Maternal Undernutrition  

PubMed Central

Maternal undernutrition (UN) is associated with the development of obesity and metabolic complications in adult offspring. While the role of inflammation in obesity and related comorbidities has been well established, there is little evidence regarding the effects of maternal UN-induced programming on immune function in male adult offspring. This study examines the effects growth hormone (GH), which is known to induce anti-inflammatory effects, on maternal UN-induced bone marrow macrophage (BMM) function in adult male offspring. Sprague-Dawley rats were assigned to chow (C) or UN (50% ad libitum; UN) diet throughout gestation. Male C and UN pups received saline (CS/UNS) or GH (2.5 µg/g/d; CGH/UNGH) from day 3–21. Bone marrow hematopoietic cells were differentiated to a macrophage phenotype in the presence of M-CSF (50 ng/ml). Differentiated bone marrow macrophages (BMM) were stimulated with LPS (100 ng/ml) for 6 h. UNS-derived BMM had significantly increased secretion and expression of IL-1? and IL-6 following LPS stimulation. This was accompanied by increased expression of IL-1R1, IL-6R and TLR4. Pre-weaning GH treatment reversed this pro-inflammatory phenotype. Furthermore UNGH displayed increased expression of markers of alternative (M2) macrophage activation, mannose receptor and PPAR?. This study demonstrates that fetal UN exposure primes hematopoietic immune cells to a more potent pro-inflammatory phenotype with heightened cytokine secretion and receptor expression. Furthermore these cells are pre-disposed to pro-inflammatory M1 macrophage phenotype which has wide-reaching and important effects in terms of obesity and metabolic disease.

Reynolds, Clare M.; Li, Minglan; Gray, Clint; Vickers, Mark H.



Gestational protein restriction impairs insulin-regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring.  


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 diet-exposed 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 diet-fed 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

Blesson, Chellakkan S; Sathishkumar, Kunju; Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar



Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus.  


Insulin-like growth factor 2 (Igf2) regulates development, memory and adult neurogenesis in the hippocampus. Calorie restriction (CR) is known to modulate non-neuronal Igf2 expression intergenerationally, but its effect has not been evaluated on brain Igf2. Here, Sprague-Dawley (S) dams underwent moderate CR between gestational days 8-21. To identify parent of origin expression pattern of the imprinted Igf2 gene, their offspring (SS F1) were mated with naïve male or female Brown Norway (B) rats to obtain the second generation (BS and SB F2) progeny. CR did not affect adult hippocampal Igf2 transcript levels in SS F1 males or their BS F2 progeny, but increased it in SS F1 females and their SB F2 offspring. The preferentially maternal Igf2 expression in the SB F2 control male hippocampus relaxed to biallelic with CR, with no effect of grandmaternal diet in any other groups. Thus, allele-specific and total expression of hippocampal Igf2 is affected by maternal, grandmaternal CR in a strain and sex-specific manner. PMID:24845189

Harper, Kathryn M; Tunc-Ozcan, Elif; Graf, Evan N; Herzing, Laura B K; Redei, Eva E



Hypoactivation of CRF Receptors, Predominantly Type 2, in the Medial-Posterior BNST Is Vital for Adequate Maternal Behavior in Lactating Rats  

PubMed Central

Maternal behavior ensures the proper development of the offspring. In lactating mammals, maternal behavior is impaired by stress, the physiological consequence of central corticotropin-releasing factor receptor (CRF-R) activation. However, which CRF-R subtype in which specific brain area(s) mediates this effect is unknown. Here we confirmed that an intracerebroventricularly injected nonselective CRF-R antagonist enhances, whereas an agonist impairs, maternal care. The agonist also prolonged the stress-induced decrease in nursing, reduced maternal aggression and increased anxiety-related behavior. Focusing on the bed nucleus of the stria terminalis (BNST), CRF-R1 and CRF-R2 mRNA expression did not differ in virgin versus lactating rats. However, CRF-R2 mRNA was more abundant in the posterior than in the medial BNST. Pharmacological manipulations within the medial-posterior BNST showed that both CRF-R1 and CRF-R2 agonists reduced arched back nursing (ABN) rapidly and after a delay, respectively. After stress, both antagonists prevented the stress-induced decrease in nursing, with the CRF-R2 antagonist actually increasing ABN. During the maternal defense test, maternal aggression was abolished by the CRF-R2, but not the CRF-R1, agonist. Anxiety-related behavior was increased by the CRF-R1 agonist and reduced by both antagonists. Both antagonists were also effective in virgin females but not in males, revealing a sexual dimorphism in the regulation of anxiety within the medial-posterior BNST. In conclusion, the detrimental effects of increased CRF-R activation on maternal behavior are mediated via CRF-R2 and, to a lesser extent, via CRF-R1 in the medial-posterior BNST in lactating rats. Moreover, both CRF-R1 and CRF-R2 regulate anxiety in females independently of their reproductive status.

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



Hypoactivation of CRF Receptors, Predominantly Type 2, in the Medial-Posterior BNST Is Vital for Adequate Maternal Behavior in Lactating Rats.  


Maternal behavior ensures the proper development of the offspring. In lactating mammals, maternal behavior is impaired by stress, the physiological consequence of central corticotropin-releasing factor receptor (CRF-R) activation. However, which CRF-R subtype in which specific brain area(s) mediates this effect is unknown. Here we confirmed that an intracerebroventricularly injected nonselective CRF-R antagonist enhances, whereas an agonist impairs, maternal care. The agonist also prolonged the stress-induced decrease in nursing, reduced maternal aggression and increased anxiety-related behavior. Focusing on the bed nucleus of the stria terminalis (BNST), CRF-R1 and CRF-R2 mRNA expression did not differ in virgin versus lactating rats. However, CRF-R2 mRNA was more abundant in the posterior than in the medial BNST. Pharmacological manipulations within the medial-posterior BNST showed that both CRF-R1 and CRF-R2 agonists reduced arched back nursing (ABN) rapidly and after a delay, respectively. After stress, both antagonists prevented the stress-induced decrease in nursing, with the CRF-R2 antagonist actually increasing ABN. During the maternal defense test, maternal aggression was abolished by the CRF-R2, but not the CRF-R1, agonist. Anxiety-related behavior was increased by the CRF-R1 agonist and reduced by both antagonists. Both antagonists were also effective in virgin females but not in males, revealing a sexual dimorphism in the regulation of anxiety within the medial-posterior BNST. In conclusion, the detrimental effects of increased CRF-R activation on maternal behavior are mediated via CRF-R2 and, to a lesser extent, via CRF-R1 in the medial-posterior BNST in lactating rats. Moreover, both CRF-R1 and CRF-R2 regulate anxiety in females independently of their reproductive status. PMID:25031406

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



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

PubMed Central

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.

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



Maternal and early life arsenite exposure impairs neurodevelopment and increases the expression of PSA-NCAM in hippocampus of rat offspring.  


Although epidemiological investigations indicate that chronic arsenic exposure can induce developmental neurotoxicity in children, the molecular mechanisms are still poorly understood. Neural cell adhesion molecules (NCAMs) play critical roles during the development of nervous system. Polysialylation of NCAM (PSA-NCAM) is a critical functional feature of NCAM-mediated cell interactions and functions. The present study aimed at investigating the effects of maternal and early life arsenite exposure on NCAM and PSA-NCAM in rat offspring. To this end, mother rats were divided into three groups and exposed to 0, 2.72 and 13.6mg/L sodium arsenite, respectively, during gestation and lactation. After weaning, rat offspring drank the same solution as their mothers. Neural reflex parameters, arsenic level of hippocampus, ultra-structural changes of hippocampus, the expression of NCAM, PSA-NCAM and two polysialyltransferases (STX and PST) in rat offspring were assessed. Arsenite exposure significantly prolonged the time of completing reflex response of surface righting, negative geotaxis and cliff avoidance of rat offspring in 13.6mg/L As-exposed group. Neurons and capillaries presented pathological changes and the expression of NCAM, PSA-NCAM, STX and PST were up-regulated in hippocampus of rat offspring exposed to arsenite. These results indicated that maternal arsenite exposure increases the expression of PSA-NCAM, NCAM and polysialyltransferases in hippocampus of rat offspring on postnatal day (PND) 21 and PND120, which might contribute to the impaired neurodevelopment following arsenite exposure. PMID:23811142

Luo, Jiaohua; Qiu, Zhiqun; Chen, Ji'an; Zhang, Liang; Liu, Wenyi; Tan, Yao; Shu, Weiqun



Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats.  


Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS. PMID:23139220

Hu, Shufen; Xiao, Ying; Zhu, Liyan; Li, Lin; Hu, Chuang-Ying; Jiang, Xinghong; Xu, Guang-Yin



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

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 (0.25–2.0 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 (0.25–2.0 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 mother–infant relationship.

Farrar, Andrew M.; Hockemeyer, Jorg; Muller, Christa E.; Salamone, John D.; Morrell, Joan I.



Brain-blood amino acid correlates following protein restriction in murine maple syrup urine disease  

PubMed Central

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 ?M, 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.



Differential activation of the prefrontal cortex and amygdala following psychological stress and colorectal distension in the maternally separated rat.  


Visceral hypersensitivity is a hallmark of many clinical conditions and remains an ongoing medical challenge. Although the central neural mechanisms that regulate visceral hypersensitivity are incompletely understood, it has been suggested that stress and anxiety often act as initiating or exacerbating factors. Dysfunctional corticolimbic structures have been implicated in disorders of visceral hypersensitivity such as irritable bowel syndrome (IBS). Moreover, the pattern of altered physiological responses to psychological and visceral stressors reported in IBS patients is also observed in the maternally separated (MS) rat model of IBS. However, the relative contribution of various divisions within the cortex to the altered stress responsivity of MS rats remains unknown. The aim of this study was to analyze the cellular activation pattern of the prefrontal cortex and amygdala in response to an acute psychological stressor (open field) and colorectal distension (CRD) using c-fos immunohistochemistry. Several corticoamygdalar structures were analyzed for the presence of c-fos-positive immunoreactivity including the prelimbic cortex, infralimbic cortex, the anterior cingulate cortex (both rostral and caudal) and the amygdala. Our data demonstrate distinct activation patterns within these corticoamygdalar regions including differential activation in basolateral versus central amygdala following exposure to CRD but not the open field stress. The identification of this neuronal activation pattern may provide further insight into the neurochemical pathways through which therapeutic strategies for IBS could be derived. PMID:24513388

Felice, V D; Gibney, S M; Gosselin, R D; Dinan, T G; O'Mahony, S M; Cryan, J F



Effects of maternal 4-tert-octylphenol exposure on the reproductive tract of male rats at adulthood.  


Increases in human male reproductive disorders (testicular cancer, cryptorchidism, hypospadias, and low sperm counts) might stem from increased exposure of the developing male to environmental estrogens. In the present study, we investigated the effects of octylphenol (OP), an estrogenic compound, exposure on the male reproductive system during the fetal period in which the development of reproductive organs and sexual differentiation occurs. Male rats were treated with OP in utero at doses of control (vehicle), 100 or 250 mg/kg/day. After birth, male rats were allowed to grow until adulthood, and then testes, epididymides, and prostate glands were investigated histopathologically. Sperm counts and percentage of abnormal sperm were determined. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. Treatment with OP caused abnormalities in the histology of the testis and epididymis and induced atrophy of prostate glands tubules. Although there were no differences in sperm counts among treatment groups, abnormal sperm percentages in the high dose group increased significantly. The results of this study demonstrate that maternally injected OP causes adverse effects on male reproductive tract at adulthood, especially on sperm structure. PMID:16520019

Aydo?an, Müfide; Barlas, Nurhayat




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...


Developmental timing of the effects of maternal care on gene expression and epigenetic regulation of hormone receptor levels in female rats.  


Maternal care experienced during postnatal development has enduring effects on neuroendocrine function and behavior. Previous studies in rats have illustrated the effect of maternal licking/grooming (LG) on hormone receptors and maternal behavior of adult female offspring associated with altered DNA methylation. However, the developmental timing of these effects, which provide insight into the cellular and molecular pathways through which early experience alters later behavior, had not been explored. Here, we demonstrate the developmental emergence of these outcomes and use cross-fostering to identify sensitive periods for these effects. Estrogen receptor (ER)? and ER? mRNA levels within the medial preoptic area (MPOA) of the hypothalamus were increased by postnatal day (PN)21 in female offspring of high LG dams; LG-associated increases in oxytocin receptor mRNA levels were observed beyond the weaning period. Quantification of ER?-immunoreactivity indicated a high degree of neuroanatomical specificity of LG effects within the MPOA that were observed by PN6. Reduced DNA methylation and histone 3 lysine 9 tri-methylation and increased histone 3 lysine 4 tri-methylation at the ER? gene promoter (Esr1) were detected at PN21 in high LG female offspring. Latency to engage in maternal behavior toward donor pups was significantly shorter among high LG females. Cross-fostering revealed that maternal sensitization and MPOA ER? levels are sensitive to maternal care experienced before but not after PN10. Differential windows of plasticity were identified for ER? and oxytocin receptor mRNA levels. These studies contribute significantly to our understanding of the molecular, neurobiological, and behavioral pathways through which variation in maternal behavior is transmitted from one generation to the next. PMID:24002038

Peña, Catherine Jensen; Neugut, Y Dana; Champagne, Frances A



Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation  

PubMed Central

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.

Lee, Jong-Ho; Kim, Jin Young



Expression of c- fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats  

Microsoft Academic Search

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while

Michael Numan; Marilyn J Numan; Sandra R Marzella; Andrea Palumbo



Effect of Maternal Lipopolysaccharide Administration on the Development of Dopaminergic Receptors and Transporter in the Rat Offspring  

PubMed Central

Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS) model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA) system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R) and dopamine transporter (DAT) binding levels were measured in the prefrontal cortex (PFC) and sub cortical regions (dorsal striatum and nucleus accumbens core and shell) at pre pubertal (P35) and post pubertal ages (P60). We found a significant decrease in D2R ligand [3H] YM-90151-2 binding in the medial PFC (mPFC) in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [3H] SCH23390 binding to D1R. However, the level of [125I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL) part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV)-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection animal models as well as schizophrenia.

Baharnoori, Moogeh; Bhardwaj, Sanjeev K.; Srivastava, Lalit K.



Litter Gender Composition and Sex Affect Maternal Behavior and DNA Methylation Levels of the Oprm1 Gene in Rat Offspring  

PubMed Central

The mu-opioid receptor is encoded by the Oprm1 gene and contributes to mother–infant behaviors. Rodent dams lick male pups more than female pups in the anogenital region. This behavior is linked to stress responsivity in the offspring that may be mediated by epigenetic changes. We hypothesized that maternal behavior may affect DNA methylation levels of the Oprm1 gene and show sex differences. To further explore sex differences in mother–pup behaviors and DNA methylation levels, we altered the litter gender composition (LGC) of rats. Litters were culled to eight all male, all female, or four male/four female pups on postnatal (PN) day 1. On PN4, 7, and 10, a dam was placed in a test cage with a pup for a 10-min period. Latency to pup contact was determined as were times spent licking the anogenital and other body regions of the pup. Frequencies of other behaviors were tabulated. On PN35, samples from various brain regions were obtained. DNA methylation at specific CpG sites in the Oprm1 promoter region were measured by direct sequencing of bisulfite-treated DNA. LGC and sex interacted with day for latency to pup contact. Latencies were longest on PN4 for single-sex males and on PN10 for single-sex females. Dams licked male pups more than female pups in both the anogenital and other body areas. Sex differences were seen in other behaviors. LGC altered DNA methylation at specific CpG's of Oprm1 in hippocampus with higher levels in single-sex rats. In nucleus accumbens, single-sex males showed hypermethylation levels, a trend seen in caudate–putamen. Results confirm and extend sex differences in maternal care with modest LGC effects. That both LGC and sex have enduring effects on DNA methylation of the Oprm1 gene in brain regions associated with addiction, stress regulation, motivation, and cognition may suggest one factor that contributes to gender differences in these behaviors.

Hao, Yanli; Huang, Wen; Nielsen, David A.; Kosten, Therese A.



Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.  


Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS) model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA) system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R) and dopamine transporter (DAT) binding levels were measured in the prefrontal cortex (PFC) and sub cortical regions (dorsal striatum and nucleus accumbens core and shell) at pre pubertal (P35) and post pubertal ages (P60). We found a significant decrease in D2R ligand [(3)H] YM-90151-2 binding in the medial PFC (mPFC) in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [(3)H] SCH23390 binding to D1R. However, the level of [(125)I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL) part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV)-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection animal models as well as schizophrenia. PMID:23349891

Baharnoori, Moogeh; Bhardwaj, Sanjeev K; Srivastava, Lalit K




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 ...


Assessment of Maternal Toxicity, Embryotoxicity and Teratogenic Potential of Sodium Chlorite in Sprague-Dawley Rats.  

National Technical Information Service (NTIS)

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 inje...

D. Couri C. H. Miller R. J. Bull J. M. Delphia E. M. Ammar




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...


Effect of maternal cholestasis on biliary lipid and bile acid secretion in the infant rat  

Microsoft Academic Search

Partial and reversible impairment of bile formation has been reported to occur in the offspring of rats undergoing common bile duct ligation during the last third of pregnancy. This situation was defined as latent cholestasis of the neonate and was suggested to be related to the multilamellar bodies partially occupying the canalicular lumen. The current study was undertaken to investigate

MY El-Mir; MJ Monte; AI Morales; M Arevalo; MA Serrano; JJ Marin



Prenatal protein restriction leads to a disparity between aortic and peripheral blood pressure in Wistar male offspring.  


A host of animal studies have been used to model the effects of exposure to a low protein diet in utero on adult blood pressure. Collection of systolic blood pressure data by the indirect tail-cuff plethysmography method consistently shows increased pressures in low protein exposed rodent offspring compared to controls, but this technique has been criticised as the associated stress artefacts may confound the observed effects. Conversely, radiotelemetry systems allow unrestrained and continuous monitoring of blood pressure through the awake and sleep phases of the diurnal cycle. In this novel study, we directly compared blood pressure parameters in male offspring from low protein and control-fed dams measured simultaneously using tail-cuff and radiotelemetry systems. Control rats showed a good correlation between tail-cuff and radiotelemetry derived blood pressure data. Conversely, low protein males were relatively hypertensive at 8 weeks of age when measured by tail-cuff, but had significantly lower blood pressure than controls at 12 weeks of age when measured by telemetry. Heart rate and length of systole did not differ between the two groups. Individual stress protocols mimicking those imposed by tail-cuff plethysmography (novel environment, heat, restraint, inflation), caused similar increases in blood pressure and heart rate in control and low protein animals, ruling out an effect of enhanced pressor response to stress following prenatal protein restriction. Instead, an increase in peripheral vascular resistance in these animals is considered possible. Such a disparity between central and peripheral blood pressure measurements could have important clinical implications regarding cardiovascular risk assessment and treatment. PMID:20693295

Swali, Angelina; McMullen, Sarah; Langley-Evans, Simon C



Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat  

PubMed Central

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.

Bagot, Rosemary C.; Zhang, Tie-Yuan; Wen, Xianglan; Nguyen, Thi Thu Thao; Nguyen, Huy-Binh; Diorio, Josie; Wong, Tak Pan; Meaney, Michael J.



Maternal zinc intake of Wistar rats has a protective effect in the alloxan-induced diabetic offspring.  


Zinc has a role in the synthesis, storage, and secretion of insulin, and has been suggested to be beneficial when used in the diabetic state. Effect of zinc intake in pregnant rats has been studied here on diabetized offspring. Pregnant rats were divided in two groups; the control group received normal food and water, and the experimental group received zinc sulfate during pregnancy and 3 weeks after offspring birth. Male offspring from the control (C) and experimental (E) groups were divided each in three groups: C1, fed with normal food and water; C2, diabetized with alloxan; C3, received zinc sulfate; E1, fed with normal food and water; E2, diabetized with alloxan; and E3, receiving zinc sulfate. After 30 days, the histological changes of pancreatic tissues were investigated by light microscopy. Body weight, blood glucose, serum insulin levels, food intake, water intake, and urine quantity were also compared between the groups. Water intake and urine quantity were decreased significantly (p?maternal zinc intake may influence subsequent deleterious effects of diabetes on alloxan-diabetized offspring. PMID:22730079

Yaghmaei, Parichehreh; Esfahani-Nejad, Hamideh; Ahmadi, Ramesh; Hayati-Roodbari, Nasim; Ebrahim-Habibi, Azadeh



Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups  

PubMed Central

There are conflicting data to support the practice of delaying the introduction of allergenic foods into the infant diet to prevent allergy development. This study investigated immune response development after early oral egg antigen (Ovalbumin; OVA) exposure in a rat pup model. Brown Norway (BN) rat pups were randomly allocated into groups: dam reared (DR), DR pups challenged daily (days 4–13) with oral OVA (DR + OVAc), DR pups challenged intermittently (on day 4, 10, 12, and 13) with oral OVA (DR + OVAi), formula-fed pups (FF), and FF pups challenged daily with oral OVA (FF + OVA). Immune parameters assessed included OVA-specific serum IgE, IgG1, and IgA. Ileal and splenic messenger ribonucleic acid (mRNA) expression of transforming growth factor-beta (TGF-?1), mothers against decapentaplegic (Smad) 2/4/7, and forkhead box P3 (Foxp3) were determined. Ileum was stained for TGF-?1 and Smad4. Results. Feeding OVA daily to DR pups maintained systemic and local gut antibody and immunoregulatory marker mRNA responses. Systemic TGF-?1 was lower in DR + OVAi pups compared to DR and DR + OVAc pups. Feeding OVA to FF pups resulted in significantly greater OVA-specific IgE and IgG1, and lower IgA and TGF-?1 and Smad expression compared to DR pups. Conclusions. Early daily OVA exposure in the presence of maternal milk maintains immune markers associated with a regulated immune response, preventing early allergic sensitization.

El-Merhibi, Adaweyah; Lymn, Kerry; Kanter, Irene; Penttila, Irmeli A.



Maternal adaptations to pregnancy in spontaneously hypertensive rats: leptin and ghrelin evaluation  

Microsoft Academic Search

Leptin and\\/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been usedtoevaluate,forthefirsttime,themodificationof leptinand ghrelin both at serum and tissue levels. In SHR, we evaluate plasmaleptinlevelandtissueproteinexpressioninbothplacenta and adipose tissue at the end of gestation (day 20) versus normotensive

Giuseppina Mattace Raso; Giuseppe Bianco; Anna Iacono; Emanuela Esposito; Giuseppina Autore; Maria Carmela Ferrante; Antonio Calignano; Rosaria Meli



Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat  

PubMed Central

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased ?2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to “program” behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

Caldji, Christian; Tannenbaum, Beth; Sharma, Shakti; Francis, Darlene; Plotsky, Paul M.; Meaney, Michael J.



Influences of alkaline ionized water on milk electrolyte concentrations in maternal rats.  


We previously reported that body weight on day 14 after birth in male offspring of rats given alkaline ionized water (AKW) was significantly heavier than that in offspring of rats given tap water (TPW), but no significant difference was noted in milk yield and in suckled milk volume between the two groups. Additionally, the offspring in the AKW group and TPW group were given AKW and TPW, respectively, at weaning, and unexpectedly, the necrotic foci in the cardiac muscle were observed at the 15-week-old age in the AKW group, but not in the TPW group. The present study was designed to clarify the factors which are involved in that unusual increase of body weight and occurrence of cardiac necrosis. Eight dams in each group were given AKW or TPW (control) from day 0 of gestation to day 14 of lactation. The milk samples were collected on day 14 of lactation and analyzed for concentrations of calcium (Ca), sodium (Na), potassium (K), magnesium (Mg) and chloride (Cl). The AKW and TPW were also analyzed. Ca, Na and K levels in milk were significantly higher in the AKW group compared to the TPW group. No significant difference was noted in the Mg and Cl levels between the two groups. These data suggested that the Ca cation of AKW enriched the Ca concentration of the milk and accelerated the postnatal growth of the offspring of rats given AKW. PMID:11201172

Watanabe, T; Kamata, H; Fukuda, Y; Murasugi, E; Sato, T; Uwatoko, K; Pan, I J



Early postnatal maternal separation causes alterations in the expression of ?3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity  

SciTech Connect

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 ?3-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), ?3-adrenergic receptor (?3-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 ?3-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 ?3-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.

Miki, Takanori, E-mail: [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan)] [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan)] [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan)] [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan)] [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan)] [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan)] [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)



Nutrient-Dependent Requirement for SOD1 in Lifespan Extension by Protein Restriction in Drosophila melanogaster  

PubMed Central

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.

Sun, Xiaoping; Komatsu, Toshimitsu; Lim, Jinhwan; Laslo, Mara; Yolitz, Jason; Wang, Cecilia; Poirier, Luc; Alberico, Thomas; Zou, Sige



Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  

PubMed Central

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B12 lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

Kulkarni, Asmita; Dangat, Kamini; Kale, Anvita; Sable, Pratiksha; Chavan-Gautam, Preeti; Joshi, Sadhana



Induction of a rat T cell lymphoma-leukemia by magnesium deficiency--a study of fetal defense against maternal neoplasia.  


If Sprague-Dawley rats, 25-30 days old, are fed a diet containing 4-5 mg% of Mg, about 25% of survivors develop a large tumor of the thymus within 6-12 weeks. The tumor is composed of lymphoblasts, which seem to arise from the thymic reticuloendothelial system and, at times, disseminate as an acute T cell lymphoma-leukemia of unknown etiology. If the tumor cells are transmitted intraperitoneally to rats, 14-16 days pregnant, a local invasive and generalized disease is established in the mother but not in the fetuses or their domain. However, if the neoplastic cells are injected into the fetal domain, they colonize the fetal tissues. The colonization by tumor cells is most impressive in the extravascular structure of the placental labyrinth but not in the placental syncytiotrophoblastic zone at the maternal-placental junction. This raises the question as to whether this zone may functionally mediate not only the well-known absolute intrauterine fetal defense against maternal metastatic neoplasia, but also the defense of the fetus against maternal immunologic rejection. PMID:2739466

Hass, G M; Galt, R M; Laing, G H; Coogan, P S; Maganini, R O; Friese, J A



Maternal fructose and/or salt intake and reproductive outcome in the rat: effects on growth, fertility, sex ratio, and birth order.  


Maternal diet can significantly skew the secondary sex ratio away from the expected value of 0.5 (proportion males), but the details of how diet may do this are unclear. Here, we altered dietary levels of salt (4% salt in the feed) and/or fructose (10% in the drinking water) of pregnant rats to model potential effects that consumption of a "Western diet" might have on maternofetal growth, development, and sex ratio. We demonstrate that excess fructose consumption before and during pregnancy lead to a marked skew in the secondary sex ratio (proportion of males, 0.60; P < 0.006). The effect was not mediated by selective developmental arrest of female embryos or influenced by fetal position in the uterine horn or sex-specific effects on sperm motility, suggesting a direct effect of glycolyzable monosaccharide on the maternal ovary and/or ovulated oocyte. Furthermore, combined excess maternal consumption of salt and fructose-sweetened beverage significantly reduced fertility, reflected as a 50% reduction in preimplantation and term litter size. In addition, we also noted birth order effects in the rat, with sequential implantation sites tending to be occupied by the same sex. PMID:23759309

Gray, Clint; Long, Sophie; Green, Charlotte; Gardiner, Sheila M; Craigon, Jim; Gardner, David S



A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring.  


Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity. PMID:17697422

Bayol, Stéphanie A; Farrington, Samantha J; Stickland, Neil C



Effects of maternal exposure to diethylstilbestrol on epididymal development in rat offspring.  


In our previous study, prenatal diethylstilbestrol (DES) exposure (days 7-21 of gestation) suppressed plasma testosterone levels and histological development in the epididymis of rat offspring. In this study, we measured cell proliferation in epididymal ductules and the expression of steroid hormone receptors and 5alpha-reductase 1 in the epididymis to assess the effect of DES on epididymal development in the offspring. Prenatal DES exposure did not alter the cell division index, but suppressed the expression of androgen receptor mRNA at 15 weeks after birth, and stimulated estrogen receptor alpha mRNA at 6 weeks. These results suggest that prenatal DES exposure results in the retardation of epididymal tissue maturation by disruption of the postnatal expression of steroid hormone receptors. PMID:19346712

Yamamoto, Masako; Kohara, Shinya; Kobayashi, Tetsuo; Shirai, Mitsuyuki; Nisikawa, Osamu; Arishima, Kazuyoshi



Maternal iron deficiency identifies critical windows for growth and cardiovascular development in the rat postimplantation embryo.  


Imbalances in nutrition during pregnancy can lead to long-, as well as short-term consequences, a phenomenon known as fetal programming. However, there is little information about when the fetus is most sensitive to its environment during gestation. We hypothesize that different fetal systems are most vulnerable to nutritional stress during periods of maximal growth and differentiation. We used iron (Fe) deficiency, which causes hypertension in the offspring, to test this hypothesis. We examined development between embryonic day (E) 10.5 and 12.5, when cardiovascular development is maximal, using whole embryo culture. Female rats were fed Fe-deficient or control diet for 4 wk before mating and up to E10.5. The embryos were cultured for 48 h in 95% rat serum collected from males fed either a control or Fe-deficient diet. Growth was impaired and heart size increased in embryos taken from Fe-deficient mothers and cultured in deficient serum compared with control embryos cultured in control serum. To test whether restoring normal Fe levels could reverse these effects, we cultured embryos from control and deficient dams in either control or deficient medium. The yolk sac circulation of embryos from dams fed either diet cultured in deficient medium was less developed, with a thinner and less branched network than that in all embryos cultured in control serum. The heart was enlarged in embryos of deficient dams cultured in deficient serum compared with the heart size of those cultured in control serum. Culturing embryos in control serum reversed these changes. We conclude, therefore, that this period of cardiovascular organogenesis is one of the sensitive windows during which optimal Fe status is critical for normal development. PMID:16614400

Andersen, Henriette S; Gambling, Lorraine; Holtrop, Grietje; McArdle, Harry J



Dynamic changes in lipids and proteins of maternal, fetal, and pup blood and milk during perinatal development in CD and Wistar rats.  


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

McMullin, Tami S; Lowe, Ezra R; Bartels, Michael J; Marty, Mary Sue



Long-Term Effects of Maternal Diabetes on Blood Pressure and Renal Function in Rat Male Offspring  

PubMed Central

Aims/Hypothesis Gestational diabetes mellitus (GDM) is increasing rapidly worldwide. Previous animal models were established to study consequences of offspring after exposure to severe intrauterine hyperglycemia. In this study we are aiming to characterize the blood pressure levels and renal function of male offspring obtained from diabetic mothers with moderate hyperglycemia. Methods We established a rat model with moderate hyperglycemia after pregnancy by a single intraperitoneal injection of streptozotocin (STZ). The male offspring were studied and fed with either normal diet or high salt diet after weaning. Arterial pressure and renal function were measured. Results Arterial pressure of male offspring increased from 12 weeks by exposure to intrauterine moderate hyperglycemia. At 20 weeks, high salt diet accelerated the blood pressure on diabetic offspring compared to diabetic offspring fed with normal diet. We found offspring exposed to intrauterine moderate hyperglycemia had a trend to have a higher creatinine clearance rate and significant increase of urinary N-acetyl-?-D-glucosaminidase (NAG) excretion indicating an early stage of nephropathy progression. Conclusions/Interpretation We observed the high blood pressure level and early renal dysfunction of male offspring obtained from diabetic mothers with moderate hyperglycemia. Furthermore, we investigated high salt diet after weaning on offspring exposed to intrauterine hyperglycemia could exacerbate the blood pressure and renal function. Renin angiotensin system (RAS) plays an important role in hypertension pathogenesis and altered gene expression of RAS components in offspring with in utero hyperglycemia exposure may account for the programmed hypertension. Therefore, our study provides evidence “fetal programming” of maternal diabetes is critical for metabolic disease development.

Yan, Jie; Li, Xin; Su, Rina; Zhang, Kai; Yang, Huixia



Neonatal maternal separation and enhancement of the hypoxic ventilatory response in rat: the role of GABAergic modulation within the paraventricular nucleus of the hypothalamus  

PubMed Central

Neonatal maternal separation (NMS) affects respiratory control development as adult male (but not female) rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. The paraventricular nucleus of the hypothalamus (PVN) is an important modulator of respiratory activity. In the present study, we hypothesized that in awake rats, altered GABAergic inhibition within the PVN contributes to the enhancement of hypoxic ventilatory response observed in rats previously subjected to NMS. During normoxia, the increase in minute ventilation following microinjection of bicuculline (1 mm) within the PVN is greater in NMS versus control rats. These data show that regulation of ventilatory activity related to tonic inhibition of the PVN is more important in NMS than control rats. Microinjection of GABA or muscimol (1 mm) attenuated the ventilatory response to hypoxia (12% O2) in NMS rats only. The higher efficiency of microinjections in NMS rats is supported by results from GABAA receptor autoradiography which revealed a 22% increase in GABAA receptor binding sites within the PVN of NMS rats versus controls. Despite this increase, however, NMS rats still show a larger hypoxic ventilatory response than controls, suggesting that within the PVN the larger number of GABAA receptors either compensate for (1) a deficient GABAergic modulation, (2) an increase in the efficacy of excitatory inputs converging onto this structure, or (3) both. Together, these results show that the life-long consequences of NMS are far reaching as they can compromise the development of vital homeostatic function in a way that may predispose to respiratory disorders.

Genest, Sophie-Emmanuelle; Balon, Norbert; Laforest, Sylvie; Drolet, Guy; Kinkead, Richard



Exposure to AT1 Receptor Autoantibodies during Pregnancy Increases Susceptibility of the Maternal Heart to Postpartum Ischemia-Reperfusion Injury in Rats.  


Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats. PMID:24979132

Wang, Hui-Ping; Zhang, Wen-Hui; Wang, Xiao-Fang; Zhu, Jin; Zheng, Yan-Qian; Xia, Qin; Zhi, Jian-Ming



Differential effects of osmotic and SSR149415 challenges in maternally separated and control rats: the role of vasopressin on spatial learning.  


Maternal separation (MS) has been demonstrated to up-regulate the hypothalamic vasopressin (VP) system. Intracerebrally released VP has been demonstrated to affect several types of animal behaviour, such as active/passive avoidance, social recognition, and learning and memory. However, the role of VP in spatial learning remains unclear. In the present study, we investigated the effects of an osmotic challenge and a V1b receptor-specific (V1bR) antagonist, SSR149415, on spatial learning of maternally separated and animal facility reared (AFR) adult male Wistar rats. The osmotic challenge was applied by injecting a hypertonic saline solution, 1h before the Morris water maze test (MWM). V1bR antagonist SSR149415 (5mg/kg) was injected i.p. twice (1h and 30 min) previous to the MWM. A combined treatment with both osmotic challenge and the SSR149415 was applied to the third group whereas rats for basal condition were injected with isotonic saline. Under basal condition no differences between AFR and MS groups were observed. MS rats showed severe impairment during the MWM after the osmotic challenge, but not after the administration of SSR149415. For AFR rats, the opposite phenomenon was observed. The joint application of SSR149415 and osmotic challenge restored the spatial learning ability for both groups. The differential impairment produced by osmotic stress-induced up-regulation and SSR149415 induced V1bR blockage in MS and control rats suggested that VP involvement in spatial learning depends on the individual intrinsic ligand-receptor functional state. PMID:22982556

Hernandez, Vito S; Ruíz-Velazco, Silvia; Zhang, Limei



Effects of maternal lead exposure on central nervous system maturation in postnatal rats  

SciTech Connect

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.

Coleman, J.C.



Maternal deprivation and handling modify the effect of the dopamine D3 receptor agonist, BP 897 on morphine-conditioned place preference in rats  

Microsoft Academic Search

Rationale  Maternal deprivation and handling can lead to a vulnerability to opiate dependence. However, the involvement of the dopamine\\u000a D3 receptors has not been investigated.\\u000a \\u000a \\u000a \\u000a Objectives  This study analysed the effects of a selective partial D3 receptor agonist, BP 897, on morphine-conditioned place preference\\u000a (CPP) in deprived and handled rats.\\u000a \\u000a \\u000a \\u000a Materials and methods  The effects of BP 897 were studied on the expression

Vincent Vazquez; Stéphanie Weiss; Bruno Giros; Marie-Pascale Martres; Valérie Daugé



Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring  

PubMed Central

Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague–Dawley rats were exposed to dibutyl phthalate (DBP; from gestational day (GD) 14.5 to postnatal day (PND) 6) or diethylstilbestrol (DES; from GD14.5 to GD16.5) during a short gestational/lactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.

Ivell, Richard; Heng, Kee; Nicholson, Helen; Anand-Ivell, Ravinder



Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring  

PubMed Central

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.

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.



Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats.  


The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on fetal brain growth and neurobehavioral development in early developmental stages were investigated using rat offspring. TCDD in corn-oil (0.1microg/kg) was orally administrated to the dams from the 9th to 19th gestational day. When TCDD effects on the fetal brain weight were analyzed on the 19th gestational day, weight ratio of the brain to the whole body, and that of the forebrain without the cerebral cortex to the whole brain were larger in the exposed group than those of the control group, suggesting premature fetal brain development. TCDD effects on motor functions were investigated using newborns in an inclined plane task. Motor development assessed by righting response on an inclination was delayed in the exposed offspring in the 8th-12th postnatal day, especially in male. Also, TCDD effects on active avoidance behavior in a shuttle box were investigated using the offspring after weaning. Latency in the active avoidance learning was longer, and locomotor activity was reduced in the exposed male offspring in the 41st-44th postnatal day. The results demonstrated that maternal TCDD exposure delayed fetal brain growth and neurodevelopment of the offspring in early stage, especially in male rats. PMID:17669605

Nishijo, Muneko; Kuriwaki, Jun-Ichi; Hori, Etsuro; Tawara, Kenji; Nakagawa, Hideaki; Nishijo, Hisao



Experimental evaluation of the impact of maternal consumption of aqueous leaf extract of Hybanthus enneaspermus on pregnancy in Sprague Dawley rats.  


The impact of aqueous leaf extract of Hybanthus enneaspermus (HEaq) on pregnancy factors and litter survival was investigated in Sprague Dawley (SD) rat. Control group received distilled water while the test group received 2g/kg body weight of HEaq orally. Blood samples were collected on days one and twenty of pregnancy for total blood count, serum thyroid hormone, thyroid stimulating hormone (TSH) and thyrotropin releasing hormone (TRH) assay. Half the number of rats in each group was sacrificed on day nineteen of pregnancy and the placenta and foetus were removed and weighed. The second half carried their pregnancy to term. Number and weights of litter were recorded at birth and the litter were also subjected to righting reflex test. Post-natal survival rate was determined for each group while effect of HEaq was also examined in-vivo on the activities of pregnant myometrial muscle. HEaq significantly decreased (p<0.05) foetal weight, placenta weight, foetal growth and survival, number and weights of litter at birth, maternal serum triiodotyroxine T3 and TSH level. Mean corpuscular haemoglobin, white blood cell count, platelet count and lipid profile were significantly increased (P<0.05). HEaq increased the frequency and percentage contraction of gravid myometrial muscle in a dose dependent manner. Maternal consumption of aqueous leaf extract of Hybanthus enneaspermus adversely affected pregnancy and development of the foetus, as it precipitated resorption of developing foetus and reduced size and weight of litter at term. PMID:24146452

Olubajo, Awobajo Funmileyi; Adefunke, Adegoke Olufeyisipe; Olubusola, Iranloye Bolanle; Ibilola, Olatunji-Bello Ibiyemi



Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1.  


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

Sun, Xiu-Min; Tu, Wen-Qiang; Shi, Yan-Wei; Xue, Li; Zhao, Hu



Oral Leptin Treatment in Suckling Rats Ameliorates Detrimental Effects in Hypothalamic Structure and Function Caused by Maternal Caloric Restriction during Gestation  

PubMed Central

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.

Konieczna, Jadwiga; Garcia, Ana Paula; Sanchez, Juana; Palou, Mariona; Palou, Andreu; Pico, Catalina



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

Microsoft Academic Search

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%

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




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...


Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat.  


Nutrient restriction in pregnancy has been shown to programme adult obesity. Modulation of feeding behaviour may provide a mechanism through which obesity may be programmed. Pregnant Wistar rats were fed either a control diet or a low-protein (LP) diet throughout gestation. Their offspring were allocated to a self-selected-diet protocol to assess appetite and food preferences at 12 and at 30 weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods by 12-week-old rats indicated that the prenatal environment influenced feeding behaviour. Both male and female offspring of LP-fed mothers consumed significantly more of the high-fat (P<0.001) and significantly less (P<0.02) of the high-carbohydrate food than the control animals. Female, but not male, offspring of LP-fed rats failed to adjust food intake to maintain a constant energy intake and had higher fat (P<0.005) and energy intakes (P<0.05) than control female rats. At 30 weeks of age there were no differences in the pattern of food selection between the two groups of animals. Male offspring of LP-fed rats had significantly more gonadal fat than control animals (P<0.05), but analysis of total body fat content indicated that there was no significant difference in overall adiposity. The present study suggests that in young adults at least, early life exposure to undernutrition determines a preference for fatty foods. Maternal nutrition may thus promote changes in systems that are involved in control of appetite or the perception of palatability. PMID:15469656

Bellinger, Leanne; Lilley, Christina; Langley-Evans, Simon C



Maternal Voluntary Exercise during Pregnancy Enhances the Spatial Learning Acquisition but not the Retention of Memory in Rat Pups via a TrkB-mediated Mechanism: The Role of Hippocampal BDNF Expression  

PubMed Central

Objective(s): The effect of maternal voluntary exercise on hippocampal BDNF level in rat offspring was studied. In addition, the possible role of hippocampal BDNF receptors in maternal exercise induced enhancement of learning in the rat pups was investigated. Materials and Methods: Pregnant rats have been randomly assigned to sedentary control or voluntary exercise groups. Each of the exercising pregnant rats was given access to a cage that was equipped with a running wheel until the end of their pregnancy. On post natal day (PND) 36, two groups consisted of 7 male rat pups in each group from sedentary or exercised mothers were sacrificed and the hippocampus was dissected for BDNF proteins level determination. Also, bilateral injection of K252a to the hippocampus was used to block the hippocampal BDNF action on PND59 in the rat pups. Results: Voluntary exercise during pregnancy significantly increased the level of BDNF protein in the hippocampus of the rat pups on PND36 compared to the control group (P=0.048). Inhibiting BDNF action abolished the exercise-induced improvement of learning acquisition in offspring in training trials (P=0.0001). No difference was observed in the platform location latency and the time spent in the target in the probe test between two groups. Conclusion: This study demonstrates that voluntary exercise during pregnancy via a TrkB-mediated mechanism enhances the spatial learning acquisition, however, not the retention of memory in the rat pups.

M. Akhavan, Maziar; Miladi-Gorji, Hossein; Emami-Abarghoie, Mitra; Safari, Manouchehr; Sadighi-Moghaddam, Bizhan; A. Vafaei, Abbas; Rashidy-Pour, Ali



Maternal nutrition and development of intestinal functions: II--Effect of feeding high protein and high fat diets to lactating rats.  


Effects of feeding high-protein (HP) and high-fat (HF) diets to lactating rats have been studied on the development of microvillus membrane enzymes and glycosylation in suckling rats. The activities of sucrase and lactase were significantly (P less than 0.01) decreased in the pups reared on HP fed dams. Alkaline phosphatase (AP), leucine aminopeptidase (LAP) and gamma-glutamyl-transpeptidase (gamma-GTP) activities were essentially similar in HP and pair-fed groups. Pups reared on dams fed HF-diet, revealed nearly a 20% increase in disaccharidase levels and a significant (P less than 0.05) decrease in AP activity compared to the pair-fed controls. The activities of LAP and GTP were unaffected under these conditions. Sialic acid content was unaltered, however, fucose level of the membranes was significantly reduced in pups nursed by mothers fed HP-(P less than 0.05) or HF-(P less than 0.01) diet. The binding of 125I-labelled wheat germ agglutinin and Ulex europeus agglutinin was in agreement to the data on sialic acid and fucose contents of the membranes. The binding of peanut agglutinin to microvillus membranes was enhanced by 31% and 21% in HP and HF groups, respectively. These findings suggest that the quality of maternal nutrition affects the enzymes and glycosylation of brush-borders in developing rat intestine. PMID:2253972

Jaswal, V M; Babbar, H S; Mann, D S; Mahmood, A



Metabolic conversion of intra-amniotically-injected deuterium-labeled essential fatty acids by fetal rats following maternal n-3 fatty acid deficiency.  


Accumulation of polyunsaturated fatty acids (PUFA) in the fetal brain is accomplished predominantly via a highly selective flow of docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid (20:4n-6, AA) through the placenta. Little is known regarding the endogenous capability of the fetus to generate its own DHA and AA from lower homologues such as linolenic (18:3n-3, ALA) and linoleic (18:2n-6, LA) acids, respectively. Deuterium-labeled d5-ALA and d5-LA at millimolar concentrations were injected directly into the amniotic fluid in order to investigate maternal-independent metabolic conversion of the stable isotopes in brain and liver of the fetus near delivery. After 48h under adequate maternal diet, the levels of d5-ALA metabolites in the fetal brain and fetal liver were 45±2.2 pmol/mg and 86±4 pmol/mg of which 79% and 63.6% were comprised of d5-DHA. At this time point, incorporation of d5-LA metabolites was 103±5 pmol/mg and 772±46 pmol/mg for brain and liver, of which 50% and 30% were comprised of d5-AA. Following sustained maternal dietary ALA deficiency, the levels of total d5-ALA derived metabolites in the fetal brain and fetal liver were increased to 231 pmol/mg and 696 pmol/mg of which 71% and 26% were comprised of d5-DHA. From the time course and relative rates of d5-ALA precursor displacement by d5-DHA in cellular phosphoglycerides, it is concluded that the fetal rat brain can generate its own DHA from its d5-ALA precursors particularly under dietary stress. PMID:24960100

Yavin, Ephraim; Lin, Yu Hong; Brand, Annette; Salem, Norman



Inflammatory response and oxidative stress in developing rat brain and its consequences on motor behavior following maternal administration of LPS and perinatal anoxia.  


Cerebral palsy (CP) is a disorder of locomotion, posture and movement that can be caused by prenatal, perinatal or postnatal insults during brain development. An increased incidence of CP has been correlated to perinatal asphyxia and maternal infections during gestation. The effects of maternal exposure to low doses of bacterial endotoxin (lipopolysaccharide, LPS) associated or not with perinatal anoxia (PA) in oxidative and inflammatory parameters were examined in cerebral cortices of newborns pups. Concentrations of TNF-?, IL-1, IL-4, SOD, CAT and DCF were measured by the ELISA method. Other newborn rats were assessed for neonatal developmental milestones from day 1 to 21. Motor behavior was also tested at P29 using open-field and Rotarod. PA alone only increased IL-1 expression in cerebral cortex with no changes in oxidative measures. PA also induced a slight impact on development and motor performance. LPS alone was not able to delay motor development but resulted in changes in motor activity and coordination with increased levels of IL-1 and TNF-? expression associated with a high production of free radicals and elevated SOD activity. When LPS and PA were combined, changes on inflammatory and oxidative stress parameters were greater. In addition, greater motor development and coordination impairments were observed. Prenatal exposure of pups to LPS appeared to sensitize the developing brain to effects of a subsequent anoxia insult resulting in an increased expression of pro-inflammatory cytokines and increased free radical levels in the cerebral cortex. These outcomes suggest that oxidative and inflammatory parameters in the cerebral cortex are implicated in motor deficits following maternal infection and perinatal anoxia by acting in a synergistic manner during a critical period of development of the nervous system. PMID:24140242

Stigger, Felipe; Lovatel, Gisele; Marques, Marília; Bertoldi, Karine; Moysés, Felipe; Elsner, Viviane; Siqueira, Ionara Rodrigues; Achaval, Matilde; Marcuzzo, Simone



Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver????  

PubMed Central

Poor prenatal nutrition, acting through epigenetic processes, induces persistent changes in offspring phenotype. We investigated the effect of maternal fat intake on polyunsaturated fatty acid (PUFA) status and on the epigenetic regulation of Fads2, encoding ?6 desaturase (rate limiting in PUFA synthesis), in the adult offspring. Rats (n=6 per dietary group) were fed either 3.5% (w/w), 7% (w/w) or 21% (w/w) butter or fish oil (FO) from 14 days preconception until weaning. Offspring (n=6 males and females per dietary group) were fed 4% (w/w) soybean oil until postnatal day 77. 20:4n-6 and 22:6n-3 levels were lower in liver phosphatidylcholine (PC) and phosphatidylethanolamine and plasma PC (all P<.0001) in offspring of dams fed 21% than 3.5% or 7% fat regardless of type. Hepatic Fads2 expression related inversely to maternal dietary fat. Fads2 messenger RNA expression correlated negatively with methylation of CpGs at ?623, ?394, ?84 and ?76 bases relative to the transcription start site (all P<.005). Methylation of these CpGs was higher in offspring of dams fed 21% than 3.5% or 7% fat; FO higher than butter. Feeding adult female rats 7% fat reduced 20:4n-6 status in liver PC and Fads2 expression and increased methylation of CpGs ?623, ?394, ?84 and ?76 that reversed in animals switched from 7% to 4% fat diets. These findings suggest that fat exposure during development induces persistent changes, while adults exhibit a transient response, in hepatic PUFA status in offspring through epigenetic regulation of Fads2. Thus, epigenetic regulation of Fads2 may contribute to short- and long-term regulation of PUFA synthesis.

Hoile, Samuel P.; Irvine, Nicola A.; Kelsall, Christopher J.; Sibbons, Charlene; Feunteun, Aurelie; Collister, Alex; Torrens, Christopher; Calder, Philip C.; Hanson, Mark A.; Lillycrop, Karen A.; Burdge, Graham C.



Maternal "junk-food" feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring  

PubMed Central

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: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 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.

Ong, Z. Y.; Muhlhausler, B. S.



Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure  

PubMed Central

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.

Bossi, Rossana; Vinggaard, Anne Marie; Taxvig, Camilla; Boberg, Julie; Bonefeld-J?rgensen, Eva Cecilie



Levels of pesticides and their metabolites in Wistar rat amniotic fluids and maternal urine upon gestational exposure.  


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

Bossi, Rossana; Vinggaard, Anne Marie; Taxvig, Camilla; Boberg, Julie; Bonefeld-Jørgensen, Eva Cecilie



Frequency of maternal licking and grooming correlates negatively with vulnerability to cocaine and alcohol use in rats  

PubMed Central

Because licking and grooming behavior of dams with pups can influence some behaviors of pups when they are adults, we tested if licking and grooming scores in a maternal separation protocol correlated with cocaine or ethanol self-administration in the pups as adults. The protocol produced litters that were separated from dams for 0 (MS0), 15 (MS15) or 180 (MS180) min, and a nonhandled (NH) group as well. Self-administration of both drugs as shown in earlier studies was lowest in the MS15 group, highest in the NH group and intermediate in the other groups. Licking and grooming scores correlated negatively with drug intake and suggests that maternal care of pups can influence drug use in pups when they are adults.

Francis, D.D.; Kuhar, M.J.



Maternal deprivation in rats is associated with corticotropin releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood  

PubMed Central

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.

Chen, Jun; Evans, Andrew N.; Liu, Ying; Honda, Masaru; Saavedra, Juan M.; Aguilera, Greti



Variable maternal stress in rats alters locomotor activity, social behavior, and recognition memory in the adult offspring.  


Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral signs that are similar to those manifested in several neuropsychiatric disorders such as deficits in attention and inhibitory control, and impairments in memory-related task performance. The purpose of the study described here was to conduct a comprehensive battery of tests to further characterize the behavioral phenotype of PNS rats as well as to evaluate the sensitivity of the model to therapeutic interventions (i.e., to compounds previously shown to have therapeutic potential in neuropsychiatric disorders). The results of this study indicated that PNS in rats is associated with: 1) increased locomotor activity and stereotypic behaviors, 2) elevated sensitivity to the psychostimulant amphetamine, 3) increased aggressive behaviors toward both adult and juvenile rats and 4) delay-dependent deficits in recognition memory. There was no evidence that PNS rats exhibited deficits in other areas of motor function/learning, sensorimotor gating, spatial learning and memory, social withdrawal, or anhedonia. In addition, the results revealed that the second generation antipsychotic risperidone attenuated amphetamine-related increases in locomotor activity in PNS rats; however, the effect was not sustained over time. Furthermore, deficits in recognition memory in PNS rats were attenuated by the norepinephrine reuptake inhibitor, atomoxetine, but not by the ?7 nicotinic acetylcholine receptor partial agonist, GTS-21. This study supports the supposition that important phenomenological similarities exist between rats exposed to PNS and patients afflicted with neuropsychiatric disorders thus further establishing the face validity of the model for evaluating potential therapeutic interventions. PMID:23287801

Wilson, Christina A; Terry, Alvin V



Cellular immune responses of nutritionally stressed juvenile cotton rats (Sigmodon hispidus) during acute benzene exposure  

Microsoft Academic Search

Wild juvenile cotton rats (Sigmodon hispidus) were used in this study to examine the effects of exposure to cyclophosphamide (CY) or differing levels of benzene on selected measures of cellular immunity following dietary protein restriction. Benzene caused marginal immunotoxicity as indicated by suppressed splenocyte proliferation and total circulating neutrophils. Cyclophosphamide and also crude protein restriction induced severe immune lesions manifested

S. T. McMurry; R. L. Lochmiller; M. R. Vestey; C. W. Qualls



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

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.

Beltrand, J.; Sloboda, D. M.; Connor, K. L.; Truong, M.; Vickers, M. H.



Maternal immunization.  


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

Chu, Helen Y; Englund, Janet A



Maternal and Fetal Insulin-Like Growth Factor System and Embryonic Survival During Pregnancy in Rats: Interaction between Dietary Chromium  

Microsoft Academic Search

Chromium (Cr) depletion may exacerbate hyperglycemia and negative outcomes of pregnancy in the streptozotocin (STZ) diabetic pregnant rat model through the regulation of the insulin-like growth factor (IGF) system. To test this hypothesis, 40 female rats, all fed a low Cr diet (i.e., 70 mg Cr\\/kg diet ) from 21 d of age, were randomly assigned one of four treatments,

M. T. Spicer; B. J. Stoecker; T. Chen; L. J. Spicer


Maternal oral consumption of morphine increases Bax/Bcl-2 ratio and caspase 3 activity during early neural system development in rat embryos.  


Maternal morphine consumption has been shown to result in physical and neurobehavioral defects in fetus and offspring, but the underlying molecular mechanisms of these defects remain unclear. Regarding the critical role of apoptosis in normal development of central nervous system, the present study was designed to investigate the effect of intrauterine morphine exposure on programmed cell death of neuroblasts during the early development of neural system. Pregnant Wistar rats received morphine sulfate through drinking water at the concentration of 0.01 mg/ml (20 ml water per day for each rat) from the first day of gestation to the time of sampling. Control groups received tap water. Control and morphine-treated pregnant rats, each in five separated groups, were killed on gestational days 9.5 to 13.5, and the embryos were taken out, fixed, and embedded in paraffin. Immunohistochemical assay was used to reveal the protein expression of Bax, Bcl2, and the activation of caspase 3. The results showed a significant increase in Bax immunoreactivity in all of the mentioned embryonic days (E9.5 to E13.5) and a significant decrease in Bcl-2 immunoreactivity at days E10.5 and E12.5 in morphine-treated groups compared with control. Data analysis revealed that Bax/Bcl2 ratio was increased in all of the morphine-exposed groups. Consistent with these results, immunostaining of cleaved caspase 3 showed a significant increase at days E11.5 to E13.5. These findings suggest that morphine exposure during the first embryonic days may enhance the susceptibility of neuroblasts to apoptosis by upregulating the ratio of Bax to Bcl-2 protein expression and increasing downstream caspase-3 activity. The increased probability of neuroblast apoptosis may be the cause of morphine-induced defects in the central nervous system development and its structural and neurobehavioral consequences. PMID:19936637

Nasiraei-Moghadam, Shiva; Kazeminezhad, Behrang; Dargahi, Leila; Ahmadiani, Abolhassan



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

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.

Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro



Maternal Neurofascin-Specific Autoantibodies Bind to Structures of the Fetal Nervous System during Pregnancy, but Have No Long Term Effect on Development in the Rat  

PubMed Central

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children.

Hochmeister, Sonja; Pekar, Thomas; Lindner, Maren; Kitic, Maja; Haindl, Michaela; Storch, Maria; Fazekas, Franz; Linington, Christopher



Maternal omega 3 fatty acid supplementation during pregnancy to a micronutrient-imbalanced diet protects postnatal reduction of brain neurotrophins in the rat offspring.  


An altered one carbon cycle (folic acid, vitamin B(12)) and omega 3 fatty acid metabolism during pregnancy can increase the risk for neurodevelopmental disorders in the offspring. Our earlier studies have shown that a maternal diet imbalanced with micronutrients like folic acid, vitamin B(12) reduces levels of brain docosahexaenoic acid (DHA) and neurotrophins in the offspring at birth. The present study examines whether these effects can be reversed by a postnatal diet. Pregnant female rats were divided into six treatment groups at two levels of folic acid both in the presence and absence of vitamin B(12). Omega 3 fatty acid supplementation was given to the vitamin B(12)-deficient groups. Following delivery, eight dams from each group were randomly shifted back to control and remaining eight continued on the same treatment diet. Plasma homocysteine levels could be normalized by a postnatal control diet. Brain DHA levels were similar in all the groups irrespective of the diet consumed during lactation. Brain-derived nerve growth factor (BDNF) and nerve growth factor (NGF) levels were lower in both the vitamin B(12)-deficient groups even after consuming a diet with normal levels of vitamin B(12) during lactation (p<0.05 for all) indicating that the effects of maternal programing with respect to neurotrophins cannot be reversed by a postnatal diet. Our findings for the first time suggest that omega 3 fatty acid supplementation to a micronutrient-imbalanced diet, during pregnancy and lactation protects the levels of BDNF and NGF. This may have significant implications in the development of psychiatric disorders/cognitive deficits in later life. PMID:22579981

Sable, P S; Dangat, K D; Joshi, A A; Joshi, S R



Effects of Post-coital Administration of Alkaloids from Senna alata (Linn. Roxb) Leaves on some Fetal and Maternal Outcomes of Pregnant Rats  

PubMed Central

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 (143.99±1.21 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.

Yakubu, Musa Toyin; Musa, Isa Fakai



Prenatal Nicotine and Maternal Deprivation Stress De-Regulate the Development of CA1, CA3, and Dentate Gyrus Neurons in Hippocampus of Infant Rats  

PubMed Central

Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC), postnatal maternal deprivation (MD) or the combination of the two (NIC+MD) to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14) pups, MD increased pyramidal neurons, however, in dentate gyrus (DG), decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

Wang, Hong; Gondre-Lewis, Marjorie C.



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.  


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

Latouche, Celine; Heywood, Sarah E; Henry, Sarah L; Ziemann, Mark; Lazarus, Ross; El-Osta, Assam; Armitage, James A; Kingwell, Bronwyn A



Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.  


Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage. PMID:10080402

Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P



Depression-like state in maternal rats induced by repeated separation of pups is accompanied by a decrease of cell proliferation and an increase of apoptosis in the hippocampus  

Microsoft Academic Search

Stressful experiences, such as an unsatisfactory mother–infant relationship after delivery, can induce depressive disorders, and it is well-known that stressors impair memory function. The hippocampus plays a crucial role in memory processes. In the present study, we determined whether a depressed-like state induced by repeated separation of pups affects the memory capability of the maternal rats. We also determined the

Yun-Hee Sung; Mal-Soon Shin; Sehyung Cho; Hyung-Hwan Baik; Byung-Kwan Jin; Hyun-Kyung Chang; Eun-Kyu Lee; Chang-Ju Kim



Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation.  


Maternal overnutrition during suckling period is associated with increased risk of metabolic disorders in the offspring. We aimed to assess the effect of Vitis vinifera L. grape skin extract (ACH09) on cardiovascular and metabolic disorders in adult male offspring of rats fed a high-fat (HF) diet during lactation. Four groups of female rats were fed: control diet (7% fat), ACH09 (7% fat plus 200 mg kg(-1) d(-1) ACH09 orally), HF (24% fat), and HF+ACH09 (24% fat plus 200 mg kg(-1) d(-1) ACH09 orally) during lactation. After weaning, all male offspring were fed a control diet and sacrificed at 90 or 180 days old. Systolic blood pressure was increased in adult offspring of HF-fed dams and ACH09 prevented the hypertension. Increased adiposity, plasma triglyceride, glucose levels and insulin resistance were observed in offspring from both ages, and those changes were reversed by ACH09. Expression of insulin cascade proteins IRS-1, AKT and GLUT4 in the soleus muscle was reduced in the HF group of both ages and increased by ACH09. The plasma oxidative damage assessed by malondialdehyde levels was increased, and nitrite levels decreased in the HF group of both ages, which were reversed by ACH09. In addition, ACH09 restored the decreased plasma and mesenteric arteries antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase in the HF group. In conclusion, the treatment of HF-fed dams during lactation with ACH09 provides protection from later-life hypertension, body weight gain, insulin resistance and oxidative stress. The protective effect ACH09 may involve NO synthesis, antioxidant action and activation of insulin-signaling pathways. PMID:24183306

Resende, Angela C; Emiliano, Andréa F; Cordeiro, Viviane S C; de Bem, Graziele F; de Cavalho, Lenize C R M; de Oliveira, Paola Raquel B; Neto, Miguel L; Costa, Cristiane A; Boaventura, Gilson T; de Moura, Roberto S



Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hippocampal-dependent memory in old rats.  


Exposure to chronic stress during the neonatal period is known to induce permanent long-term changes in the central nervous system and hipothalamic-pituitary-adrenal axis reactivity that are associated with increased levels of depression, anxiety, and cognitive impairments. In rodents, a validated model of early life stress is the maternal separation (MS) paradigm, which has been shown to have long-term consequences for the pups that span to adulthood. We hypothesized that the early life stress-associated effects could be exacerbated with aging, because it is often accompanied by cognitive decline. Using a MS model in which rat pups were separated from their mothers for 3 hours daily, during postnatal days 2-14, we evaluated the long-term functional consequences to aged animals (70-week-old), by measuring synaptic plasticity and cognitive performance. The baseline behavioral deficits of aged control rats were further exacerbated in MS animals, indicating that early-life stress induces sustained changes in anxiety-like behavior and hippocampal-dependent memory that are maintained much later in life. We then investigated whether these differences are linked to impaired function of hippocampal neurons by recording hippocampal long-term potentiation from Schaffer collaterals/CA1 synapses. The magnitude of the hippocampal long-term potentiation induced by high-frequency stimulation was significantly lower in aged MS animals than in age-matched controls. These results substantiate the hypothesis that the neuronal and endocrine alterations induced by early-life stress are long lasting, and are able to exacerbate the mild age-associated deficits. PMID:24559649

Sousa, Vasco C; Vital, Joana; Costenla, Ana Rita; Batalha, Vânia L; Sebastião, Ana M; Ribeiro, Joaquim A; Lopes, Luísa V



Transient suppression of late-stage neuronal progenitor cell differentiation in the hippocampal dentate gyrus of rat offspring after maternal exposure to nicotine.  


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 ?7 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

Ohishi, Takumi; Wang, Liyun; Akane, Hirotoshi; Shiraki, Ayako; Itahashi, Megu; Mitsumori, Kunitoshi; Shibutani, Makoto



Labeling of amoeboid microglial cells and intraventricular macrophages in fetal rats following a maternal injection of a fluorescent dye  

Microsoft Academic Search

Amoeboid microglial cells (AMC) in fetal brains were labeled by rhodamine B isothiocyanate (RhIc) when injected intravenously or intraperitoneally into mother rats at late stage of pregnancy. The fluorescent cells were immunostained with antibodies OX-42 and OX-18 that recognize complement type 3 (CR3) receptors and major histocompatibility complex class I (MHC-I) surface antigen, respectively. RhIc-labeled AMC were first observed in

Yong-Biao Li; Charanjit Kaur; Eng-Ang Ling



The Effects of Maternal Phlebotomy and Orally-Administered Erythropoietin (Ep) on Erythropoiesis in the Suckling Rat  

Microsoft Academic Search

Erythropoiesis was stimulated in 2- to 5-day-old neonatal rats suckled by phlebotomized mothers. This was established by increases in: hemoglobin levels, mean corpuscular hemoglobin concentration and percentages of peripheral reticulocytes. The oral administration of cow milk containing 4 IU human erythropoietin (Ep) to 10-day-old normal neonates for 4 days induced a reticulocytosis. Significant amounts of Ep appeared in the plasma

Robert D. Carmichael; Albert S. Gordon; Joseph LoBue



Maternal Care during Infancy Regulates the Development of Neural Systems Mediating the Expression of Fearfulness in the Rat  

Microsoft Academic Search

The mothers of infant rats show individual differences in the frequency of licking\\/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN

Christian Caldji; Beth Tannenbaum; Shakti Sharma; Darlene Francis; Paul M. Plotsky; Michael J. Meaney



Neurobehavioral and metabolic long-term consequences of neonatal maternal deprivation stress and adolescent olanzapine treatment in male and female rats.  


Early maternal deprivation (MD), 24h of dam-litter separation on postnatal day (PND) 9, has been proposed as a suitable animal model to investigate some neuropsychiatric disorders with a base in neurodevelopment that also compromises metabolic and endocrine homeostasis. Atypical antipsychotics are frequently prescribed to children and adolescents as first-line treatment for several mental disorders despite the adverse metabolic effects frequently reported. However, persistent long-term effects after adolescent drug therapy have been scarcely investigated. In the present study we aimed to investigate the long-lasting metabolic and behavioral effects of MD in combination with the administration of an atypical antipsychotic, i.e. olanzapine, during adolescence. For that purpose, male and female Wistar rats not exposed (control group, Co) and exposed to the MD protocol were administered with oral olanzapine (Olan, 7.5mg/kg/day) or vehicle (Vh, 1mM acetic acid) in drinking water from PND 28 to PND 49. Body weight gain, glycaemia and plasma triglyceride (TG) levels were evaluated as relevant metabolic parameters. MD significantly diminished body weight gain, while Olan administration only induced a subtle decrease in body weight gain among female animals in the long-term. Olan discontinuation decreased plasma TG levels in adult rats, an effect that was counteracted by neonatal exposure to the MD protocol. Both MD and Olan treatment impaired cognitive function in the novel object recognition test, although no interaction between treatments was observed. Neither MD nor Olan administration affected psychotic-related symptoms evaluated in the prepulse inhibition task, although animals treated with Olan showed an increased reactivity to the first acoustic stimulus. MD diminished the corticosterone stress-induced response among females, and reduced the expression of CB1 receptors in the hippocampus of both male and female rats. Notably, Olan administration tended to counterbalance these two MD-induced effects (i.e. corticosterone response and CB1 receptor expression). Present findings provide evidence for the long-lasting effects of neonatal MD and Olan administration during adolescence, and suggest some sex-dependent interactions between these two protocols. Further research on the interactions between early life stress and antipsychotic drugs is urgently needed, and sex differences should be consistently considered both in animal models and in translation to human studies. PMID:21819999

Llorente-Berzal, Alvaro; Mela, Virginia; Borcel, Erika; Valero, Manuel; López-Gallardo, Meritxell; Viveros, Maria-Paz; Marco, Eva M



[Maternal mortality].  


Every year, more than 585,000 women die throughout the world from pregnancy-related causes. Pregnancy complications occur in all countries, but nearly all the resulting deaths occur in developing countries. The maternal mortality rate in Ecuador, estimated by applying the sister survival method to survey data for 1988-94, was 160/100,000 live births. Approximately 460 women thus die each year from maternal causes. The Program of Action of the 1994 International Conference on Population and Development established that countries with intermediate levels of maternal mortality should strive to reduce rates to below 100/100,000 by the year 2005 and to below 60/100,000 by the year 2015. Ecuador's Plan for Reduction of Maternal Mortality will involve the cooperation of national and international organizations, aided by the president of Ecuador and under the leadership of the first lady. The initiative will require commitment from all sectors and individuals directly or indirectly influencing women's health. PMID:12178219



Maternal Employment  

ERIC Educational Resources Information Center

The overwhelming evidence from years of research is that maternal employment, by itself, has little influence on the behaviors of children. More relevant issues are: mother's reasons for working, family's acceptance of mother's employment, quality of substitute child care, family's social and emotional health, and economic conditions. (Author/AJ)

Clark, Sam



Effect of single and repeated injections of selective D2-antagonist clebopride on maternal behavior of albino rats.  


This study examined the effect of clebopride at low concentration that did not modify the motor activity on the parental care in female albino rats. Single injection of the drug attenuated the parental care reactions on postinjection minute 20, but not one day thereafter. The daily injection of the drug during the post partum period (1-6 days) resulted in significantly more pronounced and stable effects. The data obtained substantiated the views on the major contribution of D(2)-receptors in the development of behavioral manifestations of puerperal depression. PMID:22816078

Tanaeva, K K; Dobryakova, Yu V; Dubynin, V A; Kamensky, A A



Persistence of methylated purines in the DNA of various rat fetal and maternal tissues and carcinogenesis in the offspring following a single transplacental dose of N-methyl-N-nitrosourea.  


Formation and loss of methylated purines in DNA of various fetal and maternal tissues were measured up to 7 days following intravenous administration of N-[14C]methyl-N-nitrosourea to rats on the 21st day of gestation. Methylation products were detected in all tissues examined, the level in maternal liver being higher than in other tissues. The concentrations of 7-methylguanine and 3-methyladenine decreased faster in fetal than in corresponding maternal tissues, due to a higher rate of DNA synthesis in fetal tissues, as determined by incorporation of labelled thymidine. Removal of the promutagenic DNA lesion O6-methylguanine was most efficient in maternal and fetal liver; but it was very poorly repaired in kidney and brain. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of fetal brain. The principal targets for the transplacental carcinogenic effect of N-methyl-N-nitrosourea under these experimental conditions were fetal neurogenic tissue and kidney; and malignant tumors developed at these sites in 31-34% and 15-16% of male and female descendants, respectively. These results support the concept that a complex interaction between DNA alkylation, repair and replication is the molecular basis of initiation of carcinogenesis by alkylating agents. PMID:6862687

Likhachev, A J; Alekandrov, V A; Anisimov, V N; Bespalov, V G; Korsakov, M V; Ovsyannikov, A I; Popovich, I G; Napalkov, N P; Tomatis, L



Effects of maternally exposed coloring food additives on receptor expressions related to learning and memory in rats.  


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

Ceyhan, Betul Mermi; Gultekin, Fatih; Doguc, Duygu Kumbul; Kulac, Esin



Effect of exercise and protein intake during pregnancy on maternal and fetal zinc content in the Sprague-Dawley rat  

SciTech Connect

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.

Asente, R.A.; Cameron, S.R.; Taper, L.J.



Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval  

PubMed Central

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.

Bowers, J. Michael; Perez-Pouchoulen, Miguel; Edwards, N. Shalon; McCarthy, Margaret M.



Changes in Maternal liver Cyp2c and Cyp2d Expression and Activity During Rat Pregnancy  

PubMed Central

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.

Dickmann, Leslie J.; Tay, Suzanne; Senn, Tauri D.; Zhang, Huixia; Visone, Anthony; Unadkat, Jashvant D.; Hebert, Mary F.; Isoherranen, Nina



Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring.  


Titanium dioxide nanoparticles (TiO2-NPs) are massively produced in the environment, and because of their wide usage, they are a potential risk of damage to human health. TiO2-NPs are often used as additives for paints, papers, and foods. The central nervous system (CNS), including hippocampal regions, is potentially susceptible targets for TiO2-NPs. This study aimed to determine the effects of exposure to TiO2-NPs during pregnancy on hippocampal cell proliferation and the learning and memory of offspring. Pregnant Wistar rats received intragastric TiO2-NPs (100 mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21. Animals in the control group received the same volume of distilled water via gavage. After delivery, the one-day-old neonates were deeply anesthetized and weighed. They were then killed and the brains of each group were collected. Sections of the brains from the rat offspring were stained using Ki-67 immunolabeling and the immunohistochemistry technique. Some of the male offspring (n=12 for each group) were weaned at postnatal day (PND21), and housed until adulthood (PND60). Then the learning and memory in animals of each group were evaluated using passive avoidance and Morris water maze tests. The immunolabeling of Ki-67 protein as a proliferating cell marker showed that TiO2-NPs significantly reduced cell proliferation in the hippocampus of the offspring (P<0.05). Moreover, both the Morris water maze test and the passive avoidance test showed that exposure to TiO2-NPs significantly impaired learning and memory in offspring (P<0.05). These results may provide basic experimental evidence for a better understanding of the neurotoxic effects of TiO2-NPs on neonatal and adult brains. PMID:24577229

Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Motejaded, Fatemeh; Rafatpanah, Houshang; Zabihi, Hoda; Hosseini, Mahmoud; Bideskan, Alireza Ebrahimzadeh



Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.  


Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction. PMID:22365371

Aparicio, Michel; Bellizzi, Vincenzo; Chauveau, Philippe; Cupisti, Adamasco; Ecder, Tevfik; Fouque, Denis; Garneata, Liliana; Lin, Shanyan; Mitch, William E; Teplan, Vladimír; Zakar, Gábor; Yu, Xueqing



Developmental programming of neonatal pancreatic ?-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation.  


Maternal low-protein diets (LP) impair pancreatic ?-cell development, resulting in later-life failure and susceptibility to type 2 diabetes (T2D). We hypothesized that intrauterine and/or postnatal developmental programming seen in this situation involve altered ?-cell structure and relative time course of expression of genes critical to ?-cell differentiation and growth. Pregnant Wistar rats were fed either control (C) 20% or restricted (R) 6% protein diets during pregnancy (1st letter) and/or lactation (2nd letter) in four groups: CC, RR, RC, and CR. At postnatal days 7 and 21, we measured male offspring ?-cell fraction, mass, proliferation, aggregate number, and size as well as mRNA level for 13 key genes regulating ?-cell development and function in isolated islets. Compared with CC, pre- and postnatal LP (RR) decreased ?-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. LP only in pregnancy (RC) also decreased ?-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. Postnatal LP offspring (CR) showed decreased ?-cell mass but increased ?-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. We conclude that LP in pregnancy sets the trajectory of postnatal ?-cell growth and differentiation, whereas LP in lactation has smaller effects. We propose that LP promotes differentiation through upregulation of transcription factors that stimulate differentiation at the expense of proliferation. This results in a decreased ?-cell reserve, which can contribute to later-life predisposition to T2D. PMID:22436693

Rodríguez-Trejo, Adriana; Ortiz-López, María Guadalupe; Zambrano, Elena; Granados-Silvestre, María de Los Ángeles; Méndez, Carmen; Blondeau, Bertrand; Bréant, Bernadette; Nathanielsz, Peter W; Menjivar, Marta



Effects of an Early Experience of Reward through Maternal Contact or its Denial on Laterality of Protein Expression in the Developing Rat Hippocampus  

PubMed Central

Laterality is a basic characteristic of the brain which is detectable early in life. Although early experiences affect laterality of the mature brain, there are no reports on their immediate neurochemical effects during neonatal life, which could provide evidence as to the mechanisms leading to the lateralized brain. In order to address this issue, we determined the differential protein expression profile of the left and right hippocampus of 13-day-old rat control (CTR) pups, as well as following exposure to an early experience involving either receipt (RER) or denial (DER) of the expected reward of maternal contact. Proteomic analysis was performed by 2-dimensional polyacrylamide gel electrophoresis (PAGE) followed by mass spectroscopy. The majority of proteins found to be differentially expressed either between the three experimental groups (DER, RER, CTR) or between the left and right hemisphere were cytoskeletal (34%), enzymes of energy metabolism (32%), and heat shock proteins (17%). In all three groups more proteins were up-regulated in the left compared to the right hippocampus. Tubulins were found to be most often up-regulated, always in the left hippocampus. The differential expression of ?-tubulin, ?-actin, dihydropyrimidinase like protein 1, glial fibrillary acidic protein (GFAP) and Heat Shock protein 70 revealed by the proteomic analysis was in general confirmed by Western blots. Exposure to the early experience affected brain asymmetry: In the RER pups the ratio of proteins up-regulated in the left hippocampus to those in the right was 1.8, while the respective ratio was 3.6 in the CTR and 3.4 in the DER. Our results could contribute to the elucidation of the cellular mechanisms mediating the effects of early experiences on the vulnerability for psychopathology, since proteins shown in our study to be differentially expressed (e.g. tubulins, dihydropyrimidinase like proteins, 14-3-3 protein, GFAP, ATP synthase, ?-internexin) have also been identified in proteomic analyses of post-mortem brains from psychiatric patients.

Raftogianni, Androniki; Stamatakis, Antonios; Papadopoulou, Angeliki; Vougas, Konstantinos; Anagnostopoulos, Athanasios K.; Stylianopoulou, Fotini; Tsangaris, George Th.



Maternal "junk-food" feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.  


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: 16 ± 0.6 vs. 11 ± 0.8 g/kg/d; females: 19 ± 1.3 vs. 13 ± 0.4 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. PMID:21427213

Ong, Z Y; Muhlhausler, B S



Effect of maternal exposure of fluoride on biometals and oxidative stress parameters in developing CNS of rat.  


Excessive intake of essential elements agitates elemental homeostasis resulting in their heterogeneous distribution. Distraction of these elements in central nervous system (CNS) have been demonstrated in many neurological disorders, which are vital in generating free radicals, causing oxidative stress, and contributing to neuronal maladies. The developing CNS is highly vulnerable to environmental agents, including fluoride. Fluorosis is one such disorder ensued from excessive consumption of fluoride containing water and/or foods that poses a greater threat to the life. Present study offers perturbations caused by fluoride toxicity on the level of biometal and antioxidant homeostasis and their interactions. Pregnant Wistar rats were exposed to 100- and 200-ppm fluoride (F(-)) in drinking water and controls with tap water. The pups born to them were used for the study. On 21st postnatal day, the concentration of fluoride, biometals, and oxidative stress markers were determined in discrete regions of CNS. The levels of fluoride, copper, and iron increased whereas manganese and zinc were decreased considerably. Among antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase were decreased and lipid peroxidation was increased with regional alterations. The correlation coefficient values among oxidative stress markers and biometals were either positive or negative and showed less significance during correlation. The results confirm that the fluoride provoked oxidative stress and biometal deformations are synergistic that successively governs the neuronal damage and developing CNS no longer prevents exacerbations of fluoride. PMID:19495574

Narayanaswamy, Madhusudhan; Piler, Mahaboob Basha



Association between Maternal Serum Perfluoroalkyl Substances during Pregnancy and Maternal and Cord Thyroid Hormones: Taiwan Maternal and Infant Cohort Study.  


Background: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment.Objectives: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates.Methods: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models.Results: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3.Conclusions: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.Citation: Wang Y, Rogan WJ, Chen PC, Lien GW, Chen HY, Tseng YC, Longnecker MP, Wang SL. 2014. Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 122:529-534;? PMID:24577800

Wang, Yan; Rogan, Walter J; Chen, Pau-Chung; Lien, Guang-Wen; Chen, Hsiao-Yen; Tseng, Ying-Chih; Longnecker, Matthew P; Wang, Shu-Li



Association between Maternal Serum Perfluoroalkyl Substances during Pregnancy and Maternal and Cord Thyroid Hormones: Taiwan Maternal and Infant Cohort Study  

PubMed Central

Background: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. Objectives: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. Methods: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. Results: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: –0.028, –0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3. Conclusions: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses. Citation: Wang Y, Rogan WJ, Chen PC, Lien GW, Chen HY, Tseng YC, Longnecker MP, Wang SL. 2014. Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 122:529–534;?

Rogan, Walter J.; Chen, Pau-Chung; Lien, Guang-Wen; Chen, Hsiao-Yen; Tseng, Ying-Chih; Longnecker, Matthew P.



Impairment of Rat Fetal Beta-Cell Development by Maternal Exposure to Dexamethasone during Different Time-Windows  

PubMed Central

Aim Glucocorticoids (GCs) take part in the direct control of cell lineage during the late phase of pancreas development when endocrine and exocrine cell differentiation occurs. However, other tissues such as the vasculature exert a critical role before that phase. This study aims to investigate the consequences of overexposure to exogenous glucocorticoids during different time-windows of gestation for the development of the fetal endocrine pancreas. Methods Pregnant Wistar rats received dexamethasone acetate in their drinking water (1 µg/ml) during the last week or throughout gestation. Fetuses and their pancreases were analyzed at day 15 and 21 of gestation. Morphometrical analysis was performed on pancreatic sections after immunohistochemistry techniques and insulin secretion was evaluated on fetal islets collected in vitro. Results Dexamethasone given the last week or throughout gestation reduced the beta-cell mass in 21-day-old fetuses by respectively 18% or 62%. This was accompanied by a defect in insulin secretion. The alpha-cell mass was reduced similarly. Neither islet vascularization nor beta-cell proliferation was affected when dexamethasone was administered during the last week, which was however the case when given throughout gestation. When given from the beginning of gestation, dexamethasone reduced the number of cells expressing the early marker of endocrine lineage neurogenin-3 when analyzed at 15 days of fetal age. Conclusions GCs reduce the beta- and alpha-cell mass by different mechanisms according to the stage of development during which the treatment was applied. In fetuses exposed to glucocorticoids the last week of gestation only, beta-cell mass is reduced due to impairment of beta-cell commitment, whereas in fetuses exposed throughout gestation, islet vascularization and lower beta-cell proliferation are involved as well, amplifying the reduction of the endocrine mass.

Dumortier, Olivier; Theys, Nicolas; Ahn, Marie-Therese; Remacle, Claude; Reusens, Brigitte



Maternal cocaine administration causes an epigenetic modification of protein kinase Cepsilon gene expression in fetal rat heart.  


Protein kinase Cepsilon (PKCepsilon) plays a pivotal role in cardioprotection during cardiac ischemia and reperfusion injury. Recent studies demonstrated that prenatal cocaine exposure caused a decrease in PKCepsilon expression and increased heart susceptibility to ischemic injury in adult offspring, suggesting an in utero programming of PKCepsilon gene expression pattern in the heart. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for cocaine-mediated repression of the PKCepsilon gene in the heart. Pregnant rats were administered either saline or cocaine intraperitoneally (15 mg/kg) twice daily from days 15 to 20 of gestational age, and term fetal hearts were studied. Cocaine treatment significantly decreased PKCepsilon mRNA and protein levels in the heart. CpG dinucleotides found in cAMP response element-binding protein (CREB), CREB/c-Jun1, and CREB/c-Jun2 binding sites at the proximal promoter region of the PKCepsilon gene were densely methylated and were not affected by cocaine. In contrast, methylation of CpGs in the activator protein 1 (AP-1) binding sites was low but was significantly increased by cocaine. Reporter gene assays showed that the AP-1 binding site played a strong stimulatory role of PKCepsilon gene transcription. Methylation of the AP-1 binding sites significantly decreased AP-1 binding to the PKCepsilon promoter. Supershift analyses implicated c-Jun homodimers binding to the AP-1 binding sites. Cocaine did not affect nuclear c-Jun levels or the binding of c-Jun to the unmethylated AP-1 binding sites. The results indicate a role for DNA methylation in cocaine-mediated PKCepsilon gene repression in the developing heart and suggest an epigenetic mechanism affecting this gene linked with vulnerability of ischemic injury in the heart of adult offspring. PMID:17202284

Zhang, Haitao; Darwanto, Agus; Linkhart, Thomas A; Sowers, Lawrence C; Zhang, Lubo



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

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.

Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana



Comparison of maternal separation and early handling in terms of their neurobehavioral effects in aged rats 1 2 1 Present address: Max Planck Institute for Evolutionary Anthropology, Inselstr. 22, D-04103 Leipzig, Germany. 2 Present address: Janssen Research Foundation, Turnhoutseweg 30, B2340 Beerse Belgium  

Microsoft Academic Search

In the rat, relative to pup nonhandling (NH), early handling (EH) leads to old-adult offspring with a hyporesponsive HPA axis, superior spatial cognition, and greater hippocampal (HIPP) neuronal density. The present study compared the effects of EH and repeated maternal separation (MS), in the form of 6-hr separation on each of 4 days beginning at day 12, on spatial cognition,

Julia Lehmann; Christopher R. Pryce; Ana L. Jongen-Rêlo; Thomas Stöhr; Helen H. J. Pothuizen; Joram Feldon



Protein Nutrition of Southern Plains Small Mammals: Immune Response to Variation in Maternal and Offspring Dietary Nitrogen  

EPA Science Inventory

Maternal nutrition during pregnancy and postnatal offspring nutrition may influence offspring traits. We investigated the effects of maternal and postweaning offspring dietary nitrogen on immune function and hematology in two species of rodent: the hispid cotton rat (Sigmodon his...


Maternal exposure to the CB1 cannabinoid agonist WIN 55212-2 produces robust changes in motor function and intrinsic electrophysiological properties of cerebellar Purkinje neurons in rat offspring.  


The cerebellum, which controls coordinated and rapid movements, is a potential target for the deleterious effects of drugs of abuse including cannabis (i.e. marijuana, cannabinoids). Prenatal exposure to cannabinoids has been documented to cause abnormalities in motor and cognitive development, but the exact mechanism of this effect at the cellular level has not been fully elucidated. Previous studies indicate that cannabinoids are capable of modulating synaptic neurotransmission. In addition to altering synaptic activity, cannabinoid exposure may also change intrinsic neuronal properties. In the present study several different approaches including behavioral assays, extracellular field potential recordings and whole-cell patch clamp recordings, were used to address whether maternal exposure to the CB1 cannabinoid receptor agonist WIN 55-212-2 (WIN) affects the intrinsic electrophysiological properties of Purkinje neurons. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency, total distance moved and mobility of the offspring, but significantly increased the time of the righting reflex, the grooming frequency and immobility. Neuromotor function, as assessed in the grip test and balance beam test, was also significantly impaired in prenatally WIN-treated group. Prenatal exposure to WIN increased the amplitude of population spikes (PS) recorded from the cerebellar Purkinje cell layer of offspring following synaptic blockage. WIN treatment of pregnant rats also profoundly affected the intrinsic properties of Purkinje neurons in offspring. This treatment increased the firing regularity, firing frequency, amplitude of afterhyperpolarization (AHP), the peak amplitude of action potential and the first spike latency, but decreased significantly the time to peak and duration of action potentials, the instantaneous firing frequency, the rate of rebound action potential and the voltage "sag" ratio. These results raise the possibility that maternal exposure to cannabinoids may profoundly affect the intrinsic membrane properties of cerebellar Purkinje neurons of offspring by altering the membrane excitability through modulation of intrinsic ion channels. PMID:20969930

Shabani, M; Hosseinmardi, N; Haghani, M; Shaibani, V; Janahmadi, M



Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high-fat diet of the young to facilitate the onset of metabolic disorders in rat offspring.  


Obesity and non-alcoholic fatty liver disease are the most common metabolic disorders in society today. Previously, we found that supplementing the maternal diet during pregnancy with chocolate and fructose has negative effects on the well-being of the offspring that were ameliorated if the offspring were fed a normal diet during postnatal life. In the present study, we investigated whether feeding offspring a high-fat diet would augment the maternal programming effects and whether extra protein supply can correct the low birth weight resulting from the chocolate-supplemented maternal diet. Pregnant Sprague-Dawley rats were divided into three groups and fed either standard chow (normal nutrition; NN), chocolate- and fructose-supplemented standard chow with casein sodium (overnutrition; ON) or the supplemented standard chow without casein sodium (malnutrition; MN) throughout pregnancy. Male offspring were weaned on either standard or high-fat chow. Dams in the MN group exhibited moderate weight gain, consumed 50% less protein (P < 0.001) but more carbohydrates during gestation and delivered pups with a 12% lower birth weight (P < 0.05) than pups in the NN group, results that are consistent with previous findings. When fed on a high-fat diet after birth, pups from dams in the MN group (MNHD) had 30% more body fat (P = 0.023) and liver triglyceride (TG) levels that were double (P < 0.01) those in offspring in the other groups, leading to fatty livers in these offspring at 14 weeks of age. Hepatic expression of the PPAR?, ApoB100, MTTP, CPT1 and SREBP1c genes was significantly downregulated in the MNHD group (P < 0.05 for all), indicating changes in lipid metabolism. Although dams in the ON group exhibited marked gestational weight gain (P < 0.01), they gave birth to normal weight pups that only manifested mild increases in body fat and liver TG content (P < 0.05), without significant changes in the expression of most genes when fed with the high-fat diet. The results suggest that the extra protein supply in the form of casein sodium was able to correct some negative programming effects of the chocolate and fructose supplementation of the maternal diet, which, in conjunction with a high-fat diet in the offspring, may facilitate the onset of metabolic disorders, with impaired liver gene expression possibly a key contributor. PMID:23819696

Zhang, Zhi-Yun; Dai, Yun-Bin; Wang, Hao-Nan; Wang, Ming-Wei



Maternal administration of betamethasone inhibits proliferation induced by fetal tracheal occlusion in the nitrofen rat model for congenital diaphragmatic hernia: a placebo-controlled study  

Microsoft Academic Search

Purpose  Fetal tracheal occlusion (TO) is offered to fetuses with severe pulmonary hypoplasia due to congenital diaphragmatic hernia\\u000a (CDH). TO induces lung growth, but even when performed minimally invasive, there is a risk for iatrogenic preterm delivery.\\u000a Whenever this is anticipated, maternal glucocorticoids (GC) may be given to enhance lung maturation. The pulmonary effects\\u000a of GC in fetuses with CDH that

Steffi Mayer; Philipp Klaritsch; Lourenço Sbragia; Jaan Toelen; Holger Till; Jan A. Deprest



A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats.  


The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood. PMID:23561448

Hallam, Megan C; Reimer, Raylene A



Near miss maternal morbidity.  


Audit of severe maternal morbidity is a potent tool in determining standards of maternity care. This study determines the incidence of severe acute maternal morbidity in our population, identifies the underlying organ dysfunction and associated obstetric risk factors, and compares them to published international reports. Over a 5 year period, 1999-2003, data were collected prospectively from patients with severe acute maternal morbidity. There were 36,802 women who delivered infants weighing more than 500 g over the 5 years with 53 cases of severe maternal morbidity. There were two indirect maternal deaths yielding an incidence of 1.4/1000 for severe maternal morbidity and 5.4/100,000 for maternal mortality. The severe maternal morbidity to mortality ratio was 26.5:1. Massive obstetric haemorrhage requiring acute blood transfusion of > or = 5 units of packed red cells occurred in 77% of cases. This study identifies the feasibility of audit of severe maternal morbidity using simple defined clinical criteria. The incidence and underlying aetiology of severe maternal morbidity in our unit is comparable to other developed countries. It is essential that data on severe maternal morbidity are reviewed and analysed continuously at local hospital and national level to assess, maintain and improve clinical standards. PMID:18624257

Lynch, C M; Sheridan, C; Breathnach, F M; Said, S; Daly, S; Byrne, B



Dibutyl Phthalate: Maternal Effects versus Fetotoxicity (Journal Version),  

National Technical Information Service (NTIS)

Dibutyl phthalate, a plasticizer, is a teratogen in mice and rabbits but produces fetal loss in the rat. Long-term dosing studies indicating reduced fertility in the rat suggested a maternal effect of the compound. The decidual cell response (DCR) and pre...

A. M. Cummings L. E. Gray



The regulation of hepatic Pon1 by a maternal high-fat diet is gender specific and may occur through promoter histone modifications in neonatal rats.  


The antioxidant (AOX) defense system is critical for combating whole-body oxidative stress, and the present study aimed to determine the consequences of a maternal high-fat (HF) diet on neonatal hepatic lipid accumulation, oxidative stress, the expression of AOX genes, as well as epigenetic histone modifications within Pon1, an AOX enzyme. Hepatic thiobarbituric acid reactive substances were significantly increased and nonesterified fatty acids decreased in offspring of HF-fed dams, while triglycerides increased in male but not female HF offspring when compared to controls (C). Pon1, Pon2, Pon3 and Sod2 were significantly increased in offspring of HF-fed dams when compared to C. However, the increase in Pon1 and Pon3 was only significant in male but not female offspring. When compared to C, the hepatic Pon1 promoter of male and female HF offspring had significantly more acetylated histone H4 as well as dimethylated histone H3 at lysine residue 4, which are both involved in transcriptional activation. Trimethylation of histone H3 at lysine residue 9, which is involved in transcriptional repression, was only associated with genes in females. Results from the present study reveal that a maternal HF diet affects hepatic metabolism in the neonate in a gender-specific manner, and these differences, in association with epigenetic modification of histones, may contribute to the known gender differences in oxidative balance. PMID:24445041

Strakovsky, Rita S; Zhang, Xiyuan; Zhou, Dan; Pan, Yuan-Xiang



Toxicity study of maternal transfer of polychlorinated biphenyls and diethyl phthalate to 21-day-old male and female weanling pups of Wistar rats  

Microsoft Academic Search

Polychlorinated biphenyls (PCBs) are environmental pollutants known to act as xenoestrogens. PCBs and diethylphthalate (DEP) are ubiquitous environmental pollutants because both are used as plasticizers and in various other industrial applications. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP and PCB in 21-day-old male and female pups of Wistar rats. Healthy young male and female albino

Contzen Pereira; C. Vaman Rao



Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II-the developmental pattern of neurons in relation to oxidative stress and antioxidant defense system.  


Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50--200 T4 ?g/kg body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in its density and complexity with age progress. This development may depend, largely, on THs state. Both maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant enzymes, four non-enzymatic antioxidants and one oxidative stress marker (lipid peroxidation, LPO) followed a synchronized course of alterations in cerebrum, cerebellum and medulla oblongata. In both thyroid states, the oxidative damage has been demonstrated by the increased LPO and inhibition of enzymatic and non-enzymatic antioxidants in most examined ages and brain regions. These disturbances in the antioxidant defense system led to deterioration in the neuronal maturation and development. In conclusion, it can be suggested that the maldevelopment of neurons and dendrites in different brain regions of offspring of hypothyroid and hyperthyroid mother rat dams may be attributed, at least in part, to the excess oxidative stress and deteriorated antioxidant defense system in such conditions. PMID:22664656

Ahmed, O M; Ahmed, R G; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M



Fetal and maternal brain and plasma levels of cocaine and benzoylecgonine following chronic subcutaneous administration of cocaine during gestation in rats  

Microsoft Academic Search

The distribution of cocaine and the cocaine metabolite benzoylecgonine (BE) in brain and plasma of Sprague-Dawley rat dams and their near-term fetuses was assessed 0.5 and 2 h post-injection on gestational day 20 following chronic daily subcutaneous injections of 10, 20, or 40 mg\\/kg\\/3 ml cocaine hydrochloride beginning on gestational day 8. Plasma concentrations of cocaine reached in the dams

Linda Patia Spear; Nancy A. Frambes; Cheryl L. Kirstein



Increased Maternal Corticosterone Levels in Rats: Effects on Brain 5HT1A Receptors and Behavioral Coping With Stress in Adult Offspring  

Microsoft Academic Search

This study examined the consequences of elevated corticosterone levels in lactating rats on their offspring's serotonergic 5-hydroxytryptamine (5-HT)1A receptor system and behavioral coping with stress. The mothers received normal drinking water or water with corticosterone, which, via the milk, enters the circulation and brains of the pups. In adulthood, the corticosterone-nursed offspring showed a consistently more passive way of coping

Peter Meerlo; Katalin M. Horvath; Paul G. M. Luiten; Luciano Angelucci; Assia Catalani; Jaap M. Koolhaas



Interpretation of analysis of variance models using principal component analysis to assess the effect of a maternal anticancer treatment on the mineralization of rat bones.  


The goal of the present study is to assess the effects of anticancer treatment with cyclophosphamide and cytarabine during pregnancy on the mineralization of mandible bones in 7-, 14- and 28-day-old rats. Each bone sample was described by its X-ray fluorescence spectrum characterizing the mineral composition. The data collected are multivariate in nature and their structure is difficult to visualize and interpret directly. Therefore, methods like analysis of variance-principal component analysis (ANOVA-PCA) and ANOVA-simultaneous component analysis (ASCA), which are suitable for the analysis of highly correlated spectral data and are able to incorporate information about the underlined experimental design, are greatly valued. In this study, the ASCA methodology adapted for unbalanced data was used to investigate the impact of the anticancer drug treatment during pregnancy on the mineralization of the mandible bones of newborn rats and to examine any changes in the mineralization of the bones over time. The results showed that treatment with cyclophosphamide and cytarabine during pregnancy induces a decrease in the K and Zn levels in the mandible bones of newborns. This suppresses the development of mandible bones in rats in the early stages (up to 14 days) of formation. An interesting observation was that the levels of essential minerals like K, Mg, Na and Ca vary considerably in the different regions of the mandible bones. PMID:21338749

Stanimirova, I; Michalik, K; Drzazga, Z; Trzeciak, H; Wentzell, P D; Walczak, B



Maternal health outcomes in Europe  

Microsoft Academic Search

Objectives: To use PERISTAT data on indicators of maternal mortality and morbidity to explore maternal health outcomes in Europe, and to discuss the implications of variations in the data sources for these indicators. Study design: The PERISTAT feasibility study provides the source for this descriptive study, covering 15 European countries. Maternal mortality ratios are calculated, and data to describe maternal

Sophie Alexander; Katherine Wildman; Weihong Zhang; Martin Langer; Christian Vutuc; Gunilla Lindmarke


Maternal exposure to anti-androgenic compounds, vinclozolin, flutamide and procymidone, has no effects on spermatogenesis and DNA methylation in male rats of subsequent generations  

SciTech Connect

To verify whether anti-androgens cause transgenerational effects on spermatogenesis and DNA methylation in rats, gravid Crl:CD(SD) female rats (4 or 5/group, gestational day (GD) 0 = day sperm detected) were intraperitoneally treated with anti-androgenic compounds, such as vinclozolin (100 mg/kg/day), procymidone (100 mg/kg/day), or flutamide (10 mg/kg/day), from GD 8 to GD 15. Testes were collected from F1 male pups at postnatal day (PND) 6 for DNA methylation analysis of the region (210 bp including 7 CpG sites) within the lysophospholipase gene by bisulfite DNA sequencing method. F0 and F1 males underwent the sperm analysis (count, motility and morphology), followed by DNA methylation analysis of the sperm. Remaining F1 males were cohabited with untreated-females to obtain F2 male pups for subsequent DNA methylation analysis of the testes at PND 6. These analyses showed no effects on spermatogenesis and fertility in F1 males of any treatment group. DNA methylation status in testes (F1 and F2 pups at PND 6) or sperms (F1 males at 13 weeks old) of the treatment groups were comparable to the control at all observation points, although DNA methylation rates in testes were slightly lower than those in sperm. In F0 males, no abnormalities in the spermatogenesis, fertility and DNA methylation status of sperm were observed. No transgenerational abnormalities of spermatogenesis and DNA methylation status caused by anti-androgenic compounds were observed.

Inawaka, Kunifumi [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka (Japan)], E-mail:; Kawabe, Mayumi [Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); DIMS Institute of Medical Science, Inc., Ichinomiya (Japan); Takahashi, Satoru [Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Doi, Yuko [Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); DIMS Institute of Medical Science, Inc., Ichinomiya (Japan); Tomigahara, Yoshitaka [Corporate Planning and Coordination Office, Sumitomo Chemical Co., Ltd., Tokyo (Japan); Tarui, Hirokazu; Abe, Jun; Kawamura, Satoshi [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka (Japan); Shirai, Tomoyuki [Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)



Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine.  


When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained. Glycine may become conditionally essential, as its rate of endogenous formation is inadequate to meet metabolic needs, and may be limiting for the normal development of the fetus. In the present study, five groups of Wistar rats were provided during pregnancy with one of five diets: a control diet containing 18% (w/w) casein (CON), a low-protein diet containing 9% casein (MLP), or the low-protein diet supplemented with 3% glycine (MLPG), alanine (MLPA) or urea (MLPU). The offspring were weaned on to standard laboratory chow, and blood pressure was measured at 4 weeks of age. Blood pressure was significantly increased in the MLP, MLPA and MLPU groups compared with the CON group, but for the MLPG group blood pressure was not significantly different from CON. Compared with the CON group, body weight was significantly reduced for the MLP, MLPA and MLPG groups, but for the MLPU group body weight was not different from CON. These data show that different forms of non-essential dietary nitrogen, when consumed during pregnancy, exert different effects upon the growth and function of the offspring. The availability of glycine appears to be of critical importance for normal cardiovascular development. PMID:12444916

Jackson, Alan A; Dunn, Rebecca L; Marchand, Michael C; Langley-Evans, Simon C



Maternal regulation of infant brain state.  


Patterns of neural activity are critical for sculpting the immature brain, and disrupting this activity is believed to underlie neurodevelopmental disorders [1-3]. Neural circuits undergo extensive activity-dependent postnatal structural and functional changes [4-6]. The different forms of neural plasticity [7-9] underlying these changes have been linked to specific patterns of spatiotemporal activity. Since maternal behavior is the mammalian infant's major source of sensory-driven environmental stimulation and the quality of this care can dramatically affect neurobehavioral development [10], we explored, for the first time, whether infant cortical activity is influenced directly by interactions with the mother within the natural nest environment. We recorded spontaneous neocortical local field potentials in freely behaving infant rats during natural interactions with their mother on postnatal days ?12-19. We showed that maternal absence from the nest increased cortical desynchrony. Further isolating the pup by removing littermates induced further desynchronization. The mother's return to the nest reduced this desynchrony, and nipple attachment induced a further reduction but increased slow-wave activity. However, maternal simulation of pups (e.g., grooming and milk ejection) consistently produced rapid, transient cortical desynchrony. The magnitude of these maternal effects decreased with age. Finally, systemic blockade of noradrenergic beta receptors led to reduced maternal regulation of infant cortical activity. Our results demonstrate that during early development, mother-infant interactions can immediately affect infant brain activity, in part via a noradrenergic mechanism, suggesting a powerful influence of the maternal behavior and presence on circuit development. PMID:24980504

Sarro, Emma C; Wilson, Donald A; Sullivan, Regina M



Transgenerational Effects of Social Environment on Variations in Maternal Care and Behavioral Response to Novelty  

Microsoft Academic Search

Cross-fostering studies in the rat have illustrated the importance of the postnatal environment in mediating the transmission of maternal licking\\/grooming (LG) from mother to offspring. The authors addressed the question of how postweaning social conditions can alter the patterns of maternal behavior. Juvenile female offspring of high LG and low LG mothers were placed in either standard, enriched, or impoverished

Frances A. Champagne; Michael J. Meaney



[Maternal death: unequal risks].  


Nearly 99% of maternal deaths in the world each year occur in developing countries. New efforts have recently been undertaken to combat maternal mortality through research and action. The medical causes of such deaths are coming to be better understood, but the social mechanisms remain poorly grasped. Maternal mortality rates in developing countries are difficult to interpret because they tend to exclude all deaths not occurring in health care facilities. The countries of Europe and North America have an average maternal mortality rate of 30/100,000 live births, representing about 6000 deaths each year. The developing countries of Asia, Africa, and Latin America have rates of 270-640/100,000, representing some 492,000 deaths annually. For a true comparison of the risks of maternal mortality in different countries, the risk itself and the average number of children per woman must both be considered. A Nigerian woman has 375 times greater risk of maternal death than a Swedish woman, but since she has about 4 times more children, her lifetime risk of maternal death is over 1500 times greater than that of the Swedish woman. The principal medical causes of maternal death are known: hemorrhages due to placenta previa or retroplacental hematoma, mechanical dystocias responsible for uterine rupture, toxemia with eclampsia, septicemia, and malaria. The exact weight of abortion in maternal mortality is not known but is probably large. The possible measures for improving such rates are of 3 types: control of fertility to avoid early, late, or closely spaced pregnancies; effective medical surveillance of the pregnancy to reduce the risk of malaria, toxemia, and hemorrhage, and delivery in an obstetrical facility, especially for high-risk pregnancies. Differential access to high quality health care explains much of the difference between mortality rates in urban and rural, wealthy and impoverished areas of the same country. The social determinants of high maternal mortality rates include political, geographic, and economic mechanisms of exclusion which affect the vast majority of the population in developing countries. Political power is concentrated in the hands of relatively small groups whose decisions about such expenditures as health care are usually more favorable to the privileged. A consequence of the very unequal regional development in most Third World countries is that health, educational, and most other resources are concentrated in large cities and perhaps 1 or 2 strategic regions, leaving most of the population underserved. The low social position of women leaves them doubly vulnerable. The social factors adding to risks of maternal mortality should be considered in programs of prevention if the causes and not just the consequences are to be addressed. PMID:12281979

Defossez, A C; Fassin, D



Effects of an early experience of reward through maternal contact or its denial on the dopaminergic system of the rat brain.  


The mesolimbic/mesocortical dopaminergic pathway plays a pivotal role in the reward system. During the neonatal period the mother is the main source of rewarding stimuli. We have developed an experimental model in which rat pups learn a T-maze during the neonatal period (postnatal day (PND) 10-13) using contact with the mother as the reward. One group of animals is allowed contact with the mother (receipt of expected reward, RER) while the other was denied (denial of expected reward, DER). We determined the effects of these two early experiences in the prefrontal cortex (PFC) and the nucleus accumbens (nAc), the levels of dopamine (DA) and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] by high-performance liquid chromatography and those of D1 and D2 receptors by autoradiographic in vitro binding both on PND 13 and in adulthood. On PND13, 2h after the end of training, the RER experience resulted in higher DA, HVA and D1 receptor levels in the nAc, while the DER in lower DA and its metabolites (DOPAC and HVA) in the PFC. These results could be related to the reward the RER pups received through the contact with their mother. The RER and DER early experience had long-term sex-dependent effects: The RER-induced activation of the dopaminergic system in the nAc was also evident in adult female rats. In contrast, adult DER males, similar to PND13 animals, had reduced dopamine in the PFC. Our results document that early experiences, a key determinant of adult brain function, affect the dopaminergic system which is disturbed in many psychiatric diseases. PMID:24680882

Raftogianni, A; Stamatakis, A; Diamantopoulou, A; Kollia, A-M; Stylianopoulou, F



Maternal thimerosal exposure results in aberrant cerebellar oxidative stress, thyroid hormone metabolism, and motor behavior in rat pups; sex- and strain-dependent effects.  


Methylmercury (Met-Hg) and ethylmercury (Et-Hg) are powerful toxicants with a range of harmful neurological effects in humans and animals. While Met-Hg is a recognized trigger of oxidative stress and an endocrine disruptor impacting neurodevelopment, the developmental neurotoxicity of Et-Hg, a metabolite of thimerosal (TM), has not been explored. We hypothesized that TM exposure during the perinatal period impairs central nervous system development, and specifically the cerebellum, by the mechanism involving oxidative stress. To test this, spontaneously hypertensive rats (SHR) or Sprague-Dawley (SD) rat dams were exposed to TM (200 ?g/kg body weight) during pregnancy (G10-G15) and lactation (P5-P10). Male and female neonates were evaluated for auditory and motor function; cerebella were analyzed for oxidative stress and thyroid metabolism. TM exposure resulted in a delayed startle response in SD neonates and decreased motor learning in SHR male (22.6%), in SD male (29.8%), and in SD female (55.0%) neonates. TM exposure also resulted in a significant increase in cerebellar levels of the oxidative stress marker 3-nitrotyrosine in SHR female (35.1%) and SD male (14.0%) neonates. The activity of cerebellar type 2 deiodinase, responsible for local intra-brain conversion of thyroxine to the active hormone, 3',3,5-triiodothyronine (T3), was significantly decreased in TM-exposed SHR male (60.9%) pups. This coincided with an increased (47.0%) expression of a gene negatively regulated by T3, Odf4 suggesting local intracerebellar T3 deficiency. Our data thus demonstrate a negative neurodevelopmental impact of perinatal TM exposure which appears to be both strain- and sex-dependent. PMID:22015705

Sulkowski, Z L; Chen, T; Midha, S; Zavacki, A M; Sajdel-Sulkowska, Elizabeth M



Impaired myocardial performance in a normotensive rat model of intrauterine growth restriction.  


Background:Intrauterine growth restriction (IUGR) is an important risk factor for cardiovascular disease. Previous studies revealed altered myocardial matrix composition after IUGR. We hypothesized that IUGR is accompanied by compromised myocardial performance independently from arterial hypertension.Methods:IUGR was induced in Wistar rats by maternal protein restriction, and hearts of male offspring were studied using echocardiography, immunohistochemistry, real-time PCR, and western blot analysis.Results:At day 70 of life, in the absence of arterial hypertension (mean arterial blood pressure: 101.3?±?7.1?mmHg in IUGR vs. 105.3?±?4.6?mmHg in controls, not significant (NS)), echocardiography showed a reduced contractility (ejection fraction: 65.4?±?1.8% in IUGR vs. 82.2?±?1.5% in controls, P < 0.001) of a more distensible myocardium in IUGR rats. Altered expression patterns of myosin chains and titin isoforms and increased expression levels of atrial natriuretic peptide, Na/K-ATPase, and ?-adrenergic receptor 1 were detected. A higher number of cardiac fibroblasts and vascular cross-sections were observed in IUGR rats, accompanied by elevated expression of hypoxia inducible factor 1 target genes, such as vascular endothelial growth factor and its receptors.Conclusion:We observed a blood pressure-independent impairment of myocardial function after IUGR, which possibly favors cardiovascular disease later in life. Some IUGR-induced myocardial changes (e.g., sarcomeric components) may partly explain the compromised cardiac performance, whereas others (e.g., elevated vascular supply) reflect compensatory mechanisms. PMID:24603294

Menendez-Castro, Carlos; Toka, Okan; Fahlbusch, Fabian; Cordasic, Nada; Wachtveitl, Rainer; Hilgers, Karl F; Rascher, Wolfgang; Hartner, Andrea



Effect of insulin and dexamethasone on fetal assimilation of maternal glucose.  


The growing fetus depends upon transfer of glucose from maternal blood to fetal tissues. Insulin and glucocorticoid impact maternal glucose metabolism, but the effects of these hormones on fetal glucose assimilation in vivo are understudied. We thus used positron emission tomography imaging to determine the disposition of [(18)F]fluorodeoxyglucose (FDG) in rats on gestational d 20, quantifying the kinetic competition of maternal tissues and fetus for glucose. Three fasting maternal states were studied: after 2-d dexamethasone (DEX), during euglycemic hyperinsulinemic clamp insulin receiving (INS), and control (CON). In CON and DEX mothers, FDG accumulation in fetuses and placentae was substantial, rivaling that of maternal brain. By contrast, FDG accumulation was reduced in INS fetuses, placentae, and maternal brain by approximately 2-fold, despite no diminution in FDG extraction kinetics from maternal blood into these structures. The reduced FDG accumulation was due to more rapid clearance of FDG from the circulation in INS mothers, related to increased FDG avidity in INS select maternal tissues, including skeletal muscle, brown adipose tissue, and heart. DEX treatment of mothers reduced fetal weight by nearly 10%. Nonetheless, the accumulation of FDG into placentae and fetuses was similar in DEX and CON mothers. In our rat model, fetal growth restriction induced by DEX does not involve diminished glucose transport to the fetus. Maternal insulin action has little effect on the inherent avidity of the fetal-placental unit for glucose but increases glucose utilization by maternal tissues, thus indirectly reducing the glucose available to the fetus. PMID:21084442

Norris, Andrew W; Wang, Chunlin; Yao, Jianrong; Walsh, Susan A; Sawatzke, Alexander B; Hu, Shanming; Sunderland, John J; Segar, Jeffrey L; Ponto, Laura L B



Maternal-Fetal Pharmacokinetics of Methanol. (Includes the Commentary of the Institute's Health Review Committee).  

National Technical Information Service (NTIS)

This study defines the physiological factors that govern methanol delivery to the developing fetus after maternal methanol exposure. The disposition of methanol after oral or intravenous administration was similar in pregnant and nonpregnant rats, regardl...

G. M. Pollack K. L. R. Brouwer



Effects of Intake of Maternal Dietary Elaidic Acids during Pregnancy and Lactation on the Fatty Acid Composition of Plasma, Erythrocyte Membrane, and Brain in Rat Pups  

PubMed Central

To investigate the effects of a dam's dietary elaidic acid (EA) intake during pregnancy and lactation on the fatty acid composition of plasma, erythrocyte membrane, and brain in rat pups, we fed two groups of dams either a soybean oil diet (SOD) or a shortening diet (SHD) containing soybean oil (10%) or shortening (10%), respectively. Although EA was not detected in the SOD, EA accounted for 25.3% of all fatty acid content in the SHD. On day 8 after birth, the EA levels in the stomach, plasma, and erythrocyte membrane of pups nursed by the dams fed the SHD were 11.6 ± 1.03%, 7.18 ± 1.20%, and 5.82 ± 1.00%, respectively. Although on day 8 after birth the EA level of the brains of pups nursed by SHD-fed dams was 0.56 ± 0.24%, EA was not detected on day 21 or day 82 after birth. These results suggest that EA intake during pregnancy and lactation supplies EA to plasma, remains in the erythrocyte membrane of pups, and moves into the brain in early infancy.

Eda, Ayumi; Kameoka, Rie; Nakashima, Yoko



Various Dietary Protein Intakes and Progression of Renal Failure in Spontaneously Hypercholesterolemic Imai Rats  

Microsoft Academic Search

Background\\/Aim: Dietary protein restriction is known to be beneficial in the preservation of the renal function in patients with chronic renal failure. Recently, the effect of varying quantity and quality of dietary protein intakes was also studied. This study investigates the effects of different dietary animal proteins on renal function in spontaneously hypercholesterolemic Imai rats that exhibit renal lesions similar

Xiang-Ming Liang; Haruhisa Otani; Qin Zhou; Yoshinori Tone; Ryoichi Fujii; Masatoshi Mune; Susumu Yukawa; Tadao Akizawa



Maternal behavior and developmental psychopathology  

Microsoft Academic Search

This paper reviews recent developments in the phenomenology, neurobiology, and genetics of maternal behavior in animal model systems from an evolutionary perspective on psychopathology. Following a review of the phenomenology and neurobiology of maternal behavior, recent studies addressing the role of genetic factors in the maternal behavior of rodents were identified in a search of literature in peer-reviewed journals. Gene

James F. Leckman; Amy E. Herman



Maternal correlates of maternal child feeding practices: a systematic review.  


Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation. PMID:22973806

McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena



Maternal sexuality and breastfeeding  

Microsoft Academic Search

In this paper I consider the ways in which lactation has been discussed as a form of maternal sexuality, and the implications this carries for our understanding of breastfeeding practices and sexuality. Drawing on knowledge constructed in the western world during the last half of the twentieth century, the paper identifies a shift between the radical ideologies of the 1960s

Alison Bartlett



Maternal serum screening.  

PubMed Central

Maternal serum screening (MSS) measures three serum markers: alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol, from which the risk of fetal Down syndrome or open neural tube defect is calculated. Initially, 8% of women will have positive results. I present a protocol for investigating these women. Family physicians should be informed about MSS so they can give their patients information and guidance.

Carroll, J. C.



Temperament and Maternal Employment.  

ERIC Educational Resources Information Center

Discusses a model of the bi-directional relations between children and the context of their living situations and explains how the usefulness of this model may be evaluated by assessing the relations between child temperament and maternal attitudes and behaviors. Also indicates how the child's temperament may influence the mother's decision to…

Lerner, Jacqueline V.; Galambos, Nancy L.



Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network  

PubMed Central

Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.

Motta, Simone C.; Guimaraes, Cibele Carla; Furigo, Isadora Clivatti; Sukikara, Marcia Harumi; Baldo, Marcus V. C.; Lonstein, Joseph S.; Canteras, Newton S.



Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors  

PubMed Central

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation.

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.



Maternal stress and high-fat diet effect on maternal behavior, milk composition, and pup ingestive behavior  

PubMed Central

Chronic variable prenatal stress or maternal high-fat diet results in offspring that are significantly heavier by the end of the first postnatal week with increased adiposity by weaning. It is unclear, however, what role maternal care and diet play in the ontogenesis of this phenotype and what contributions come from differences already established in the rat pups. In the present studies, we examined maternal behavior and milk composition as well as offspring ingestive behavior. Our aim was to better understand the development of the obese phenotype in offspring from dams subjected to prenatal stress and/or fed a high-fat (HF) diet during gestation and lactation. We found that dams maintained on a HF diet through gestation and lactation spent significantly more time nursing their pups during the first postnatal week. In addition, offspring of prenatal stress dams consumed more milk at postnatal day (PND) 3 and offspring of HF dams consume more milk on PND 7 in an independent ingestion test. Milk from HF dams showed a significant increase in fat content from PND 10-21. Together these results suggest that gestational dietary or stress manipulations can alter the rat offspring's developmental environment, evidence of which is apparent by PND 3. Alterations in maternal care, milk composition, and pup consumption during the early postnatal period may contribute to long-term changes in body weight and adiposity induced by maternal prenatal stress or high-fat diet.

Purcell, Ryan H.; Sun, Bo; Pass, Lauren L.; Power, Michael L.; Moran, Timothy H.; Tamashiro, Kellie L. K.



Psychological stressors as a model of maternal adversity: diurnal modulation of corticosterone responses and changes in maternal behavior.  


Maternal adversity is associated with long-lasting consequences on cognitive development, behavior and physiological responses in rat offspring. Few studies have examined whether repeated maternal stress produces repeated activation of the hypothalamus-pituitary-adrenal (HPA) axis in mothers and whether it modifies maternal behavior. Here, we tested a novel model of perinatal stress using repeated exposure to "purely" psychological stressors throughout the gestation and lactation periods in rats. We first tested the diurnal influences of repeated 1-h strobe light exposure on maternal corticosterone secretion. Despite the hyporesponsiveness to stress documented in late pregnant and lactating mothers, we observed an enhanced response to strobe light in the afternoon compared to the morning in stressed mothers during lactation. Next, dams were exposed to 24-h forced foraging followed by 10-h wet bedding during the diurnal peak of corticosterone secretion. Although no corticosterone responses to forced foraging and wet bedding were observed, the combination of both stressors had a significant effect on maternal behavior. Mother-pup interactions were significantly altered during the first 8 days of lactation. Taken together, these findings suggest that lactating mothers maintain responsiveness to specific and repeated psychological stressors, in particular at the time of the diurnal peak in corticosterone secretion. Depending on the stressor applied, either neuroendocrine activation or changes in maternal behavior might be important determinants of the long-term consequences in the offspring. The combination of forced foraging, wet bedding and strobe light might represent a novel model of mild maternal adversity using "purely" psychological stressors. PMID:17034794

Léonhardt, Marion; Matthews, Stephen G; Meaney, Michael J; Walker, Claire-Dominique



Maternal Health and HIV  

Microsoft Academic Search

The HIV\\/AIDS epidemic is one of the major factors affecting women's health, with 20 million women living with HIV and more than two million pregnancies in HIV-positive women each year. Most HIV infections in women are in resource-constrained settings where the risk of maternal morbidity and mortality is also unacceptably high, and where most of the 529,000 deaths from complications

James McIntyre



Maternal nodal and zebrafish embryogenesis.  


In fish and amphibians, the dorsal axis is specified by the asymmetric localization of maternally provided components of the Wnt signalling pathway. Gore et al. suggest that the Nodal signal Squint (Sqt) is required as a maternally provided dorsal determinant in zebrafish. Here we test their proposal and show that the maternal activities of sqt and the related Nodal gene cyclops (cyc) are not required for dorsoventral patterning. PMID:17994032

Bennett, James T; Stickney, Heather L; Choi, Wen-Yee; Ciruna, Brian; Talbot, William S; Schier, Alexander F



Translational control of maternal RNAs  

Microsoft Academic Search

Early development of many species depends on the temporal and spatial control of maternal gene products. This review discusses the control of maternal mRNAs that encode regulators of C. elegans embryogenesis. In the C. elegans embryo, maternal mRNA regulation is crucial to the patterning of early cell fates. Translational control of key mRNAs spatially organizes cell signaling pathways, localizes transcription

Thomas C. Evans; Craig P. Hunter



Adolescent maternal mortality in mozambique  

Microsoft Academic Search

Purpose: To describe adolescent maternal mortality and analyze its avoidability.Methods: An audit approach was used to clarify the presence of avoidable factors in 239 maternal deaths, of which 22% were among adolescents.Results: The main causes of adolescent death were malaria, pregnancy-induced hypertension, puerperal sepsis, and septic abortion. The audit classified as avoidable 75% of all maternal deaths.Conclusion: Adequate strategies addressing

Ana Carla L Granja; Fernanda Machungo; Aurelio Gomes; Staffan Bergström



Maternal diabetes affects specific extracellular matrix components during placentation  

PubMed Central

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg?1 i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal–fetal interface, leading to developmental abnormalities in the offspring.

Giachini, F R C; Carriel, V; Capelo, L P; Tostes, R C; Carvalho, M H; Fortes, Z B; Zorn, T M; San Martin, S



Maternal and Newborn Services in Marion County.  

National Technical Information Service (NTIS)

The report describes the status of maternal and newborn services in Marion County, Indiana, and the maternal and newborn health indicators which are measures of maternal and newborn health services: birth projections, incidence of prenatal care, number of...

R. Brand



Society for Maternal-Fetal Medicine  


... the un-routine The Society for Maternal-Fetal Medicine We partner with referring providers, medical societies, payers ... moms and babies. View Find a Maternal-Fetal Medicine Specialist More than 2,000 Maternal-Fetal Medicine ...


Dietary protein restriction and excess of pregnant German Landrace sows induce changes in hepatic gene expression and promoter methylation of key metabolic genes in the offspring.  


Maternal nutrition during gestation has important effects on offspring gene expression mediated by DNA methylation. In order to evaluate the effect of restricted and excess protein intake during gestation, hepatic gene expression and DNA methylation of key metabolic genes NR3C1, PPAR?, HMGCR, PGC1?, INSR and CYP2C34 were investigated. Liver samples of German Landrace offspring were collected at Gestational Day 95, at birth, at weaning and from finisher pigs. Gene expression in foetal liver revealed significant differences between the control group (CO) and the low-protein group (LP) in HMGCR (P<.0001), INSR (P=.0003), NR3C1 (P=.020) and PGC1? (P=.003). At birth INSR (P=.032), PPAR? (P=.0006) and CYP2C34 (P<.0001) showed significant differences between LP and CO. CYP2C34 was significantly increased in the high-protein group (HP) compared to CO (P=.001). At weaning, INSR was significantly higher expressed in LP than in CO (P=.018). HMGCR showed a significant decrease of transcript amount in HP compared to CO (P=.0006). Furthermore, we studied the question whether gene expression differences between distinct diet groups are a result of differential DNA methylation status. CpG sites in the 5'-flanking region of CYP2C34 showed a significant positive correlation with transcript amount in LP (nt -137: R=0.67, P<.0001; nt -112: R=0.54, P=.003). In NR3C1 methylation, differences in the CpG island were negatively correlated with gene expression data in LP (R=-0.34, P=.032). The mean of methylation of PPAR? over CpG sites from nt -220 to -11 was significantly increased in the LP group compared with CO (P=.043). These data suggest an influence of DNA methylation in nutrient-dependent transcriptional regulation of NR3C1, PPAR? and CYP2C34. PMID:22749136

Altmann, Simone; Murani, Eduard; Schwerin, Manfred; Metges, Cornelia C; Wimmers, Klaus; Ponsuksili, Siriluck



Commentary on the role of maternal toxicity on developmental toxicity.  


Maternal mammalian toxicity impacts prenatal development, with general systemic maternal toxicity, from reduced weight gain to morbidity, causative for reduced fetal weights/litter and increased fetal variations (especially skeletal)/litter, but not, in the author's opinion, for increased fetal malformations, reduced litter sizes or full litter losses. Increased fetal malformations are likely due to exposure to specific chemicals which alter specific maternal functions at critical point(s) in pregnancy, typically exaggerated effects from higher doses by drugs under development with known, desired pharmacological effects. Malformations can also be from genetic/epigenetic alterations, specific altered proteins, molecular pathways, etc. Full litter losses are triggered by the mother and are rare in rats. Information to inform maternal (and developmental) toxicity includes ovarian corpora lutea counts, uterine implantation profile, degree of litter reduction (if present), timing and extent of maternal toxicity relative to those of adverse embryofetal effects, etc. The view of maternal toxicity as confounding results in in vivo developmental toxicity studies, worldwide concerns about increased research animal usage, increasing time, labor, costs, and new software and hardware sophistication all drive the interest in development, validation, and performance of in vitro/in silico assays. These assays are fast, inexpensive, responsive to animal use concerns and amenable to mechanistic questions. The strength of these in vitro/in silico assays is considered by many to be the absence of the maternal organism/placenta. These assays inform mechanism and hazard, but NOT risk. The Environmental Protection Agency currently estimates that these new assays are approximately 70% accurate versus the whole animal tests. PMID:22706915

Tyl, Rochelle W



Long-Lasting Effect of Perinatal Exposure to L-tryptophan on Circadian Clock of Primary Cell Lines Established from Male Offspring Born from Mothers Fed on Dietary Protein Restriction  

PubMed Central

Background & Aims Maternal undernutrition programs metabolic adaptations which are ultimately detrimental to adult. L-tryptophan supplementation was given to manipulate the long-term sequelae of early-life programming by undernutrition and explore whether cultured cells retain circadian clock dysregulation. Methods Male rat pups from mothers fed on low protein (8%, LP) or control (18%, CP) diet were given, one hour before light off, an oral bolus of L-tryptophan (125 mg/kg) between Day-12 and Day-21 of age. Body weight, food intake, blood glucose along with the capacity of colonization of primary cells from biopsies were measured during the young (45–55 days) and adult (110–130 days) phases. Circadian clock oscillations were re-induced by a serum shock over 30 hours on near-confluent cell monolayers to follow PERIOD1 and CLOCK proteins by Fluorescent Linked ImmunoSorbent Assay (FLISA) and period1 and bmal1 mRNA by RT-PCR. Cell survival in amino acid-free conditions were used to measure circadian expression of MAP-LC3B, MAP-LC3B-FP and Survivin. Results Tryptophan supplementation did not alter body weight gain nor feeding pattern. By three-way ANOVA of blood glucose, sampling time was found significant during all phases. A significant interaction between daily bolus (Tryptophan, saline) and diets (LP, CP) were found during young (p?=?0.0291) and adult (p?=?0.0285) phases. In adult phase, the capacity of colonization at seeding of primary cells was twice lower for LP rats. By three-way ANOVA of PERIOD1 perinuclear/nuclear immunoreactivity during young phase, we found a significant effect of diets (p?=?0.049), daily bolus (p<0.0001) and synchronizer hours (p?=?0.0002). All factors were significantly interacting (p?=?0.0148). MAP-LC3B, MAP-LC3B-FP and Survivin were altered according to diets in young phase. Conclusions Sequelae of early-life undernutrition and the effects of L-tryptophan supplementation can be monitored non-invasively by circadian sampling of blood D-glucose and on the expression of PERIOD1 protein in established primary cell lines.

Nascimento, Elizabeth; Guzman-Quevedo, Omar; Delacourt, Nellie; da Silva Aragao, Raquel; Perez-Garcia, Georgina; de Souza, Sandra Lopes; Manhaes-de-Castro, Raul; Bolanos-Jimenez, Francisco; Kaeffer, Bertrand



Chronic exposure to light reverses the effect of maternal separation on proteins in the prefrontal cortex.  


Animals subjected to maternal separation display behavioural and endocrine disturbances, as well as structural and functional changes in the prefrontal cortex and limbic areas. The aim of the present study was to determine the effect of maternal separation and treatment with either chronic constant light exposure or anti-depressant (escitalopram) on proteins in the prefrontal cortex. Four experimental groups of male Sprague-Dawley rats were subjected to (1) normal rearing, (2) maternal separation (3 h per day from postnatal day 2 (P2) to P14), (3) maternal separation followed by chronic light exposure (P42-P63) or (4) maternal separation followed by treatment with the anti-depressant drug, escitalopram (P68-P100). Groups 1-3 were treated with saline as vehicle control for the escitalopram-treated group. At P101, all rats were decapitated, and the prefrontal cortex was collected and stored at -80 °C. Tissue from three rats per group was pooled and proteins determined by isobaric tagging for relative and absolute quantification using matrix-assisted laser desorption/ionisation tandem mass spectrometry. Maternal separation led to disruptions in the prefrontal cortex that included hypometabolism by decreasing energy-related proteins (creatine kinase B, aconitate hydratase), decreased cell signalling (synapsin I, calmodulin, 14-3-3 protein epsilon) and impaired plasticity (spectrin, microtubule-associated protein). Maternal separation also increased dihydropyrimidinase-related protein/collapsin response mediator protein (CRMP) and myelin proteolipid protein. Exposure of maternally separated animals to constant light during adolescence reversed the hypometabolic state by increasing energy-related proteins in the prefrontal cortex and increasing cell signalling and cytoskeletal proteins and decreasing the expression of CRMP. Escitalopram had similar effects to light by increasing ATP synthase in maternally separated rats and dissimilar effects by increasing 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin proteolipid protein. Constant light exposure during adolescence reversed a range of protein changes in the prefrontal cortex of rats exposed to early maternal separation. The most prominent reversal by light treatment of maternal separation-induced protein increases in the prefrontal cortex was the expression of CRMP which impairs plasticity and neuronal signalling. The effects of light treatment overlapped partially with the effects of escitalopram. PMID:23884545

Dimatelis, J J; Stein, D J; Russell, V A



Maternal health and mongolism.  


Preliminary findings of an analysis of the occurrence of mongolism among 25,000 babies born in Framingham, Massachusetts, in the 12-year period from 1960-1971 are reported. During the 12 years, 31 mongoloid babies were born to residents, and 12 (39%) were born in the 2-year period of 1970 and 1971, with the rate of mongolism approaching 5/1000 births in 1971 despite an overall decline in the birth rate. Maternal health factors and clinical tests of the offspring (karyotyping, x-ray, and photography) provided the data to make the following conclusions. First, that although the well-known tendency of older women to give birth to mongoloid children was confirmed, it was found that no age groups were exempt. Overall, the largest number of mongoloid infants in 1971 came from mothers whose families were apparently completed, and who had been using an unreliable (e.g., calendar rhythm method) contraceptive measure; most of the women reported these pregnancies as unexpected, unplanned, and unwanted. In all 15 of the 31 mongoloid babies born since January 1, 1960, were born to women over 35 years old, whereas 7 mothers with mongoloid offspring were under 25 years of age, 1 of whom was a translocation carrier. In addition to genetic alterations such as trisomies, monosomies, and aneuploidies which may be of natural causes in humans, other suspected causes of mongolism in humans are significant delays in fertilization of oocyte because of maternal age, chance postponement of critical mating because of ignorance of the endocrine timetable, and crude attempts to use temperature charts for contraception. PMID:4114213

Ingalls, T H



Maternal Worry About Neonatal Hearing Screening  

Microsoft Academic Search

OBJECTIVE: To identify and compare the prevalence and degree of maternal worry about neonatal hearing screening at the time of an initial neonatal hearing screen and rescreen in 1997 and 1999.STUDY DESIGN: We report on a prospective cross-sectional investigation of maternal worry about newborn hearing screening. Demographic data, maternal knowledge of hearing screening, and degree of maternal worry were collected

Betty R Vohr; Kristen S Letourneau; Cheryl McDermott



Maternal diet amplifies the hepatic aging trajectory of Cidea in male mice and leads to the development of fatty liver.  


The importance of the early environment on long-term heath and life span is well documented. However, the molecular mechanisms mediating these effects remain poorly understood. Male offspring from a maternal protein restriction model, in which animals are exposed to a low-protein diet while in utero and then are cross-fostered to normally fed dams, demonstrate low birth weight, catch-up growth, and reduced life span (recuperated offspring). In the current study, we used microarray analysis to identify hepatic genes that changed with age. Cell death-inducing DNA fragmentation factor, ? subunit-like effector A (Cidea), a transcriptional coactivator that has been implicated in lipid accumulation demonstrated one of the largest age-associated increases in expression (200-fold, P<0.001). This increase was exaggerated ?3-fold in recuperated offspring. These demonstrated increased hepatic lipid accumulation, higher levels of transcription factors important in lipid regulation, and greater oxidative stress. In vitro analysis revealed that Cidea expression was regulated by oxidative stress and DNA methylation. These findings suggest that maternal diet modulates the age-associated changes in Cidea expression through several mechanisms. This expression affects hepatic lipid metabolism in these animals and thus provides a mechanism by which maternal diet can contribute to the metabolic health and ultimately the life span of the offspring. PMID:24481968

Carr, Sarah K; Chen, Jian-Hua; Cooper, Wendy N; Constância, Miguel; Yeo, Giles S H; Ozanne, Susan E



Low-protein diet in adult male rats has long-term effects on metabolism.  


Nutritional insults during developmental plasticity have been linked with metabolic diseases such as diabetes in adulthood. We aimed to investigate whether a low-protein (LP) diet at the beginning of adulthood is able to program metabolic disruptions in rats. While control rats ate a normal-protein (23%; NP group) diet, treated rats were fed a LP (4%; LP group) diet from 60 to 90 days of age, after which an NP diet was supplied until they were 150 days old. Plasma levels of glucose and insulin, autonomous nervous system (ANS), and pancreatic islet function were then evaluated. Compared with the NP group, LP rats exhibited unchanged body weight and reduced food intake throughout the period of protein restriction; however, after the switch to the NP diet, hyperphagia of 10% (P<0.05), and catch-up growth of 113% (P<0.0001) were found. The LP rats showed hyperglycemia, insulin resistance, and higher fat accretion than the NP rats. While the sympathetic tonus from LP rats reduced by 28%, the vagus tonus increased by 21% (P<0.05). Compared with the islets from NP rats, the glucose insulinotropic effect as well as cholinergic and adrenergic actions was unaltered in the islets from LP rats. Protein restriction at the beginning of adulthood induced unbalanced ANS activity and fat tissue accretion later in life, even without functional disturbances in the pancreatic islets. PMID:24599936

Malta, Ananda; de Oliveira, Júlio Cezar; Ribeiro, Tatiane Aparecida da Silva; Tófolo, Laize Peron; Barella, Luiz Felipe; Prates, Kelly Valério; Miranda, Rosiane Aparecida; Elmhiri, Ghada; Franco, Claudinéia Conationi da Silva; Agostinho, Aryane Rodrigues; Trombini, Amanda Bianchi; Pavanello, Audrei; Gravena, Clarice; Abdennebi-Najar, Latifa; Mathias, Paulo Cezar de Freitas



Fetal-maternal erythrocyte distribution  


The fetal-maternal erythrocyte distribution test is used to measure the number of the unborn baby's red blood cells ... that has been exchanged between the mother and fetus. All Rh- pregnant women should get this test ...


Interactive Fly: Maternally transcribed genes  

NSDL National Science Digital Library

The maternally transcribed genes section of the award-winning and comprehensive site: Interactive fly. It thoroughly discusses genes, tissues, biochemical paths, and developmental processes in the fruit fly, Drosophila.

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)



Partnership Transitions and Maternal Parenting  

PubMed Central

We use data from the Fragile Families and Child Wellbeing Study (N = 1,975) to examine the association between mothers’ partnership changes and parenting behavior during the first five years of their children’s lives. We compare coresidential with dating transitions, and recent with more distal transitions. We also examine interactions between transitions and race/ethnicity, maternal education and family structure at birth. Findings indicate that both coresidential and dating transitions were associated with higher levels of maternal stress and harsh parenting; recent transitions had stronger associations than distal transitions. Maternal education significantly moderates these associations, with less educated mothers responding more negatively to instability in terms of maternal stress, and more educated mothers responding more negatively in terms of literacy activities.

Beck, Audrey N.; Cooper, Carey E.; McLanahan, Sara; Brooks-Gunn, Jeanne



Maternal and Child Health Bureau  


... Maternal, Infant and Early Childhood Home Visiting Formula Grant Program Limited Competition Apply at by ... by June 02 HRSA-14-030 State Implementation Grants for Enhancing the System of Services for Children ...


Maternal behavior and developmental psychopathology.  


This paper reviews recent developments in the phenomenology, neurobiology, and genetics of maternal behavior in animal model systems from an evolutionary perspective on psychopathology. Following a review of the phenomenology and neurobiology of maternal behavior, recent studies addressing the role of genetic factors in the maternal behavior of rodents were identified in a search of literature in peer-reviewed journals. Gene knockout studies were evaluated with regard to mouse strain background, method of behavioral phenotyping, and quantification of the behavioral deficits. Gene knockout data were then analyzed using a cluster analysis technique. At least nine genes have been identified that are necessary for the expression of one or more aspects of maternal behavior. These genes encode for three transcription factors: three enzymes, including dopamine beta hydroxylase and neuronal nitric oxide synthase; two receptors, including the prolactin and the estrogen alpha receptor; and one neuropeptide, oxytocin. Cluster analysis suggested possible relationships between specific genes. Gene knockout technology has provided new insights into the molecular basis of maternal behavior that are congruent with the existing neurobiological literature. Future studies of genetic and environmental influences on maternal behavior have the potential to inform models of disease pathogenesis. PMID:11801229

Leckman, James F; Herman, Amy E



Maternal-perinatal calcium relationships.  


Serum concentrations of total and ionic calcium, magnesium, phosphorus, and albumin were measureed in maternal and cord blood of 115 near-term deliveries. The same measurements (except for ionic calcium) were made in blood obtained from corresponding newborns at 24 hours of age. Cord levels of all components exceeded maternal values, and maternal and cord levels correlated significantly with each other. In the case of calcium, the cord-maternal difference involved both ionic and protein-bound forms. Significant umbilical arterio-venous differences were found only in the case of total calcium, and this difference reflected variation in the protein-bound form only. During the first 24 hours postpartum, total calcium concentration fell (by an average of 0.75 mEq/liter), phosphorus levels rose (by an average of 0.63 mg/dl), and magnesium and albumin did not change significantly. Cord levels of all agents correlated significantly with corresponding neonatal values. In view of the significant positive relationships demonstrated between maternal and cord levels and between cord and neonatal levels, these results substantiate the importance of the maternal serum ionic calcium concentration in normal perinatal calcium homeostasis. PMID:760023

Schauberger, C W; Pitkin, R M



Maternal and child health. Maternal mortality in the Americas.  


Maternal health in Latin America and the Caribbean continues to be an important issue, which is significantly affected by access to appropriate health technology and quality care, which in turn may be dependent upon economic conditions. Although contraceptive knowledge was high, only 53% of couples used some method of contraception. About 32% and 37% of maternal mortality in Mexico and Colombia could have been averted if contraception had been used. One study of 240 maternal deaths in Mexico indicated that 85% were potentially preventable, and 70% could have been potentially avoided with better medical and institutional care. The table gave the number and rate of maternal mortality and risk by country. In 23 countries, maternal mortality was one of the ten leading causes of death among women. The five prominent causes tended to be abortion, hemorrhage, toxemia, complications of the puerperium, and indirect causes among women aged 15-49 years. Countries can be grouped by level of maternal mortality: 227/100,000 live births, 133/100,000, and 50/100,000. About 280,000 to 420,000 episodes of severe intercurrent obstetric problems potentially occurred annually among the 12 million women of reproductive age in the region. In the United States about 1 out of every 5 pregnancies involved pregnancy related hospitalization in 1987. In Mexico in 1989, of the 740,000 obstetric related discharges for obstetric reasons, 80.5% were related to delivery and 19.5%, to morbidity during pregnancy. During the prenatal period, the five leading causes of morbidity have been identified as premature rupture of membranes, urinary tract infection, potential premature delivery, pre-eclampsia, and pregnancy induced hypertension. Latin American is also a region with increasing numbers of cesarean section deliveries. Maternal deaths in Latin America and the Caribbean would be reduced 47 times and 85% of deaths could be avoided if the health systems paralleled those in Canada. PMID:8240944



Maternity Leave in Taiwan  

PubMed Central

Using the first nationally representative birth cohort study in Taiwan, this paper examines the role that maternity leave policy in Taiwan plays in the timing of mothers returning to work after giving birth, as well as the extent to which this timing is linked to the amount of time mothers spend with their children and their use of breast milk versus formula. We found that the time when mothers returned to work coincided with the duration of guaranteed leave. In particular, mothers with a labor pension plan resumed work significantly earlier than mothers with no pension plan, and mothers with no pension plan returned to work significantly later than those with pension plans. The short leave of absence guaranteed under existing policies translated into mothers spending less time with their children and being more likely to exclusively use formula by 6 months after birth. In contrast, mothers who resumed work later than 6 months after birth were more likely to have not worked before birth or to have quit their jobs during pregnancy. Implications and recommendations for parental leave policy in Taiwan are discussed.

Feng, Joyce Yen; Han, Wen-Jui



Maternal programming of defensive responses through sustained effects on gene expression  

PubMed Central

There are profound maternal effects on individual differences in defensive responses in species ranging from plants to insects to birds. In this paper, we review data from the rat that suggest comparable forms of maternal effects on defensive responses to stress, which are mediated by the effects of variations in maternal behaviour on gene expression. Under conditions of environmental adversity, maternal effects enhance the capacity for defensive responses in the offspring. These effects appear to “program” emotional, cognitive and endocrine systems toward increased sensitivity to adversity. In environments with an increased level of adversity, such effects can be considered adaptive, enhancing the capacity for responses that have immediate adaptive value; the cost is an increased risk for multiple forms of pathology in later life.

Diorio, Josie; Meaney, Michael J.



Maternal toxicity in humans and animals: effects on fetal development and criteria for detection.  


Evaluation of published human and animal teratology data revealed associations between maternal toxicity and congenital malformations and embryofetal death. This has been reported elsewhere in detail and is herein summarized. Regarding human data, intrauterine deaths were observed to occur in association with 1) maternal homeostatic changes due to phenylketonuria and diabetes and 2) maternal toxicity resulting from alcohol abuse, use of aminopterin, and, possibly, trimethadione. A pattern of malformations that was similar and thus suggestive of a common cause was noticed among malformations attributed to phenylketonuria, diabetes mellitus, aminopterin, alcohol, warfarin, phenytoin, phenobarbital, trimethadione, and valproic acid. On reviewing 234 studies of agents tested in hamsters, mice, rats and rabbits, a fairly strong association between maternal toxicity and embryo-fetal mortality was observed. Further, a consistent pattern of fetal malformations associated with maternotoxic effects was discovered in a survey of 476 studies of agents tested in these four species. In th