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1

Modest maternal protein restriction fails to program adult hypertension in female rats.  

PubMed

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50-65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 +/- 3 mmHg vs. NP: 121 +/- 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 +/- 2,071 vs. NP: 26,248 +/- 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 +/- 0.11 10(6) microm(3), LP vs. NP: 1.07 +/- 0.11 10(6) microm(3)); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender. PMID:15961538

Woods, Lori L; Ingelfinger, Julie R; Rasch, Ruth

2005-10-01

2

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins  

Microsoft Academic Search

BACKGROUND: Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma

Ruth Cornock; Simon C Langley-Evans; Ali Mobasheri; Sarah McMullen

2010-01-01

3

Intergenerational programming of impaired nephrogenesis and hypertension in rats following maternal protein restriction during pregnancy.  

PubMed

Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (CON; n 10) or MLP (n 10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F1 generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure produced an F3 generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F1 generation MLP-exposed offspring exhibited raised (P < 0.001) systolic blood pressure (male 143 (sem 4) mmHg; female 141 (sem 4) mmHg) compared with CON animals (male 132 (sem 3) mmHg; female 134 (sem 4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F2 generation (P < 0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (MLP x CON, CON x MLP and MLP x MLP) were hypertensive (132 (sem 3) mmHg) compared with CON animals (CON x CON; 123 (sem 2) mmHg). No effect was noted in the F3 generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation. PMID:18778527

Harrison, Matthew; Langley-Evans, Simon C

2009-04-01

4

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

PubMed

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

2014-08-01

5

Maternal protein restriction reduces expression of angiotensin I-converting enzyme 2 in rat placental labyrinth zone in late pregnancy.  

PubMed

Both the systemic and the uteroplacental renin-angiotensin system (RAS) display dramatic changes during pregnancy. However, whether gestational protein insufficiency affects the expressions of RAS in the placenta remains unknown. In this study, we hypothesized that the expression of Ace2 in the placental labyrinth was reduced by maternal protein restriction. Pregnant Sprague-Dawley rats were fed a normal diet or a low-protein diet (LP) from Day 1 of pregnancy until they were killed at Day 14 or Day 18. The labyrinth zone (LZ) of the placenta was then dissected and snap frozen for expression analysis by quantitative real-time PCR of Ace, Ace2, Agtr1a, Agtr1b, and Agtr2. Formalin-fixed placentas were used for immunohistochemical analysis on ACE and ACE2 proteins. The findings include 1) the expression of Ace2 in rat LZ was reduced by maternal protein restriction in late pregnancy; 2) ACE protein was mainly present in syncytiotrophoblasts, whereas ACE2 protein was found predominantly in fetal mesenchymal tissue and fetal capillaries; 3) Agtr1a was predominant in the rat LZ, and its mRNA levels, but not protein levels, were reduced by LP; 4) expressions of Ace, Ace2, and Agtr1a in the rat LZ and their response to LP occurred in a gender-dependent manner. These results may indicate that a reduced expression of Ace2 and perhaps an associated reduction in angiotensin (1-7) production in the placenta by maternal protein restriction may be responsible for fetal growth restriction and associated programming of adulthood hypertension. PMID:22011389

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2012-02-01

6

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

PubMed Central

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

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

2014-01-01

7

Maternal protein restriction reduces angiotensin II AT(1) and AT(2) receptor expression in the fetal rat kidney.  

PubMed

Maternal dietary protein restriction during pregnancy results in an increase in offspring blood pressure in the rat. The kidneys of the low protein (LP) rat have fewer nephrons, increased hemodynamic sensitivity to angiotensin II and lower glomerular filtration rate, suggesting altered activity of the renin-angiotensin system. Angiotensin II plays a role in nephrogenesis through the AT(1) and AT(2) receptor subtypes. The aim of this study was to determine expression levels of both subtypes during nephrogenesis. Pregnant Wistar rats were fed either a control 18% protein diet or a low 9% protein (LP) diet. A 35% reduction in nephron number (p < 0.05) associated with a 50% reduction in total glomerular volume (p < 0.001) was seen in LP rats. Renal AT(1) (p < 0.0001) and AT(2) (p < 0.0001) receptor protein expression were significantly lower in LP rats from E18 to day 10. AT(1) expression in LP rat kidneys tended to increase over time while AT(2) expression declined until day 10, when it began to increase again. Angiotensin II-regulated cell proliferation may be perturbed in the LP rat kidney during nephrogenesis which could contribute to the reduction in nephron number and the elevation in blood pressure observed in this model of programmed hypertension. PMID:20606474

Alwasel, Saleh H; Kaleem, Irram; Sahajpal, Vandana; Ashton, Nick

2010-01-01

8

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. PMID:25031729

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

2014-01-01

9

Maternal protein restriction regulates IGF2 system in placental labyrinth  

PubMed Central

This study was to test the hypothesis that altered IGF2 system in the placental labyrinth zone (LZ) impairs feto-placental growth in response to maternal protein restriction. Rats were fed a 20% protein diet and an isocaloric 6% protein diet (LP) from day 1 to days 14, 18, or 21 of pregnancy. The effects of diet, gender of placenta and fetus, and day of pregnancy on placental weight, fetal weight, and expression of the IGF2 axis in the placental LZ and amino acids in maternal plasma were analyzed. Growth restriction occurred in both female and male fetuses by LP, coincident with impaired LZ growth and efficiency. The expression of Igf2, Igf2P0, Igf1r, Igf2r, Insr, Igfbp1, and Igfbp2 in placental LZ were affected by diet, gender and/or day of pregnancy. Concentrations of total essential amino acids and total nonessential amino acids were reduced and increased, respectively, in maternal plasma of LP-fed rats. These results indicate that adaptation of the IGF2 system in rat LZ occurs in a sex- and time-dependent manner in response to maternal protein restriction; however, these adaptations cannot prevent the growth restriction of both male and female fetuses during late pregnancy. PMID:22201967

Gao, Haijun; Sathishkumar, Kunju Reddiar; Yallampalli, Uma; Balakrishnan, Meena; Li, Xilong; Wu, Guoyao; Yallampalli, Chandra

2013-01-01

10

Maternal protein restriction in pregnancy and/or lactation affects seminiferous tubule organization in male rat offspring.  

PubMed

Maternal protein restriction (MPR) during pregnancy impaired the reproduction of male offspring. We investigated, during the first wave of spermatogenesis, whether MPR exerts deleterious effects on germ cell proliferation and differentiation, as well as androgen receptor (AR) protein expression, which was used as a marker for Sertoli cell (SC) maturation. At the beginning of pregnancy (day 0), dams were fed a control diet (C: 20% casein) or a restricted isocaloric diet (R: 10% casein). After birth, four groups were established: CC, RR, CR and RC (first letter diet during pregnancy and second during lactation). Male offspring were studied at postnatal days 14, 21 and 36. At birth, pup body weight was unchanged. Body weight and testis weight were reduced in RR and CR groups at all ages evaluated. MPR delayed the germinal epithelium development at all ages evaluated. On performing Western blot and immunohistochemistry, AR expression was found to be lower in the three restricted groups. The results suggest that MPR during pregnancy and/or lactation delays SC maturation and germ cell differentiation, and affects intratubular organization. These changes might be responsible for the lower fertility rate at older ages. PMID:25102260

Rodríguez-González, G L; Vigueras-Villaseñor, R M; Millán, S; Moran, N; Trejo, R; Nathanielsz, P W; Larrea, F; Zambrano, E

2012-10-01

11

The effects of maternal mild protein restriction on stroke incidence and blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP).  

PubMed

The effect of maternal protein restriction during pregnancy on the offspring's blood pressure was assessed in stroke-prone spontaneously hypertensive rats (SHRSP) which are genetically predisposed to hypertension and stroke. After the confirmation of pregnancy, the control group was given a 20% casein diet, and the low-protein group was fed a 9% casein diet. After the confirmation of delivery, commercial feed was given to both of the groups. No differences were seen between the control and low-protein offspring in regard to body weight, blood pressure elevation, or life span. One percent saline solution was put in the control and low-protein groups after the age of 11 weeks. Blood pressure increased markedly in the low-protein group, on the blood pressure level in the low-protein group on week 2 after salt loading (242+/-6 mmHg) was significantly higher than that in the control group (223+/-9 mmHg; p<0.05). The survival duration was significantly shorter in the low-protein group (113+/-4 days) than in the control group (135+/-22 days; p<0.05). These results suggest that maternal protein malnutrition in SHRSP exerted a high salt sensitivity and a malignant influence on stroke incidence on offspring. PMID:15056877

Otani, Lila; Shirasaka, Norifumi; Yoshizumi, Hajime; Murakami, Tetsuo

2004-03-01

12

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

Microsoft Academic Search

Maternal protein deficiencies can developmentally program offspring to lifelong dysfunction of many physiological systems. We hypothesized that maternal isocaloric low protein diet during fetal and early postnatal development would negatively affect female offspring anxiety, exploration, associative learning and motivation as measured by the elevated plus maze (EPM), open field test (OFT), operant conditioning and the progressive ratio task, respectively. Control

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

13

Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats.  

PubMed

There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a low-protein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed > or =1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity. PMID:15562247

Guan, Haiyan; Arany, Edith; van Beek, Jonathan P; Chamson-Reig, Astrid; Thyssen, Sandra; Hill, David J; Yang, Kaiping

2005-04-01

14

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

PubMed Central

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

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

2014-01-01

15

Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring.  

PubMed

Human adult diseases such as cardiovascular disease, hypertension, and type 2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low-protein (LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin-signaling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine whether female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet, respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 mo of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the two groups; however, LP fasting insulin was approximately twofold that of controls (P < 0.02). Glucose tolerance during IVGTT was comparable between the two groups; however, LP peak plasma insulin at 4 min was approximately threefold higher than in controls (P < 0.001). LP plasma insulin area under the curve was 1.9-fold higher than controls (P < 0.02). In Western blots, both muscle protein kinase C-zeta expression and p110beta-associated p85alpha in abdominal fat were reduced (P < 0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin-signaling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and, hence, an increased risk of type 2 diabetes. PMID:15514105

Fernandez-Twinn, D S; Wayman, A; Ekizoglou, S; Martin, M S; Hales, C N; Ozanne, S E

2005-02-01

16

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

2003-01-01

17

Maternal protein restriction induce skeletal muscle changes without altering the MRFs MyoD and myogenin expression in offspring.  

PubMed

Stimuli during pregnancy, such as protein restriction, can affect morphophysiological parameters in the offspring with consequences in adulthood. The phenomenon known as fetal programming can cause short- and long-term changes in the skeletal muscle phenotype. We investigated the morphology and the myogenic regulatory factors (MRFs) MyoD and myogenin expression in soleus, SOL; oxidative and slow twitching and in extensor digitorum longus, EDL; glycolytic and fast twitching muscles in the offspring of dams subjected to protein restriction during pregnancy. Four groups of male Wistar offspring rats were studied. Offspring from dams fed a low-protein diet (6 % protein, LP) and normal protein diet (17 % protein, NP) were euthanized at 30 and 112 days old, and their muscles were removed and kept at -80 °C. Muscles histological sections (8 ?m) were submitted to a myofibrillar adenosine triphosphatase histochemistry reaction for morphometric analysis. Gene and protein expression levels of MyoD and myogenin were determined by RT-qPCR and western blotting. The major findings observed were distinct patterns of morphological changes in SOL and EDL muscles in LP offspring at 30 and 112 days old without changes in MRFs MyoD and myogenin expression. Our results indicate that maternal protein restriction followed by normal diet after birth induced morphological changes in muscles with distinct morphofunctional characteristics over the long term, but did not alter the MRFs MyoD and myogenin expression. Further studies are necessary to better understand the mechanisms underlying the maternal protein restriction response on skeletal muscle. PMID:22538480

Cabeço, Ludimila Canuto; Budri, Paulo Eduardo; Baroni, Mirella; Castan, Eduardo Paulino; Carani, Fernanda Regina; de Souza, Paula Aiello Tomé; Boer, Patrícia Aline; Matheus, Selma Maria Michelin; Dal-Pai-Silva, Maeli

2012-10-01

18

Maternal protein restriction leads to pancreatic failure in offspring: role of misexpressed microRNA-375.  

PubMed

The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined. In rats, restriction of protein during gestation alters the development of the endocrine pancreas and favors the occurrence of T2D later in life. Here we evaluate the potential role of perturbed microRNA (miRNA) expression in the decreased ?-cell mass and insulin secretion characterizing progeny of pregnant dams fed a low-protein (LP) diet. miRNA profiling shows increased expression of several miRNAs, including miR-375, in the pancreas of fetuses of mothers fed an LP diet. The expression of miR-375 remains augmented in neoformed islets derived from fetuses and in islets from adult (3-month-old) progeny of mothers fed an LP diet. miR-375 regulates the proliferation and insulin secretion of dissociated islet cells, contributing to the reduced ?-cell mass and function of progeny of mothers fed an LP diet. Remarkably, miR-375 normalization in LP-derived islet cells restores ?-cell proliferation and insulin secretion. Our findings suggest the existence of a developmental memory in islets that registers intrauterine protein restriction. Hence, pancreatic failure after in utero malnutrition could result from transgenerational transmission of miRNA misexpression in ?-cells. PMID:24834976

Dumortier, Olivier; Hinault, Charlotte; Gautier, Nadine; Patouraux, Stéphanie; Casamento, Virginie; Van Obberghen, Emmanuel

2014-10-01

19

Effect of postnatal high-protein diet on kidney function of rats exposed to intrauterine protein restriction.  

PubMed

Poor fetal growth is linked with long-term detrimental effects on health in late life. We have previously shown that maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult offspring. The aim of this study was to investigate the influence of a postnatal high-protein (HP) diet on renal development and renal function in rats subjected to a low-protein (LP) diet in fetal life. Sprague-Dawley rats were fed an LP diet throughout pregnancy. Male pups were given either a normal-protein (NP) diet (LP/NP) or HP diet (LP/HP), and normal male pups as control (NP/NP). At 12 wk, LP/HP offspring displayed no increase in glomerular number but showed elevated blood pressure and proteinuria compared with the LP/NP group. There was minimal fusion of foot processes in LP/NP rats compared with a moderate fusion of foot processes and hyperplasia of mesangial cells in LP/HP rats. Renal desmin mRNA levels were elevated in both LP/NP and LP/HP groups but more significantly in the LP/HP group. This study suggests that postnatal HP diet amplifies the renal damage induced by fetal under-nutrition. Podocyte injury may be one of the mechanisms by which fetal protein restriction leads to proteinuria. PMID:20453715

Chen, Jing; Xu, Hong; Shen, Qian; Guo, Wei; Sun, Li

2010-08-01

20

Dietary protein restriction induces steatohepatitis and alters leptin\\/signal transducers and activators of transcription 3 signaling in lactating rats  

Microsoft Academic Search

Dietary protein restriction during lactation affects lipid metabolism and food intake in rats. The goals of this study were to determine the effect of a low-protein diet on a liver damage in lactating rats, to determine whether dietary protein restriction of lactating dams affects the liver health of their offspring and to elucidate the molecular mechanisms underlying the development of

Duk-Hwa Kwon; Wanseok Kang; Yoon Seok Nam; Mi Sun Lee; In Young Lee; Hye Joung Kim; Panchamoorthy Rajasekar; Jae-Hyuk Lee; Myunggi Baik

21

Prenatal dietary docosahexaenoic acid supplementation in combination with protein restriction does not affect blood pressure in adult Wistar rats.  

PubMed

Recent findings indicate that prenatal protein restriction, which leads to elevated blood pressure in adult rats, results in decreased levels of docosahexaenoic acid (DHA) in neonatal rat brain. In light of the evidence of a relationship between dietary DHA and adult blood pressure, the purpose of this study was to ascertain whether prenatal dietary supplementation with DHA would prevent the development of hypertension associated with maternal protein restriction. Throughout gestation, female Wistar rats were fed isocaloric diets containing either 18% casein + 10% corn oil (CON; control), 9% casein + 10% corn oil (LP; low-protein) or 9% casein + 8.5% corn oil + 1.5% DHASCO (LP + 0.6% DHA). DHA increased levels of DHA in neonatal forebrain but there were no effects of LP. At 10 weeks there were no dietary effects on blood pressure measured on four consecutive days using tail-cuff plethysmography. There were also no significant effects measured at 30 weeks, using femoral artery catheterisation, despite adequate power to detect a 10 mm Hg difference. Trends in corticosterone measurements suggested higher stress reactivity in the LP group. These results do not provide strong support for the prenatal low protein model of hypertension and a relation with dietary DHA. PMID:15526988

Martin, D A; McCutcheon, D; Wainwright, P E

2004-06-01

22

Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring.  

PubMed

Low birth weight humans often exhibit hypertension during adulthood. Studying the offspring of rat dams fed a maternal low-protein diet is one model frequently used to study the mechanisms of low birth weight-related hypertension. It remains unclear whether this model replicates key clinical findings of hypertension and increased blood pressure responsiveness to stress or high-salt diet. We measured blood pressure via radiotelemetry in 13-wk-old male offspring of maternal normal- and low-protein dams. Neither group exhibited hypertension at baseline; however, 1 h of restraint was accompanied by a significantly greater blood pressure response in low-protein compared with normal-protein offspring. To enhance the effect of a high-salt diet on blood pressure, normal- and low-protein offspring underwent right uninephrectomy, while controls underwent sham surgery. After 5 weeks on a high-salt diet (4% NaCl), mean arterial pressure in the Low-Protein+Sham offspring was elevated by 6 +/- 2 mmHg (P < 0.05 vs. baseline), while it remained unchanged in the normal-protein offspring. In the two uninephrectomized groups, blood pressure increased further, but was of similar magnitude. Glomerular filtration rate in the low-protein uninephrectomized offspring was 50% less than that in normal-protein offspring with intact kidneys. These data indicate that, while male low-protein offspring are not hypertensive during young adulthood, their blood pressure is hyperresponsive to restraint stress and is salt sensitive, and their glomerular filtration rate is more sensitive to hypertension-causing insults. Collectively, these may predispose for the development of hypertension later in life. PMID:20200128

Augustyniak, Robert A; Singh, Karan; Zeldes, Daniel; Singh, Melissa; Rossi, Noreen F

2010-05-01

23

Sex differences in sensitivity to beta-adrenergic agonist isoproterenol in the isolated adult rat heart following prenatal protein restriction.  

PubMed

Hypertension is a major risk factor for the development of CVD. Epidemiological studies have shown that low birth weight increases the risk of developing hypertension in adulthood. Hypertension increases the risk of suffering IHD and early findings provide evidence that hearts from prenatally protein-restricted, hypertensive, male offspring are more susceptible to cardiac dysfunction following ischaemic events. Hypertension and abnormalities in cardiac function following ischaemia-reperfusion in the human population are treated therapeutically with beta-adrenergic antagonists. We hypothesised that increased susceptibility to myocardial ischaemia-reperfusion injury in prenatally programmed offspring may be due to sympathetic hyperactivity. Pregnant Wistar rats were fed control or low-protein (maternal low protein; MLP) diets throughout gestation. At age 6 months, hearts were rapidly excised and retro-perfused using the Langendorff apparatus, to assess isolated cardiac function following stimulation with increasing doses of the non-specific beta-agonist isoproterenol. Baseline heart rates were similar in control and MLP-fed offspring. With significant diet x sex interactions (P < 0.01) maximum heart rate response following isoproterenol infusion was significantly longer in MLP than control. Prenatal diet had no effect on maximal left ventricular developed pressure (LVDP) response, but the LVDP isoproterenol response was significantly longer in duration in MLP-exposed male offspring (diet x sex P < 0.001). Myocardial mRNA expression of beta2-adrenergic receptors was increased in 2-week-old female MLP offspring only (P < 0.049). In conclusion, maternal protein restriction programmes cardiac sympathetic activity in a sex-specific manner, and may explain increased susceptibility to ischaemia-reperfusion injury in males subject to fetal undernutrition. PMID:18590591

Elmes, Matthew J; Haase, Andrea; Gardner, David S; Langley-Evans, Simon C

2009-03-01

24

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

PubMed

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

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

2014-07-15

25

Gestational protein restriction reduces expression of Hsd17b2 in rat placental labyrinth.  

PubMed

Accumulating evidence strongly supports the premise that testosterone may be a key player in fetal programming on hypertension. Studies have shown that gestational protein restriction doubles the plasma testosterone levels in pregnant rats. In this study, we hypothesized that elevated testosterone levels in response to gestational protein restriction were caused by enhanced expression of steroidogenic enzymes or impaired expression of Hsd17b2, a known testosterone inactivator that converts testosterone to androstenedione in placenta. Pregnant Sprague-Dawley rats were fed normal (20% protein, control; n = 10) or a low-protein diet (6% protein, PR; n = 10) from Day 1 of pregnancy until killed at Days 14, 18, or 21. Junctional (JZ) and labyrinth (LZ) zones of placenta were collected for expression assay on steroidogenic genes (Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b2, and Srd5a1) by real-time PCR. The main findings include the following: 1) expressions of Cyp11a1, Hsd3b1, and Cyp17a1 in JZ were not affected by diet but were affected by day of pregnancy; 2) expression of Hsd17b2 in both female and male JZs was remarkably increased by PR at Days 18 and 21 of pregnancy; 3) expressions of Hsd17b2 were reduced by PR in both female and male LZ at Day 18 of pregnancy and in female LZ at Day 21 of pregnancy; and 4) expression of Srd5a1in LZ was not affected by day of pregnancy, gender, or diet. These results indicate that in response to gestational protein restriction, Hsd17b2 may be a key regulator of testosterone levels and associated activities in placental zones, apparently in a paradoxical manner. PMID:22837477

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2012-09-01

26

Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction.  

PubMed

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-? and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life. PMID:21655297

Menendez-Castro, Carlos; Fahlbusch, Fabian; Cordasic, Nada; Amann, Kerstin; Münzel, Kathrin; Plank, Christian; Wachtveitl, Rainer; Rascher, Wolfgang; Hilgers, Karl F; Hartner, Andrea

2011-01-01

27

Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis  

Microsoft Academic Search

Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis.BackgroundIn rats, offspring born to mothers supplied low protein diets during pregnancy have fewer glomeruli than normal. We hypothesized that such nephron deficits are associated with altered cell turnover in the metanephros, the embryonic precursor of the adult kidney.MethodsWistar rats were supplied with

Simon J. M. Welham; Angela Wade; Adrian S. Woolf

2002-01-01

28

Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress.  

PubMed

Maternal protein restriction (MPR) in pregnancy causes life course organ dysfunction, but few studies link the developmental origins of disease hypothesis to early aging. Suboptimal developmental nutrition increases oxidative stress (OS) and male infertility, damaging sperm function. We hypothesized that MPR in pregnancy accelerates age-related changes in testicular and sperm function related to both maternal diet and increased testicular OS in rat offspring. We studied male rats whose pregnant mothers ate either control (C, 20 % casein) or restricted (R, 10 % casein) isocaloric diet. After birth, mothers and offspring ate C diet. Testes were retrieved at 19 days gestation and across the life course (postnatal day (PND) 21, 36, 110, and 850) to measure OS markers, antioxidant enzymes, serum FSH, LH, and testosterone, and PND 110 sperm OS and quality. Fertility rate was evaluated at PND 110, 450, and 850. Offspring showed age- and MPR-related changes in testosterone, testicular OS markers and antioxidant enzymes and fertility, and maternal diet-related OS and sperm antioxidant enzyme changes. Developmental programming is considered a key factor in predisposing to chronic disease. Our data show that programming also plays an important role in aging trajectory. This interaction is a little studied area in aging biology that merits more investigation. PMID:25354645

Rodríguez-González, Guadalupe L; Reyes-Castro, Luis A; Vega, Claudia C; Boeck, Lourdes; Ibáñez, Carlos; Nathanielsz, Peter W; Larrea, Fernando; Zambrano, Elena

2014-12-01

29

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

PubMed

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

2012-08-01

30

Intrauterine Exposure to a Maternal Low Protein Diet Reduces Adult Bone Mass and Alters Growth Plate Morphology in Rats  

Microsoft Academic Search

Epidemiological studies suggest that poor growth during fetal life and infancy is associated with decreased bone mass in adulthood. However, theses observations have not, to date, been corroborated in animal models. To address this issue we evaluated the influence of maternal protein restriction on bone mass and growth plate morphology among the adult offspring, using a rat model. Maternal protein

G. Mehta; H. I. Roach; S. Langley-Evans; P. Taylor; I. Reading; R. O. C. Oreffo; A. Aihie-Sayer; N. M. P. Clarke; C. Cooper

2002-01-01

31

Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver.  

PubMed

Caloric restriction (CR) decreases oxidative damage, which contributes to the slowing of aging rate. It is not known if such decreases are due to calories themselves or specific dietary components. In this work, the ingestion of proteins of Wistar rats was decreased by 40% below that of controls. After 7 weeks, the liver of the protein-restricted (PR) animals showed decreases in oxidative protein damage, degree of membrane unsaturation, and mitochondrial complex I content. The results and previous information suggest that the decrease in the rate of aging induced by PR can be due in part to decreases in mitochondrial reactive oxygen species production and DNA and protein oxidative modification, increases in fatty acid components more resistant to oxidative damage, and decreased expression of complex I, analogously to what occurs during CR. Recent studies suggest that those benefits of PR could be caused, in turn, by the lowered methionine intake of that dietary manipulation. PMID:17452727

Ayala, Victoria; Naudí, Alba; Sanz, Alberto; Caro, Pilar; Portero-Otin, Manuel; Barja, Gustavo; Pamplona, Reinald

2007-04-01

32

Hepatic structural alteration in adult programmed offspring (severe maternal protein restriction) is aggravated by post-weaning high-fat diet.  

PubMed

The present study aimed to evaluate the effects of a post-weaning high-fat (HF) diet upon hepatic morphology in rats subjected to perinatal protein restriction. Pregnant Wistar rats were assigned to a normal-protein diet (NP; with 19 % of protein) or a low-protein (LP) diet (with 5 % of protein). At weaning, the following groups were formed: NP and NP-HF, males and females, which were fed standard chow and an HF diet, respectively. Likewise, LP rat dams originated LP and LP-HF offspring, both sexes. Euthanasia was performed at 6 months of age. Three-way ANOVA disclosed a three-factor interaction among sex, perinatal diet and HF diet in relation to body mass, retroperitoneal fat pad, liver mass:tibia length ratio, binucleation rate and hepatocyte area at 6 months old (P < 0.05). The high-fat diet intensified the effects of perinatal protein restriction concerning systolic blood pressure, genital fat pad and hepatocyte number (P < 0.05; two-way ANOVA). Furthermore, higher steatosis rates and insulin and leptin concentrations were found in males fed on the HF diet, indicating a sex-post-weaning diet interaction (P < 0.05; two-way ANOVA). Fetal programming and HF diet as a single stimulus caused mild hypertension at 3 months, an important reduction in hepatocyte number as well as stage 1 steatosis at 6 months. However, hypertension and hepatocyte number deficit were worsened and grade 2 steatosis occurred after exposure to the HF diet. All of these serve to highlight the paramount importance of intra-uterine conditions and postnatal diet quality when it comes to the pathogenesis of chronic diseases. PMID:17559700

Souza-Mello, Vanessa; Mandarim-de-Lacerda, Carlos A; Aguila, Márcia B

2007-12-01

33

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

PubMed

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

Hallam, Megan C; Reimer, Raylene A

2014-10-01

34

Long-Term Modification of the Excretion of Prostaglandin E2 by Fetal Exposure to a Maternal Low Protein Diet in the Rat  

Microsoft Academic Search

Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal

Rachel C. Sherman; Alan A. Jackson; Simon C. Langley-Evans

1999-01-01

35

Laboratory Investigations Intrauterine Exposure to a Maternal Low Protein Diet Reduces Adult Bone Mass and Alters Growth Plate Morphology in Rats  

Microsoft Academic Search

Epidemiological studies suggest that poor growth during fetal life and infancy is associated with decreased bone mass in adulthood. However, these observations have not, to date, been corroborated in animal models. To address this issue we evaluated the influence of maternal protein restriction on bone mass and growth plate morphology among the adult offspring, using a rat model. Maternal protein

G. Mehta; H. I. Roach; S. Langley-Evans; P. Taylor; R. O. C. Oreffo; A. Aihie-Sayer

36

Effects of dietary protein restriction on nephron number in the mouse.  

PubMed

In rats, maternal protein restriction reduces nephron endowment and often leads to adult hypertension. Sex differences in these responses have been identified. The molecular and genetic bases of these phenomena can best be identified in a mouse model, but effects of maternal protein restriction on kidney development have not been examined in mice. Therefore, we determined how combined prenatal and postnatal protein restriction in mice affects organ weight, glomerular number and dimensions, and renal expression of angiotensin receptor mRNA, in both male and female offspring. C57/BL6/129sv mice received either a normal (20% wt/wt; NP) or low (9% wt/wt; LP) protein diet during gestation and postnatal life. Offspring were examined at postnatal day 30. Protein restriction retarded growth of the kidney, liver, spleen, heart, and brain. All organs except the brain weighed less in female than male offspring. Protein restriction increased normalized (to body weight) brain weight, with females having relatively heavier brains than males. The effects of protein restriction were not sex dependent, except that normalized liver weight was reduced in males but increased in females. Glomerular volume, but not number, was greater in female than in male mice. Maternal protein restriction reduced nephron endowment similarly in male and female mice. Renal expression of AT(1A) receptor mRNA was approximately sixfold greater in female than male NP mice, but similar in male LP and female LP mice. We conclude that maternal protein restriction reduces nephron endowment in mice. This effect provides a basis for future studies of developmental programming in the mouse. PMID:17272668

Hoppe, Chantal C; Evans, Roger G; Bertram, John F; Moritz, Karen M

2007-05-01

37

The Effects of Prenatal Protein Restriction on ?-Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion.  

PubMed

A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR) and related this to cardiac expression of ?-adrenergic receptors (?-AR) and their associated G proteins. Pregnant rats were fed control (CON) or MLP diets (n = 12 each group) throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30?min ischemia and 60?min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP) and dP/dt(max) (P < 0.01) during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of ?(2)-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of ?(2)-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of ?(2)-AR and catecholamine levels were protected from IR injury. PMID:22536490

Ryan, Kevin J P; Elmes, Matthew J; Langley-Evans, Simon C

2012-01-01

38

Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction.  

PubMed

Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet +/-5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function. PMID:16585422

Torrens, Christopher; Brawley, Lee; Anthony, Frederick W; Dance, Caroline S; Dunn, Rebecca; Jackson, Alan A; Poston, Lucilla; Hanson, Mark A

2006-05-01

39

Regulation of postnatal pancreatic Pdx1 and downstream target genes after gestational exposure to protein restriction in rats.  

PubMed

The study carried out in our laboratory demonstrated that protein restriction (low protein, LP) during fetal and neonatal life alters pancreatic development and impairs glucose tolerance later in life. In this study, we examined the role of the transcription factor Pdx1, a master regulator of ?-cell differentiation and function along with its downstream target genes insulin, Glut2 and glucokinase (GK). The role(s) of these genes and protein products on the pancreata of male offspring from mothers exposed to LP diets were assessed during gestation, weaning, and adult life. Pregnant rats were allocated to two dietary treatments: control (C) 20% protein diet or LP, 8% protein diet. At birth, offspring were divided into four groups: C received control diet all life, LP1 received LP diet all life, LP2 changed the LP diet to C at weaning, and LP3 switched to C after being exposed to LP during gestation only. Body weights (bw) were significantly (P<0.001) decreased in all LP groups at birth. At weaning, only the LP3 offspring had their body weight restored to control levels. Pdx1 or any of the Pdx1-target genes were similar in all diets at day 21. However, at d130 Pdx1 mRNA expression and protein abundance were significantly decreased (P<0.05) in all LP groups. In addition, insulin mRNA and protein were decreased in LP1 and LP3 groups compared with C, Glut2 mRNA and GLUT2 protein levels were decreased in LP3 and GK did not change between groups. Intraperitoneal glucose tolerance test revealed impaired glucose tolerance in LP3 males, concomitant with decreased ?-cell mass, islet area, and PDX1 nuclear protein localization. Collectively, this study suggests that restoring proteins in the diet after birth in LP offspring dramatically impairs glucose homeostasis in early adulthood, by altering Pdx1 expression and downstream-target genes increasing the risk to develop type 2 diabetes. PMID:25667428

Abuzgaia, Awatif M; Hardy, Daniel B; Arany, Edith

2015-03-01

40

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.  

PubMed

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

2014-01-28

41

Maternal low-protein diet during lactation programmes body composition and glucose homeostasis in the adult rat offspring.  

PubMed

Previously we have reported that maternal malnutrition during lactation programmes body weight and thyroid function in the adult offspring. In the present study we evaluated the effect of maternal protein restriction during lactation upon body composition and hormones related to glucose homeostasis in adult rats. During lactation, Wistar lactating rats and their pups were divided into two experimental groups: control (fed a normal diet; 23% protein) and protein-restricted (PR; fed a diet containing 8% protein). At weaning, offspring received a normal diet until they were 180 d old. Body weight (BW) and food intake were monitored. Serum, adrenal glands, visceral fat mass (VFM) and carcasses were collected. PR rats showed lower BW (-13%; P < 0.05), VFM (-33%; P < 0.05), total body fat (-33%; P < 0.05), serum glucose (-7%; P < 0.05), serum insulin (-26%, P < 0.05), homeostasis model assessment index (-20%), but higher total adrenal catecholamine content (+90%; P < 0.05) and serum corticosterone concentration (+51%; P < 0.05). No change was observed in food intake, protein mass or total body water. The lower BW of PR rats is due to a reduction of white fat tissue, probably caused by an increase in lipolysis or impairment of lipogenesis; both effects could be related to higher catecholaminergic status, as well as to hypoinsulinaemia. To conclude, changes in key hormones which control intermediary metabolism are programmed by maternal protein restriction during lactation, resulting in BW alterations in adult rats. PMID:17524178

Fagundes, A T S; Moura, E G; Passos, M C F; Oliveira, E; Toste, F P; Bonomo, I T; Trevenzoli, I H; Garcia, R M G; Lisboa, P C

2007-11-01

42

Influence of angiotensin II type 1 receptor-associated protein on prenatal development and adult hypertension after maternal dietary protein restriction during pregnancy.  

PubMed

An adverse relationship between suboptimal fetal environments and the development of adult diseases, such as hypertension, type II diabetes, and cardiovascular disease, has been reported in numerous studies. The purpose of this study was to investigate the strain difference of offspring's response to maternal malnutrition during pregnancy and the involvement of the renin-angiotensin system (RAS) in the development of adult hypertension using C57BL/6J (C57) mice and angiotensin II (Ang II) type 1 receptor-associated protein-transgenic (ATRAP-Tg) mice. Pregnant dams were fed an isocaloric diet containing either 20% (normal protein; NP) or 8% (low protein; LP) protein. Birth weight was significantly reduced in C57-LP offspring, but not in ATRAP-Tg-LP offspring. Arterial blood pressure was higher in C57-LP offspring than in the other groups. In contrast, ATRAP-Tg-LP offspring did not show an increase in blood pressure compared with NP offspring. Renal angiotensin II type 1 (AT(1)) receptor expression was not altered by maternal malnutrition, whereas angiotensin II type 2 receptor expression was significantly decreased in C57-LP offspring. In conclusion, these findings suggest that a suboptimal intrauterine environment induces adult hypertension because of an alteration of expression of RAS components, which was partly suppressed by sustained ATRAP overexpression via attenuation of the AT(1) receptor-mediated pathological response. PMID:22951100

Tsukuda, Kana; Mogi, Masaki; Iwanami, Jun; Min, Li-Juan; Jing, Fei; Ohshima, Kousei; Horiuchi, Masatsugu

2012-01-01

43

Oxytocin Induces Maternal Behavior in Virgin Female Rats  

Microsoft Academic Search

Intracerebroventricular administration of oxytocin to virgin female rats that had been ovariectomized and primed with estrogen 48 hours previously induced a rapid onset of full maternal behavior. The maternal behavior persisted and its incidence was dose-related. Tocinoic acid, the ring structure of oxytocin, also rapidly induced the onset of persistent, full maternal behavior. Arginine vasopressin induced persistent maternal behavior, but

Cort A. Pedersen; John A. Ascher; Yvonne L. Monroe; Arthur J. Prange

1982-01-01

44

Amelioration of experimental glomerulonephritis by dietary protein restriction  

Microsoft Academic Search

Amelioration of experimental glomerulonephritis by dietary protein restriction. We have examined the effects of various levels of dietary protein intake on the course of nephrotoxic serum nephritis in the rat by feeding low (4.6% casein), standard (23% casein), and high (57.5% casein) protein diets which were identical in calorie, mineral, and electrolyte content. Nephritic rats on a high protein diet

Joel Neugarten; Helen D Feiner; Robert G Schacht; David S Baldwin

1983-01-01

45

Mitochondrial Respiration Is Decreased in Rat Kidney Following Fetal Exposure to a MaternalLow-ProteinDiet  

PubMed Central

Maternal protein restriction in rat pregnancy is associated with impaired renal development and age-related loss of renal function in the resulting offspring. Pregnant rats were fed either control or low-protein (LP) diets, and kidneys from their male offspring were collected at 4, 13, or 16 weeks of age. Mitochondrial state 3 and state 4 respiratory rates were decreased by a third in the LP exposed adults. The reduction in mitochondrial function was not explained by complex IV deficiency or altered expression of the complex I subunits that are typically associated with mitochondrial dysfunction. Similarly, there was no evidence that LP-exposure resulted in greater oxidative damage to the kidney, differential expression of ATP synthetase ?-subunit, and ATP-ADP translocase 1. mRNA expression of uncoupling protein 2 was increased in adult rats exposed to LP in utero, but there was no evidence of differential expression at the protein level. Exposure to maternal undernutrition is associated with a decrease in mitochondrial respiration in kidneys of adult rats. In the absence of gross disturbances in respiratory chain protein expression, programming of coupling efficiency may explain the long-term impact of the maternal diet. PMID:22536494

Engeham, Sarah; Mdaki, Kennedy; Jewell, Kirsty; Austin, Ruth; Lehner, Alexander N.; Langley-Evans, Simon C.

2012-01-01

46

Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring.  

PubMed

Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression. We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group). Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPARalpha gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups. The RF diet prevented these changes. PPARgamma methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPARalpha. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming. PMID:15930441

Lillycrop, Karen A; Phillips, Emma S; Jackson, Alan A; Hanson, Mark A; Burdge, Graham C

2005-06-01

47

Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats.  

PubMed

Substantial evidence suggests that poor intrauterine milieu elicited by maternal nutritional disturbance may programme susceptibility in the fetus to later development of chronic diseases, such as obesity, hypertension, cardiovascular disease and diabetes. One of the most interesting features of fetal programming is the evidence from several studies that the consequences may not be limited to the first-generation offspring and that it can be passed transgenerationally. In the present study, female rats (F0) were fed either a normal-protein diet [control diet (C); 19 g of protein/100 g of diet] or a low-protein diet [restricted diet (R); 5 g of protein/100 g of diet]. The offspring were termed according to the period and the types of diet the dams were fed, i.e. CC, RC, CR and RR (first letter indicates the diet during gestation and the second the diet during lactation). At 3 months of age, F1 females were bred to proven males, outside the experiment, to produce F2 offspring. At weaning, F2 offspring were divided by gender. RC1 offspring (with the number indicating the filial generation) were born with low birthweight, but afterwards they had catch-up growth, reaching the weight of the CC1 offspring. The increased glycaemia in RC1 offspring was associated with insulin resistance. CR1 and RR1 offspring had impaired growth with no changes in glucose metabolism. RC2 offspring had high BM (body mass) at birth, which was sustained over the whole experiment in male offspring. The F2 generation had more alteration in glucose metabolism than the F1 generation. CR2 and RC2 offspring had hyperglycaemia accompanied by hyperinsulinaemia and insulin resistance in both genders. CR2 offspring had an increase in body adiposity with hyperleptinaemia. In conclusion, low protein during gestation improves BM, fat mass and growth rate in F1 rats, but has adverse effects on glucose and leptin metabolism, resulting in insulin resistance in adult F1 and F2 offspring. Low protein during lactation has adverse effects on glucose, insulin and leptin metabolism, resulting in insulin resistance in adult F2 offspring. These findings suggest that low protein during gestation and/or lactation can be passed transgenerationally to the second generation. PMID:17927565

Pinheiro, Alessandra R; Salvucci, Isadora D M; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

2008-03-01

48

MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT  

EPA Science Inventory

MATERNAL AND DEVELOPMENTAL TOXICITY OF PERFLUOROOCTANE SULFONATE IN THE RAT. C. Lau and J.M. Rogers, Reproductive Toxicology Division, NHEERL, ORD, USEPA, Research Triangle Park, NC, USA Perfluorooctane sulfonate (PFOS), an environmentally persistent compound used ...

49

Moderate protein restriction during pregnancy modifies the regulation of triacylglycerol turnover and leads to dysregulation of insulin's anti-lipolytic action.  

PubMed

Moderate protein restriction throughout pregnancy in the rat leads to relative hyperlipidaemia and blunted insulin responsiveness of lipid fuel supply, and impairs foetal growth. The present study examined the basis for these changes. Isocaloric 8% (vs 20%) protein diets were provided throughout pregnancy. Rats were sampled at 19-20 days of gestation. Protein restriction enhanced triacylglycerol (TAG) secretion rates (estimated using Triton WR 1339) 1.6-fold (P < 0.05) in the post-absorptive state. Insulin infusion (4.2 mU/kg per min) decreased plasma TAG concentrations by 33% (P < 0.05) and 48% (P < 0.05) in control (C) and protein-restricted (PR) pregnant groups, an effect associated with suppression of TAG secretion by 42% (P < 0.05) and 51% (P < 0.01) respectively, in the C and PR groups. Since TAG concentrations decline more rapidly, while TAG secretion is enhanced, TAG utilisation during hyperinsulinaemia is enhanced in the PR group. We evaluated whether these changes were associated with dysregulation of lipolysis using adipocytes from two abdominal depots (mesenteric and parametrial). Noradrenaline-stimulated glycerol release was enhanced in parametrial adipocytes (by 40%; P < 0.05) from PR pregnant rats. The anti-lipolytic action of insulin at low concentrations (< or = 15 microU/ml) was impaired by protein restriction (adipocytes from both depots). There was no evidence for altered intra-hepatic regulation of fatty acid (FA) disposal at the level of carnitine palmitoyltransferase. Our results demonstrate increased post-absorptive production of non-carbohydrate energy substrates (TAG and FA) as a consequence of mild protein restriction during pregnancy. These adaptations contribute to a homeostatic strategy to reduce the maternal requirement for gluconeogenesis from available amino acids, optimising the foetal protein supply. Protein restriction also enhances TAG turnover during hyperinsulinaemia. This effect is not a consequence of abnormal regulation of hepatic lipid metabolism by insulin. PMID:9783899

Holness, M J; Fryer, L G; Priestman, D A; Sugden, M C

1998-07-25

50

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

PubMed

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

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

2013-09-01

51

Interaction of maternal separation on the UCh rat cerebellum.  

PubMed

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

2014-01-01

52

The maternal endocrine environment in the low-protein model of intra-uterine growth restriction  

Microsoft Academic Search

Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein\\/kg (v. 200 g\\/kg in the control group)

D. S. Fernandez-Twinn; S. E. Ozanne; S. Ekizoglou; C. Doherty; L. James; B. Gusterson; C. N. Hales

2003-01-01

53

MATERNAL HEPATIC AND EMBRYONIC EFFECTS OF 1,2,4- TRICHLOROBENZENE IN THE RAT  

EPA Science Inventory

The possible maternal hepatic and reproductive effects of 1,2,4-trichlorobenzene (TCB) were assessed in rats given 0, 36, 120, 360, and 1200 mg/kg/day of TCB on Days 9-13 of gestation. The animals were sacrificed on Day 14 of pregnancy. Maternal deaths (2/9 rats 6/6 rats) were re...

54

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

PubMed

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

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

2015-02-01

55

Estrogen Implants in the Medial Preoptic Area Stimulate Maternal Behavior in Male Rats  

Microsoft Academic Search

The present study investigated whether the medial preoptic area (MPOA) mediates estrogen stimulation of maternal behavior in the male as it does in the female. Previous studies have shown that lesions of the medial preoptic area prevent sensitization of maternal behavior in male rats and that in gonadectomized, hormonally primed males, systemically administered estradiol benzoate stimulates short-latency maternal behavior. These

Jay S. Rosenblatt; Kensey Ceus

1998-01-01

56

Involvement of renal corpuscle microRNA expression on epithelial-to-mesenchymal transition in maternal low protein diet in adult programmed rats.  

PubMed

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. PMID:23977013

Sene, Letícia de Barros; Mesquita, Flávia Fernandes; de Moraes, Leonardo Nazário; Santos, Daniela Carvalho; Carvalho, Robson; Gontijo, José Antônio Rocha; Boer, Patrícia Aline

2013-01-01

57

Lactating Rats Retain Nursing Behavior and Maternal Care in Space  

NASA Technical Reports Server (NTRS)

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

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

2001-01-01

58

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

PubMed Central

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

Amarger, Valérie; Lecouillard, Angèle; Ancellet, Laure; Grit, Isabelle; Castellano, Blandine; Hulin, Philippe; Parnet, Patricia

2014-01-01

59

Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats  

Microsoft Academic Search

Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo-2?-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen

Hi-Joon Park; Sabina Lim; Hyang-Sook Lee; Hye-Jung Lee; Yeong-Min Yoo; Hee Jae Lee; Soon Ae Kim; Chang-Shik Yin; Jung-Chul Seo; Joo-Ho Chung

2002-01-01

60

Maternal adrenal hormone secretion mediates behavioural alterations induced by prenatal stress in male and female rats  

Microsoft Academic Search

Prenatal stress in rats has been shown to impair the regulation of the hypothalamic pituitary adrenal (HPA) axis and predispose to anxiogenic and depressive-like behaviour. In a previous study, abolition of excess corticosterone (COR) release during stress by maternal adrenalectomy prevented the dysregulation of the HPA axis. In the present study, we determined whether excess maternal COR is also responsible

Gal Zagron; Marta Weinstock

2006-01-01

61

Effects of maternal iron nutrition during lactation on milk iron and rat neonatal iron status?3  

Microsoft Academic Search

We studied the milk iron content and iron status of lactating rats and their pups to investigatethe relationshipsbetween the iron concentrations of maternal diet and the iron content of milk, and that between the milk iron content and neonatal iron status. Three days after parturition lactating rats were divided into three groups and fed a control (250 ppm iron), a

Sunil G. Anaokar; Philip J. Garry

62

Role of glucocorticoids in programming of maternal diet-induced hypertension in the rat  

Microsoft Academic Search

A rat model of hypertension induced by in utero exposure to maternal low protein diets has previously been described. Low protein exposed rat pups are of lower weight at birth and have large associated placentas. Such animals are proposed, therefore, to mirror individuals in the human population perceived to be at greater risk of cardiovascular disease in adulthood. Recent work

Simon C. Langley-Evans; Gary J. Phillips; David S. Gardner; Alan A. Jackson

1996-01-01

63

Maternal Protein Deficiency Causes Hypermethylation of DNA in the Livers of Rat Fetuses1  

Microsoft Academic Search

Maternal protein deficiency during pregnancy is associated with changes in glucose tolerance and hypertension in the offspring of rats. In this study the growth of rat fetuses was examined when the dams were fed diets containing 18% casein, 9% casein or 8% casein supplemented with threonine. The extra threonine was added to reverse the decrease in circulating threonine concentrations that

William D. Rees; Susan M. Hay; David S. Brown; Christos Antipatis; Robert M. Palmer

64

Maternal low-protein diet suppresses vascular and renal endothelial nitric oxide synthase phosphorylation in rat offspring independent of a postnatal fructose diet.  

PubMed

We investigated the effects of a postnatal fructose diet on the programmed hypertension and vascular and renal dysfunction in offspring from dams exposed to protein restriction. Pregnant Wistar rats were fed control and low-protein diets during the gestation and suckling periods. From the end of lactation, male offspring received standard chow or a 60% fructose diet: a control diet in the gestation and suckling periods and a control diet from the end of lactation, control-on-control (CC), 60% fructose diet-on-control (CF), control-on-low-protein diet (LPC) and 60% fructose diet-on-low-protein diet (LPF). The systolic blood pressure (SBP) was measured during treatment. At postnatal days 94-101, urinary 24 h nitrate/nitrite (NO x ) content, protein levels of endothelial nitric oxide synthase (eNOS) and mRNA levels of endothelin-1 (ET-1), and NAD(P)H oxidase subunits in the aorta and kidney were examined. The SBP at postnatal days 97-101 increased in CF (137 ± 2 mmHg, P < 0.05), LPC (135 ± 1 mmHg, P < 0.05) and LPF (141 ± 2 mmHg, P < 0.05), compared with CC (124 ± 1 mmHg). The urinary NO x contents and eNOS phosphorylation in the aorta and kidney of CF, LPC and LPF decreased when compared with CC. In the aorta, the mRNA levels of NAD(P)H oxidase subunits p47phox in LPC and ET-1 in LPC and LPF increased. These results indicate that maternal protein restriction elevated the blood pressure, the downregulated nitric oxide production and eNOS phosphorylation, whereas the postnatal fructose diet made no significant difference to these alterations. PMID:25141042

Sato, S; Mukai, Y; Norikura, T

2011-06-01

65

Medial Prefrontal Cortex Lesions in the Female Rat Affect Sexual and Maternal Behavior and Their Sequential Organization  

E-print Network

Sexual and maternal behavior in the female rat consists of several stereotyped components, regulated in open-ended, unstructured, or dynamic environments. In rats, lesions of the mPFC produce deficits

Sokolowski, Marla

66

Behavioral and neurobiological studies on the male progeny of maternal rats exposed to chronic unpredictable stress before pregnancy  

Microsoft Academic Search

Studies have shown that maternal chronic stress or depression is linked to an increased risk for affective disorders in progeny. However, the impact of maternal chronic stress before pregnancy on their progeny in animal models has not been well studied. We investigated the behaviors and the neurobiology in 60-day-old male progeny of maternal rats exposed to a 21-day chronic unpredictable

Haihong Li; Lei Zhang; Zeman Fang; Linyun Lin; Cairu Wu; Qingjun Huang

2010-01-01

67

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

1985-01-01

68

Prefrontal-limbic change in dopamine turnover by acupuncture in maternally separated rat pups.  

PubMed

The present study investigated the possible role of acupuncture in alleviating depression-like behavioral changes and examined changes in the levels of serotonin (5-HT), dopamine (DA), and their metabolites in the hippocampus (HP) and prefrontal cortex (PFC) of maternally separated rat pups. On postnatal day 15, rat pups were maternally separated and received acupuncture stimulation at acupoint HT7 or ST36 once a day for 7 days. Then, on postnatal day 21, a tail suspension test was performed, and the HP and PFC were harvested. Levels of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) in the tissue and corticosterone (CORT) in plasma were then measured. The total duration of immobility in maternally separated rat pups increased after maternal separation, and this increase was alleviated by acupuncture stimulation at HT7. The 5-HIAA/5-HT ratio and the levels of 5-HT and 5-HIAA were not significantly changed, but those of the DA and the DOPAC/DA ratio were significantly lower and that of CORT was significantly higher after maternal separation. The maternal separation-induced changes of the DOPAC/DA ratio and the CORT level significantly alleviated after acupuncture stimulation at HT7. These results suppose that the functional recovery of prefrontal-limbic system by acupuncture stimulation plays an important role in acupuncture-induced benefits in this animal model of depression. PMID:22714092

Kwon, Sunoh; Kim, Dongsoo; Park, Hyemee; Yoo, Doyoung; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

2012-10-01

69

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

PubMed

Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014. PMID:24753110

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

2014-04-18

70

IFITM proteins restrict viral membrane hemifusion.  

PubMed

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

Li, Kun; Markosyan, Ruben M; Zheng, Yi-Min; Golfetto, Ottavia; Bungart, Brittani; Li, Minghua; Ding, Shilei; He, Yuxian; Liang, Chen; Lee, James C; Gratton, Enrico; Cohen, Fredric S; Liu, Shan-Lu

2013-01-01

71

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. PMID:23358889

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

2013-01-01

72

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

SciTech Connect

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

Lin, G.W.

1981-01-01

73

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

PubMed

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

Koçkaya, E Arzu; K?l?ç, Aysun

2014-01-01

74

Cisplatin-DNA adduct formation in maternal and fetal rat tissues after transplacental cisplatin exposure.  

PubMed

Cis-diamminedichloroplatinum (II) (cisplatin), given to pregnant rats at 5 mg/kg body weight (bw) is a trans placental carcinogen for fetal liver, kidney, nervous system and lung, resulting in tumor incidences of 22.5, 10.5, 6.1 and 7.5% respectively, in offspring grown to adulthood (B.A. Diwan et al., 1995, Toxicol. Appl. Pharm., 132, 115). In this study, the capacity of cisplatin to pass through the placental barrier and bind covalently to DNA in maternal and fetal tissues was evaluated. Pregnant F344/NCr rats were injected i.p. with single doses of 5, 10 or 15 mg cisplatin/kg bw at 18 days of gestation and sacrificed 24 h later. Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) using both High (90 pmol/micrograms DNA) and Low (0.50 pmol/ microgram DNA) Modified cisplatin-DNA standards and atomic absorbance spectrometry (AAS). The adduct quantities determined by the two DELFIAs varied in concert, but the DELFIA with Low Modified standard gave actual values similar to those observed with AAS. In maternal and fetal tissues, with the exception of placenta in one experiment and maternal kidney in another experiment, the extent of cisplatin-DNA adduct formation increased with dose. In maternal kidney, the low adduct levels observed at the 15 mg/kg dose may reflect kidney toxicity. Fetal kidney, liver and lung contained fewer cisplatin-DNA adducts than the corresponding maternal tissues. In contrast, at 5 and 15 mg/kg, fetal brain DNA contained higher adduct levels than maternal brain DNA. This study demonstrates the presence of DNA damage induced by cisplatin in multiple maternal and fetal rat tissues at tumorigenic doses of drug; the results are therefore consistent with the hypothesis that genotoxic mechanisms play an important role in the drug-induced tumor incidence. PMID:8761423

Giurgiovich, A J; Diwan, B A; Lee, K B; Anderson, L M; Rice, J M; Poirier, M C

1996-08-01

75

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

EPA Science Inventory

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

76

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

EPA Science Inventory

Late Gestational Atrazine Exposure Alters Maternal Nursing Behavior in Rats Jennifer L. Rayner1 and Suzanne E. Fenton2 1 University of North Carolina at Chapel Hill, DESE, Chapel Hill, NC, and 2 USEPA/ ORD/NHEERL/Reproductive Toxicology Division, RTP, NC. At...

77

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

EPA Science Inventory

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

78

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

EPA Science Inventory

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

79

Stress in Neonatal Rats with Different Maternal Care Backgrounds: Monoaminergic and Hormonal Responses.  

PubMed

The first 2 weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin, and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio. HL pups showed higher levels of plasma oxytocin than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin (5-HIAA/5-HT) ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy. PMID:25261216

Henriques, T P; Szawka, R E; Diehl, L A; de Souza, M A; Corrêa, C N; Aranda, B C C; Sebben, V; Franci, C R; Anselmo-Franci, J A; Silveira, P P; de Almeida, R M M

2014-09-27

80

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

EPA Science Inventory

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

81

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...

82

Iron deficiency in the pregnant rat has differential effects on maternal and fetal copper levels  

Microsoft Academic Search

Iron deficiency during pregnancy causes problems both for the mother and fetus. Iron deficiency is known to have secondary effects on copper metabolism. In this study, we use a rat model to examine the effect of iron deficiency on copper levels in maternal and fetal tissue. We assess whether the effects of iron deficiency on copper metabolism are due to

Lorraine Gambling; Susan Dunford; Harry J. McArdle

2004-01-01

83

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.

1986-03-05

84

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

PubMed

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

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

2015-03-01

85

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

2008-01-01

86

Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups  

Microsoft Academic Search

The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase

M. M. Akhavan; M. Emami-Abarghoie; M. Safari; B. Sadighi-Moghaddam; A. A. Vafaei; A. R. Bandegi; A. Rashidy-Pour

2008-01-01

87

Maternal Aggression in Rats: Effects of Olfactory Bulbectomy, ZnSO 4Induced Anosmia, and Vomeronasal Organ Removal  

Microsoft Academic Search

Previous studies from our laboratory indicate that somatosensory inputs to the snout and ventral trunk, but not visual or auditory stimuli, play critical roles in the elicitation and maintenance of maternal aggression by lactating Norway rats toward a strange male intruder. There are conflicting reports on the influence of olfaction on maternal aggression. We explored the possible roles of central

Jane M. Kolunie; Judith M. Stern

1995-01-01

88

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

1998-01-01

89

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

PubMed

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

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

2014-02-01

90

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat.  

PubMed

This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome. PMID:11804852

Coutinho, S V; Plotsky, P M; Sablad, M; Miller, J C; Zhou, H; Bayati, A I; McRoberts, J A; Mayer, E A

2002-02-01

91

The influence of maternal treadmill running during pregnancy on short-term memory and hippocampal cell survival in rat pups  

Microsoft Academic Search

Maternal exercise during pregnancy has been suggested to exert the beneficial effects on the brain functions of offspring. In the present study, we attempted to determine the effects of maternal treadmill running during pregnancy on short-term memory ability, hippocampal cell survival, and the expression of brain-derived neurotrophic factor (BDNF) mRNA in rat pups. After confirming pregnancy, the pregnant rats were

Hong Kim; Sang-Hak Lee; Sung-Soo Kim; Jae-Hyun Yoo; Chang-Ju Kim

2007-01-01

92

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

PubMed

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

Carini, Lindsay M; Nephew, Benjamin C

2013-09-01

93

Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.  

PubMed

Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and mu-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate-putamen nucleus, without any modification for preference to oral morphine consumption. In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and mu-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment. PMID:19553915

Morel, Lydie J; Giros, Bruno; Daugé, Valérie

2009-10-01

94

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

Microsoft Academic Search

Brain vasopressin V1A receptors (V1A-R) and oxytocin receptors (OT-R) are important modulators of social behaviors. We recently showed that exposure to maternal separation (MS; 3 h daily, postnatal days 1–14) induces changes in social behaviors in juvenile and adult male rats. Here, we hypothesize that MS induces brain region-specific changes in V1A-R and OT-R across development, which in turn, may underlie

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

2010-01-01

95

Incorporation of labeled ribonucleic acid precursors into maternal and fetal rat tissues during pregnancy  

SciTech Connect

Tritium-labeled ribonucleic acid precursors, including cytidine, uridine, and orotic acid, were injected into rats with dated pregnancies (14 to 21 days) and virgin rats. The acid-insoluble counts indicating incorporation into fetal and placental tissues showed that the highest incorporation occurred with cytidine, particularly earlier in pregnancy. In contrast, uridine demonstrated a minor degree of incorporation but displayed facile and enhanced transplacental passage with duration of pregnancy as represented by acid-soluble counts. Orotic acid was minimally used by both fetal and placental tissues. The incorporation of labeled precursors into maternal liver, heart, and kidney demonstrated varying responses during the course of pregnancy.

Dorko, M.E.; Hayashi, T.T.

1986-04-01

96

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

PubMed

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

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

2015-01-21

97

Effects of Shiga Toxin Type 2 on Maternal and Fetal Status in Rats in the Early Stage of Pregnancy  

PubMed Central

Shiga toxin type 2 (Stx2), a toxin secreted by Shiga toxin-producing Escherichia coli (STEC), could be one of the causes of maternal and fetal morbimortality not yet investigated. In this study, we examined the effects of Stx2 in rats in the early stage of pregnancy. Sprague-Dawley pregnant rats were intraperitoneally (i.p.) injected with sublethal doses of Stx2, 0.25 and 0.5?ng Stx2/g of body weight (bwt), at day 8 of gestation (early postimplantation period of gestation). Maternal weight loss and food and water intake were analyzed after Stx2 injection. Another group of rats were euthanized and uteri were collected at different times to evaluate fetal status. Immunolocalization of Stx2 in uterus and maternal kidneys was analyzed by immunohistochemistry. The presence of Stx2 receptor (globotriaosylceramide, Gb3) in the uteroplacental unit was observed by thin layer chromatography (TLC). Sublethal doses of Stx2 in rats caused maternal weight loss and pregnancy loss. Stx2 and Gb3 receptor were localized in decidual tissues. Stx2 was also immunolocalized in renal tissues. Our results demonstrate that Stx2 leads to pregnancy loss and maternal morbidity in rats in the early stage of pregnancy. This study highlights the possibility of human pregnancy loss and maternal morbidity mediated by Stx2. PMID:25157355

Sacerdoti, Flavia; Amaral, María M.; Zotta, Elsa; Franchi, Ana M.; Ibarra, Cristina

2014-01-01

98

Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.  

PubMed

Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil also acts as an endocrine disruptor. PMID:24978116

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

2014-01-01

99

Effects of polychlorinated biphenyls on maternal odor conditioning in rat pups.  

PubMed

Polychlorinated biphenyls (PCBs) are pervasive environmental contaminants that can have damaging effects on physiologic, motoric and cognitive function. Results from studies on PCBs and behavior have shown that exposure can alter learning and memory processes and that these shifts in cognitive abilities can be related to changes in hormonal and neural function. Little experimentation has been done on the impact of exposure to PCBs on social and emotional development. Previous work has shown that exposure to PCBs in children can alter play behavior. Importantly, exposure to PCBs has been found to change aspects of maternal-offspring interactions in rodents. The present study examined the impact of PCBs on maternal odor conditioning in rat pups 12-14 days of age. A modified version of the conditioned place preference paradigm was used that incorporated a maternal-associated odor cue (lemon scent) as the conditioned stimulus. PCBs significantly depressed the preference for the maternal-associated cue but did not impair discrimination for a novel odor. These effects could arise due to changes in the social dynamics between the dam and offspring after co-exposure to PCBs. For example, dams exposed to PCBs during gestation have been found to show elevated grooming directed towards pups exposed to PCBs. This change in maternal care can have dramatic effects on behavioral and hormonal systems in the developing rat pup. In conclusion, perinatal PCBs alter important social behaviors of both the mother and pup, and these alterations could have long-lasting effects on behavioral, cognitive and emotional development. PMID:17498760

Cromwell, Howard C; Johnson, Asia; McKnight, Logan; Horinek, Maegan; Asbrock, Christina; Burt, Shannon; Jolous-Jamshidi, Banafsheh; Meserve, Lee A

2007-08-15

100

The effects of adrenalectomy and corticosterone replacement on induction of maternal behavior in the virgin female rat  

E-print Network

­pituitary­adrenal (HPA) axis, which is also activated during stress. The present experiments investigated the effects behavior; Virgin maternal sensitization; Hypothalamic pituitary adrenal axis; Rat Introduction Following evidence to show that corticosterone enhances mother rats' memory for pups during the postpartum period

Sokolowski, Marla

101

Maternal repeated oral exposure to microcystin-LR affects neurobehaviors in developing rats.  

PubMed

Microcystins are toxic peptides secreted by certain water blooms of toxic cyanobacteria. The most widely studied microcystin is microcystin-LR (MC-LR), which exhibits hepatotoxicity and neurotoxicity. However, limited information is available regarding the effects on offspring following maternal exposure. The present study was conducted to observe the effects of progestational exposure to MC-LR on postnatal development in rats. Female Sprague-Dawley rats (28 d old) were randomly divided into a control group and 3 treatment groups (1.0?µg MC-LR/kg body wt, 5.0?µg MC-LR/kg body wt, and 20.0?µg MC-LR/kg body wt), with 7 rats per group. The MC-LR was administered through gavage once every 48?h for 8 wk. Pure water was used as control. Each female rat was mated with an unexposed adult male rat. Motor development, behavioral development, and learning ability of pups were detected using surface righting reflex, negative geotaxis, and cliff avoidance tests on postnatal day 7. Open-field and Morris water maze tests were performed on postnatal day 28 and day 60. The levels of lipid peroxidation products and antioxidant indices in the rat hippocampus were also detected. Pups from the MC-LR-treated groups had significantly lower scores than controls in the cliff avoidance test (p?maternal exposure to MC-LR has adverse effects on neurodevelopment in rat offspring. PMID:25319481

Li, XiaoBo; Zhang, Xin; Ju, Jingjuan; Li, Yunhui; Yin, Lihong; Pu, Yuepu

2015-01-01

102

Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model  

PubMed Central

Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic activities (EMG). NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3 g/kg and 1.5 g/kg per day) for seven days resulted in an increase in the pain threshold (NMS control: 19.1 ± 1.0 mmHg vs low-dose: 24.8 ± 1.3 mmHg and high-dose: 25.2 ± 1.8 mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952 ± 202 in NMS control group vs 1074 ± 90 in low-dose group and 1145 ± 92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT3 receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat. PMID:22230486

Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul SP; Wu, Justin CY; Lao, Lixing; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Yeung, John HK; Che, Chun-Tao

2012-01-01

103

Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy  

PubMed Central

It has been suggested that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy. However, we have reported a selective increase in renal inner medullary PDE5 that participates in the sodium retention of pregnancy. Therefore, the purpose of this study was to determine whether oral sildenafil treatment impairs maternal plasma volume expansion and/or fetal growth during rat pregnancy. Rats received sildenafil (10 mg·kg?1·day?1, 50 mg·kg?1·day?1, or 90 mg·kg?1·day?1) or vehicle on days 4–20 of pregnancy. On days 14–19, rats were housed in metabolic cages for collection of urine and measurement of food and water intake. Terminal hemodynamic and fetal measurements were taken on day 20. None of the sildenafil doses lowered blood pressure, and although all doses increased plasma cGMP concentrations, only the highest dose increased aortic and inner medullary cGMP content. Sildenafil had no effect on maternal weight gain; however, the highest dose decreased both plasma volume and renal sodium retention. The pup number and size were similar among the groups. Therefore, these studies suggest that low doses of systemic sildenafil may be safe during pregnancy in the rat, but higher doses may interfere with the physiological sodium retention and volume expansion of pregnancy. The effects of systemic sildenafil on blood pressure and sodium retention during hypertension in human pregnancy remain to be examined. PMID:19955496

Baylis, Chris

2010-01-01

104

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.

2001-01-01

105

Periaqueductal gray ? and ? opioid receptors determine behavioral selection from maternal to predatory behavior in lactating rats.  

PubMed

Every mother must optimize her time between caring for her young and her subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a critical site that modulates the switch between maternal and predatory behavior. Opioids play multiple roles in both maternal behavior and this switching process. The present study used a pharmacological approach to evaluate the functional role of rlPAG ? and ? opioid receptors in behavioral selection. Rat dams were implanted with a guide cannula in the rlPAG and divided into three experiments in which we tested the role of opioid agonists (Experiment 1), the influence of ? and ? opioid receptor blockade in the presence of morphine (Experiment 2), and the influence of ? and ? opioid receptor blockade (Experiment 3). After behavioral test, in Experiment 4, we evaluated rlPAG ? and ? receptor activation in all Experiments 1-3. The results showed that massive opioidergic activation induced by morphine in the rlPAG inhibited maternal behavior without interfering with predatory hunting. No behavioral changes and no receptor activation were promoted by the specific agonist alone. However, ? receptor blockade increased hunting behavior and increased the level of ? receptor activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by a functional interaction between opioid receptor subtypes. Such a compensatory receptor interaction appears to be relevant for behavioral selection among motivated behaviors. These findings indicate a role for multiple opioid receptor interactions in the modulation of behavioral selection between maternal and predatory behaviors in the PAG. PMID:25116253

Klein, Marianne Orlandini; Cruz, Aline de Mello; Machado, Franciele Corrêa; Picolo, Gisele; Canteras, Newton Sabino; Felicio, Luciano Freitas

2014-11-01

106

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.

1986-10-01

107

The effects of Love Canal soil extracts on maternal health and fetal development in rats.  

PubMed

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. PMID:3781137

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

1986-10-01

108

Retarded development of noenatal rat lung by maternal malnutrition.  

PubMed

Inadequate dietary intake during late pregnancy may have significant effects on the developing fetal lung which undergoes rapid cellular multiplication and differentiation shortly before birth. The morphology, glycogen distribution and acid phosphatase activity in normal and starved neonatal rats have been studied sequentially, by using histochemical and cytochemical methods. It has been shown that the normal pattern of lung growth and enzymatic development is retarded in neonates of malnourished mothers. A slowed rate of cellular division and differentiation in the critical prenatal period resulted in a more immature air-blood barrier at birth, with glycogen retention by some epithelial cells. Delayed Type 2 cell maturation with diminished acid phosphatase activity suggests a decrease in surfactant production in the malnourished newborn. In addition, fewer alveolar macrophages with reduced acid phosphatase activity were observed in the perinatal period of starved rats; this finding might have implications for the handling of inhaled bacteria shortly after birth. These results indicate that nutritional status of the mother has a marked effect on fetal lung growth and development by inhibiting cellular proliferation, differentiation and enzyme development by epithelial and macrophagic cells. PMID:659840

Curle, D C; Adamson, I Y

1978-05-01

109

2-Arachidonoylglycerol into the lateral hypothalamus improves reduced sleep in adult rats subjected to maternal separation.  

PubMed

We have previously reported that maternal separation (MS) for 3 h daily during the first two postnatal weeks increases wakefulness, whereas it reduces sleep in rats. Oleamide, an agonist of the cannabinoid receptor type 1, increases sleep in MS rats to such a level that we cannot differentiate their sleep patterns from those of their non-MS (NMS) siblings. However, 2-arachidonoylglycerol (2-AG), an endocannabinoid, infused into the lateral hypothalamus of NMS rats at the beginning of the dark phase of the cycle increases rapid eye movement sleep and the expression of c-Fos on the rapid eye movement sleep promoting melanin-concentrating hormone neurons. We recorded the sleep-wake cycle of adult rats subjected to MS for 3 h daily from postnatal days 2 to 16, as well as in their NMS siblings. Besides the electrodes for recording the sleep-wake cycle, a couple of cannulae aimed bilaterally to the lateral hypothalamus were implanted to infuse 2-AG. We found that administration of 2-AG into the lateral hypothalamus of MS rats at the beginning of the light phase of the cycle restores sleep, whereas sleep and wakefulness of NMS rats under 2-AG infusion do not show any significant change. PMID:25356522

Pérez-Morales, Marcel; Fajardo-Valdez, Alfonso; Méndez-Díaz, Mónica; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

2014-12-17

110

Vasopressin deficiency diminishes acute and long-term consequences of maternal deprivation in male rat pups.  

PubMed

Early life events have special importance in the development as postnatal environmental alterations may permanently affect the lifetime vulnerability to diseases. For the interpretation of the long-term consequences it is important to understand the immediate effects. As the role of vasopressin in hypothalamic-pituitary-adrenal axis regulation as well as in affective disorders seem to be important we addressed the question whether the congenital lack of vasopressin will modify the stress reactivity of the pups and will influence the later consequences of single 24h maternal deprivation (MD) on both stress-reactivity and stress-related behavioral changes. Vasopressin-producing (di/+) and deficient (di/di) Brattleboro rat were used. In 10-day-old pups MD induced a remarkable corticosterone rise in both genotypes without adrenocorticotropin (ACTH) increase in di/di rats. Studying the later consequences at around weaning (25-35-day-old rats) we found somatic and hormonal alterations (body weight reduction, dysregulation of the stress axis) which were not that obvious in di/di rats. The more anxious state of MD rats was not detectable in di/di rats both at weaning and in adulthood (7-12-week-old). The lack of vasopressin abolished all chronic stress and anxiety-like tendencies both at weaning and in adulthood probably as a consequence of reduced ACTH rise immediately after MD in pups. This finding suggests that postnatal stress-induced ACTH rise may have long-term developmental consequences. PMID:25462910

Zelena, Dóra; Stocker, Berhard; Barna, István; Tóth, Zsuzsanna E; Makara, Gábor B

2015-01-01

111

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. PMID:24895554

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

2014-01-01

112

Impaired adaptation of gastrointestinal motility following chronic stress in maternally separated rats.  

PubMed

Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats. PMID:22241856

Bülbül, Mehmet; Babygirija, Reji; Cerjak, Diana; Yoshimoto, Sazu; Ludwig, Kirk; Takahashi, Toku

2012-04-01

113

Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines  

Microsoft Academic Search

Aims\\/hypothesis  A maternal low-protein diet has been shown to induce an increased susceptibility of fetal islets to cytokines, but this effect can be avoided by maternal taurine supplementation. Here, we question whether these effects persist until adulthood in the offspring, despite the animal having a normal diet after weaning.Methods  Pregnant Wistar rats received a diet of either 20% or 8% protein (control

S. Merezak; B. Reusens; A. Renard; K. Goosse; L. Kalbe; M. T. Ahn; J. Tamarit-Rodriguez; C. Remacle

2004-01-01

114

Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low protein diet  

Microsoft Academic Search

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet)

Wing Yee Kwong; Daniel J Miller; Elizabeth Ursell; Arthur E Wild; Adrian P Wilkins; Clive Osmond; Fred W Anthony; Tom P Fleming

2006-01-01

115

Dopamine D1 Receptor Stimulation of the Nucleus Accumbens or the Medial Preoptic Area Promotes the Onset of Maternal Behavior in Pregnancy-Terminated Rats  

Microsoft Academic Search

There is good evidence that interference with the mesolimbic dopamine (DA) system results in impaired maternal responding in postpartum female rats. However, whether activation of the mesolimbic DA system is capable of promoting maternal behavior has not been investigated. This study examined whether increasing DA activity in various brain regions of pregnancy-terminated, naive female rats would stimulate the onset of

Danielle S. Stolzenberg; Jonathan B. McKenna; Samantha Keough; Rebecca Hancock; Marilyn J. Numan; Michael Numan

2007-01-01

116

Oleamide restores sleep in adult rats that were subjected to maternal separation.  

PubMed

Maternal separation (MS) induces a series of changes in rats' behavior; among them a reduction in spontaneous sleep. One potentially impaired system is the endocannabinoid system (eCBs), since it contributes to generate sleep. To investigate if there are situations early in life that affect the eCBs, which would contribute to make rats vulnerable to suffering insomnia, we studied the rodent model of MS. Rats were separated from their mothers for 3h-periods daily, from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult rats), they were implanted with electrodes to record the sleep-waking cycle (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R), OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1 receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the consequent increase in waking (W) as compared to NMS siblings. OLE normalized the SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R expression and OLE improves sleep in adult rats. PMID:22975223

Reyes Prieto, Nidia M; Romano López, Antonio; Pérez Morales, Marcel; Pech, Olivia; Méndez-Díaz, Mónica; Ruiz Contreras, Alejandra E; Prospéro-García, Oscar

2012-12-01

117

Decreased amount of ovarian tissue and maternal age affect embryonic development in old rats.  

PubMed

The effects of addition and/or reduction of ovarian tissue and maternal age on ovulation rates (number of corpora lutea) and embryonic development were evaluated in old, regularly cycling rats on Days 4 and 11 of gestation. Young and old control rats and old rats which were either unilaterally ovariectomized (ULO), intact with 2 additional ovaries transplanted under the kidney capsule or ULO with 2 additional ovaries transplanted under the kidney capsule were mated on proestrus of a 4- or 5-day cycle between the 3rd and 9th postoperative cycle. The percentages of normal embryos on Days 4 and 11 of gestation were decreased (P less than 0.05) in the ULO rats, while on a per ovary basis the ovulation rate and ovarian weight were significantly increased in all the ULO rats compared to the old intact rats. An increase in abnormal and retarded embryos each contributed to this decreased percentage of normal Day 4 and Day 11 embryos in the ULO rats (P less than 0.05). Transplantation of ovarian tissue into old intact and ULO rats did not affect either the ovulation rate or the percentage of normal embryos and did not reverse the detrimental effects of unilateral ovariectomy. This could be due to inadequate stimulation or function of the ovarian tissue remaining in the transplants and may arise from a smaller vascular bed and limited blood flow to the transplants. Although regularly cycling young and old control rats had similar ovulation rates, the old control animals had a decreased percentage of normal embryos on Day 11 of gestation, but not on Day 4 of gestation, compared to the young control rats. This decrease in percentage of normal Day 11 embryos in the old intact rats was due mainly to an increase in retarded rather than abnormal embryos. From this study, it is concluded that unilateral ovariectomy of old cycling rats was detrimental to embryonic development. A similar, but more gradual decrease in functional ovarian tissue with aging, could cause the increased incidence of anomalies in embryos of older females. PMID:7126742

Sopelak, V M; Butcher, R L

1982-09-01

118

Increased BOLD Activation to Predator Stressor in Subiculum and Midbrain of Amphetamine-Sensitized Maternal Rats  

PubMed Central

Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5 ?L TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1 mg/kg, i.p. X 3 days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized, but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. PMID:21134359

Febo, Marcelo; Pira, Ashley S.

2011-01-01

119

Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring.  

PubMed

Pentaerythritol tetranitrate is devoid of nitrate tolerance and shows no reproductive or developmental toxicity in animal studies. Recently, pentaerythritol tetranitrate has been demonstrated to reduce the risk of intrauterine growth restriction and the risk of preterm birth in women with abnormal placental perfusion. This study was conducted to test the perinatal programming effect of pentaerythritol tetranitrate in spontaneously hypertensive rats, a rat model of genetic hypertension. Parental spontaneously hypertensive rats were treated with pentaerythritol tetranitrate (50 mg/kg per day) during pregnancy and lactation periods; the offspring received standard chow without pentaerythritol tetranitrate after weaning. Maternal treatment with pentaerythritol tetranitrate had no effect on blood pressure in male offspring. In the female offspring, however, a persistent reduction in blood pressure was observed at 6 and 8 months. This long-lasting effect was accompanied by an upregulation of endothelial nitric oxide synthase, mitochondrial superoxide dismutase, glutathione peroxidase 1, and heme oxygenase 1 in the aorta of 8-month-old female offspring, which was likely to result from epigenetic changes (enhanced histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation) and transcriptional activation (enhanced binding of DNA-directed RNA polymerase II to the transcription start site of the genes). In organ chamber experiments, the endothelium-dependent, nitric oxide-mediated vasodilation to acetylcholine was enhanced in aorta from female offspring of the pentaerythritol tetranitrate-treated parental spontaneously hypertensive rats. In conclusion, maternal pentaerythritol tetranitrate treatment leads to epigenetic modifications, gene expression changes, an improvement of endothelial function and a persistent blood pressure reduction in the female offspring. PMID:25385760

Wu, Zhixiong; Siuda, Daniel; Xia, Ning; Reifenberg, Gisela; Daiber, Andreas; Münzel, Thomas; Förstermann, Ulrich; Li, Huige

2015-01-01

120

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

PubMed

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. PMID:23781346

Garbrecht, Mark R; Lamb, Fred S

2013-01-01

121

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. PMID:23781346

Garbrecht, Mark R.; Lamb, Fred S.

2013-01-01

122

Effects of maternal exposure to the galactagogue Sulpiride on reproductive parameters in female rats.  

PubMed

The antipsychotic Sulpiride has been documented as an effective galactagogue that acts blocking dopamine receptors, increasing prolactin concentrations. However, this drug passes through the milk exposing neonates during postnatal development, which may result in functional and morphological alterations in adult life. Therefore, the aim of this study was to investigate whether maternal exposure to Sulpiride during lactation could impair reproductive development of female offspring. The dams were treated daily by gavage with Sulpiride doses of 2.5mg/Kg (SUL 2.5mg group) and 25mg/Kg (SUL 25mg group), or distilled water (Control group) throughout the lactation period. During early life, body weight, anogenital distance, and vaginal opening were analyzed on the female offspring. In adulthood, estrous cycle, sexual behavior, estrogen levels as well as the weight of the reproductive organs were evaluated. There were no differences regarding body weight, anogenital distance, puberty onset, frequency and duration of the estrous cycle and estradiol levels on female offspring. Nonetheless, there were changes in sexual behavior. There was an increase in the number of observations in reflex magnitude 0 (absence of lordosis) and reflex magnitude 2 as well as a reduction of reflex magnitude 3 in the rats of SUL 25mg group in relation to the Control group, suggesting a decrease in sexual receptivity of these animals. These results demonstrate that maternal exposure to Sulpiride can alter reproductive function in female offspring rats. PMID:25554483

de Azevedo Camin, Nathália; Vieira, Milene Leivas; Montagnini, Bruno Garcia; Kiss, Ana Carolina Inhasz; Gerardin, Daniela Cristina Ceccatto

2015-03-01

123

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

PubMed

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

2013-02-01

124

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

2007-01-01

125

Rats with Hypertension Induced by in utero Exposure to Maternal Low-Protein Diets Fail to Increase Blood Pressure in Response to a High Salt Intake  

Microsoft Academic Search

Hypertension in the rat has been demonstrated to be determined in utero by exposure to maternal low-protein diets. Assessment was made of the response of rats with maternal diet-induced hypertension to a chronic high intake of sodium chloride. Normotensive and hypertensive animals were provided with either drinking water (control) or 1.5% sodium chloride over a 7-day period. Normotensive rats significantly

Simon C. Langley-Evans; Alan A. Jackson

1996-01-01

126

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

PubMed

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. The rats were killed 2 weeks later, at postnatal day 74. Their brains were dissected and the hippocampus rapidly removed for proteomic analysis by isobaric tagging (iTRAQ) and quantification of peptides by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS). Maternal separation upregulated hippocampal proteins functionally involved in energy metabolism (nucleoside diphosphate kinase B, enolase and triosephosphate isomerase) and synaptic plasticity (?-synuclein, tenascin-R, Ba1-667, brevican and neurocan core protein) in the non-lesioned hemisphere. Exercise reversed many of these changes by downregulating the levels of hippocampal proteins functionally associated with energy metabolism (nucleoside diphosphate kinase B, enolase and triosephosphate isomerase) and synaptic plasticity (?-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 partly to reverse the effects of maternal separation stress on these proteins in the non-lesioned hemisphere. The partial reversal of maternal separation-induced proteins by exercise in the non-lesioned side sheds some insight into the mechanism by which exercise alters the molecular role players involved in determining the consequences of early life stress. PMID:22636255

Dimatelis, J J; Hendricks, S; Hsieh, J; Vlok, N M; Bugarith, K; Daniels, W M U; Russell, V A

2013-01-01

127

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

PubMed

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

Sanders, Brian J; Anticevic, Alan

2007-10-01

128

Effect of maternal fluoride exposure on developing CNS of rats: Protective role of Aloe vera , Curcuma longa and Ocimum sanctum  

Microsoft Academic Search

Fluoride is toxic to neuronal development and its excessive intake during pregnancy cause adverse effects on neonatal development. The present study examined the presence of oxidative stress during maternal exposure of fluoride and the therapeutic strategy of Aloe vera, Curcuma longa and Ocimum sanctum extracts in functional prevention of fluoride led oxidative stress. The pregnant Wistar rats were exposed to

N Madhusudhan; P Mahaboob Basha; Puja Rai; Fiyaz Ahmed; G Ravi Prasad

2010-01-01

129

Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets  

Microsoft Academic Search

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Maternal-diet-induced hypertension has been previously associated with elevated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is investigated. Pulmonary and

Simon C. Langley-Evans; Alan A. Jackson

1995-01-01

130

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. PMID:22983352

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

2012-01-01

131

Placental Lactogen Administration Reverses the Effect of Low-Protein Diet on Maternal and Fetal Serum Somatomedin Levels in the Pregnant Rat  

Microsoft Academic Search

Female rats were studied on day 20 of pregnancy after being fed either a 5% lactalbumin (low protein) diet or a 20% lactalbumin (adequate) diet for the last 2 weeks of pregnancy. Rats on the lower intake of protein showed decreased serum levels of rat placental lactogen and reduced numbers of lactogenic receptors in the maternal liver. These changes were

S. J. Pilistine; A. C. Moses; H. N. Munro

1984-01-01

132

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. PMID:23300784

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

2012-01-01

133

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

PubMed

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

2013-08-01

134

Maternal and Fetal Blood and Organ Toluene Levels in Rats Following Acute and Repeated Binge Inhalation Exposure  

PubMed Central

Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8,000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites of action throughout the maternal-placental-fetal unit. PMID:17669620

Bowen, Scott E.; Hannigan, John H.; Irtenkauf, Susan

2007-01-01

135

Effects of essential oil from Chamaecyparis obtusa on cytokine genes in the hippocampus of maternal separation rats.  

PubMed

We investigated the effects of an essential oil from Chamaecyparis obtusa (EOCO) on early life stress, using maternal separation (MS) rats and a microarray method to analyze the changes in gene expressions caused by EOCO in the hippocampus of MS rats. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared with the untreated MS rats in the elevated plus-maze (EPM) test. In the microarray analysis, we found that EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and also confirmed that using reverse transcriptase - PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, protein expression was also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulates cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats. PMID:24502631

Park, Hae Jeong; Kim, Su Kang; Kang, Won Sub; Woo, Jong-Min; Kim, Jong Woo

2014-02-01

136

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

PubMed

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

2014-08-01

137

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. PMID:25006477

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

2014-01-01

138

Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation.  

PubMed

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life. PMID:25102263

Bai, S Y; Briggs, D I; Vickers, M H

2012-10-01

139

Maternal green tea extract supplementation to rats fed a high-fat diet ameliorates insulin resistance in adult male offspring.  

PubMed

Maternal overnutrition is associated with increased risk of metabolic disorders in the offspring. This study tested the hypothesis that maternal green tea (GT) supplementation can alleviate metabolic derangements in high-fat-diet-fed rats born of obese dams. Female Sprague-Dawley rats were fed low-fat (LF, 7%), high-fat (HF, 30%) or HF diet containing 0.75% or 1.0% GT extract (GT1, GT2) prior to conception and throughout gestation and lactation. Both doses of GT significantly improved metabolic parameters of HF-fed lactating dams (P<.05). Birth weight and litter size of offspring from HF dams were similar, but GT supplementation led to lighter pups on day 21 (P<.05). The weaned male pups received HF, GT1 or GT2 diet (dam/pup diet groups: LF/HF, HF/HF, HF/GT1, HF/GT2, GT1/HF and GT2/HF). At week 13, they had similar weight but insulin resistance index (IRI), serum nonesterified fatty acid (NEFA) and liver triglyceride of rats born to GT dams were 57%, 23% and 26% lower, accompanied by improved gene/protein expressions related to lipid and glucose metabolism, compared with the HF/HF rats (P<.05). Although HF/GT1 and HF/GT2 rats had lower serum NEFA, their insulin and IRI were comparable to HF/HF rats. This study shows that metabolic derangements induced by an overnourished mother could be offset by supplementing GT to the maternal diet and that this approach is more effective than giving GT to offspring since weaning. Hence, adverse effects of developmental programming are reversible, at least in part, by supplementing bioactive food component(s) to the mother's diet. PMID:22464150

Li, Shiying; Tse, Iris M Y; Li, Edmund T S

2012-12-01

140

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

PubMed

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

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

2014-09-01

141

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats  

PubMed Central

AIM: To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms. METHODS: JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method. RESULTS: NMS treatment significantly reduced pain threshold pressure (37.4 ± 1.4 mmHg), as compared to that of NH rats (57.7 ± 1.9 mmHg, P < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 ± 0.9 mmHg vs 52.8 ± 2.3 mmHg in the high dose group, 40.2 ± 1.6 mmHg vs 46.5 ± 1.3 mmHg in the middle dose group, and 39.3 ± 0.7 mmHg vs 46.5 ± 1.6 mmHg in the low dose group, P < 0.05). Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean ?AUC values were: 0.17 ± 0.03, 0.53 ± 0.15, 1.06 ± 0.18, 1.22 ± 0.24 in the high dose group; 0.23 ± 0.04, 0.68 ± 0.17, 1.27 ± 0.26, 1.8 ± 0.3 in the middle dose group; and 0.29 ± 0.06, 0.8 ± 0.16, 1.53 ± 0.24, 2.1 ± 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared to the NMS vehicle group. The mean ?AUC values were: 0.57 ± 0.12, 1.33 ± 0.18, 2.57 ± 0.37, 3.08 ± 0.37 for the pressures 20, 40, 60, 80 mmHg (P < 0.05). JCM-16021 treatment significantly reduced the 5-HT concentrations (from high, middle and low dosage groups: 60.25 ± 5.98 ng/100 mg, 60.32 ± 4.22 ng/100 mg, 73.31 ± 7.65 ng/100 mg), as compared to the NMS vehicle groups (93.11 ± 9.85 ng/100 mg, P < 0.05); and increased the 5-HIAA concentrations (after treatment, from high, middle and low dosage groups: 54.24 ± 3.27 ng/100 mg, 50.34 ± 1.26 ng/100 mg, 51.37 ± 2.13 ng/100 mg) when compared to that in the NMS vehicle group (51.75 ± 1.98 ng/100 mg, P < 0.05); but did not change the enterochromaffin cell numbers in the colon of rats. In addition, NMS rats had higher SERT expression (n = 10) than NH rats (n = 8, P < 0.05). JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group (P < 0.01-0.001). CONCLUSION: JCM-16021 can attenuate visceral hypersensitivity, and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats. PMID:20143462

Bian, Zhao-Xiang; Zhang, Man; Han, Quan-Bin; Xu, Hong-Xi; Sung, Joseph JY

2010-01-01

142

Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms.  

PubMed

Animal models support human epidemiological studies in demonstrating a relationship between impaired fetal growth and risk of adult hypertension. Undernutrition during pregnancy exerts programming effects on the developing kidney, and modulation of angiotensin receptor (ATR) expression has been observed persisting into adult life. Fetal overexposure to glucocorticoids is thought to be central to the nutritional programming of blood pressure and may act through an interaction with ATR expression. Pregnant female Wistar rats were fed a control (n = 6) or a maternal low-protein diet (MLP; n = 17) throughout pregnancy. The glucocorticoid dependency of MLP effects was tested using metyrapone, an inhibitor of corticosterone synthesis. MLP-fed rats were injected twice daily with metyrapone, metyrapone plus corticosterone, or vehicle over days 1-14 of pregnancy. At delivery, all animals were fed standard laboratory chow. MLP-exposed offspring 4 wk of age exhibited increased systolic blood pressure compared with controls (P < 0.05), which proved to be glucocorticoid dependent in males only. AT(1)R mRNA expression was independent of in utero dietary treatment. AT(2)R mRNA expression was downregulated in MLP-exposed females only (P < 0.05) and in a glucocorticoid-independent manner. Male offspring exhibited glucocorticoid-dependent hypertension with no modulation of renal ATR mRNA expression. In contrast, female offspring exhibited glucocorticoid-independent hypertension associated with reduced expression of renal AT(2)R mRNA. These data do not support the hypothesis that an interaction between glucocorticoid and ATR mRNA expression underlies the nutritional programming of blood pressure but instead suggest two independent mechanisms acting in a sex-specific manner. PMID:15374820

McMullen, Sarah; Langley-Evans, Simon C

2005-01-01

143

Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment  

PubMed Central

Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

2014-01-01

144

Effects of maternal separation on behavior and brain damage in adult rats exposed to neonatal hypoxia-ischemia.  

PubMed

Animal studies suggest that maternal separation, a widely used paradigm to study the effects of early life adversity, exerts a profound and life-long impact on both brain and behavior. The aim of the current study was to investigate whether adverse early life experiences interact with neonatal hypoxia-ischemia, affecting the outcome of this neurological insult at both functional and structural levels during adulthood. Rat pups were separated from their mothers during postnatal days 1-6, for either a short (15 min) or prolonged (180 min) period, while another group was left undisturbed. On postnatal day 7, a subgroup from each of the three postnatal manipulations was exposed to a hypoxic-ischemic episode. Behavioral examination took place approximately at three months of age and included tests of learning and memory (Morris water maze, novel object and novel place recognition), as well as motor coordination (rota-rod). We found that both prolonged maternal separation and neonatal hypoxia-ischemia impaired the animals' spatial learning and reference memory. Deficits in spatial but not visual recognition memory were detected only in hypoxic-ischemic rats. Interestingly, prolonged maternal separation prior to neonatal hypoxia-ischemia augmented the reference memory impairments. Histological analysis of infarct size, hippocampal area and thickness of corpus callosum did not reveal any exacerbation of damage in hypoxic-ischemic rats that were maternally separated for a prolonged period. These are the first data suggesting that an adverse postnatal environmental manipulation of just 6 days causes long-term effects on spatial learning and memory and may render the organism more vulnerable to a subsequent insult. PMID:25433094

Tata, Despina A; Markostamou, Ioanna; Ioannidis, Anestis; Gkioka, Mara; Simeonidou, Constantina; Anogianakis, Georgios; Spandou, Evangelia

2015-03-01

145

Maternal weight as an alternative determinant of the gestational day of Wistar rats housed in individually-ventilated cages.  

PubMed

One of the commonly used animal models in fertility, developmental and neurobiological studies is the laboratory rat. The early recognition of rat pregnancy and confirmation of the exact embryonic day are vital. The aim of this study was to investigate the correlation of maternal weight at the time of conception to its increase throughout gestation, aiming to develop a mathematical model, which can be used for the determination of the exact day of pregnancy, set the threshold, and monitor pregnancy from the onset. We studied a total of 173 Wistar rats with a mean body weight of 238.22?±?34.9?g. After 72?h at the male's cages, we considered as Day 0 (D0) the day in which a copulatory plug or sperm was found during the vaginal smear examination. After that period the female animals were transferred into their cages, and weight monitoring started 14 days (D14) after D0, until parturition. Based on the statistical analysis, there is a correlation between maternal body weight at D0 and maternal body weight from D14 to D19. Moreover, the average weight gain from D14 to D19 is positively correlated to initial female body weight, while there is no correlation between each pregnant animal's weight from D14 to D19 and litter size. A mathematical model was developed as a tool for the verification of the day of pregnancy. In conclusion, continuous monitoring of maternal weight after D14 can be a reliable method for the recognition of pregnancy and determination of the exact gestational day. PMID:25488321

Paronis, E; Samara, A; Polyzos, A; Spyropoulos, C; Kostomitsopoulos, N G

2014-12-01

146

Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low protein diet.  

PubMed

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself. PMID:16885535

Kwong, Wing Yee; Miller, Daniel J; Ursell, Elizabeth; Wild, Arthur E; Wilkins, Adrian P; Osmond, Clive; Anthony, Fred W; Fleming, Tom P

2006-08-01

147

Effects of maternal deprivation and the duration of reunion time on rat pup ultrasonic vocalization responses to isolation: Possible implications for human infant studies.  

PubMed

In a paradigm that may serve as a translational model for maternal separation experiences of human infants in neonatal intensive care units, we examined how the duration of reunion with the dam influenced the phenomenon of maternal potentiation of ultrasonic vocalizations, in which isolated rat pups increase rates of vocalization following brief interactions with dams. We report that maternal potentiation in 12-13 day-old rats did not occur after reunions with their anesthetized dam that lasted longer than 15-min. However, after 18?hr maternal separation, isolated pups given reunions with their anesthetized dam increased vocalization rate even with reunions as long as 3?hr. Using a split-cage apparatus that prevented physical contact, the impact of 18?hr separations on maternal potentiation was partially offset by experiencing olfactory and/or auditory stimuli of the mother. These results suggest that maintaining partial maternal sensory exposure during prolonged maternal separation can reduce responses elicited by subsequent maternal separation. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 63-72, 2015. PMID:25380197

Shair, Harry N; Rupert, Deborah D; Rosko, Lauren M; Hofer, Myron A; Myers, Michael M; Welch, Martha G

2015-01-01

148

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

PubMed Central

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

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

2001-01-01

149

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: amronco@inta.cl [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)

2011-03-01

150

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny.  

PubMed

Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6?mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial ?-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TR?1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues. PMID:25653393

Lisboa, P C; de Oliveira, E; Manhães, A C; Santos-Silva, A P; Pinheiro, C R; Younes-Rapozo, V; Faustino, L C; Ortiga-Carvalho, T M; Moura, E G

2015-03-01

151

The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum rat  

E-print Network

The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum of ``normal'' behaviors. The present studies investigated the effects of adrenalectomy and of varying pregnancy were adrenalectomized or given sham surgeries and were tested for maternal behavior. In the first

Sokolowski, Marla

152

Early Maternal Separation Increases Symptoms of Activity-Based Anorexia in Male and Female Rats  

Microsoft Academic Search

Running activates the hypothalamic–pituitary–adrenal (HPA) axis, increasing the release of stress hormones known to exert anorexic effects. HPA axis reactivity is strongly influenced by early postnatal manipulations, including removal of pups from the dam for short (handling) or prolonged (maternal separation) durations during the preweaning period. The authors examined the effects of handling and maternal separation on food intake, body

Stephanie Hancock; Virginia Grant

2009-01-01

153

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

PubMed Central

BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and ?Cue). The BOLD response to +Cue and ?Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus ?Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

Caffrey, Martha K.; Febo, Marcelo

2013-01-01

154

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))

1991-03-15

155

Maternal dexamethasone and GLP-2 have early effects on intestinal sugar transport in their suckling rat offspring.  

PubMed

Both glucagon-like peptide 2 (GLP-2) and glucocorticosteroids enhance intestinal uptake in mature animals. Maternal stimuli may cause intestinal adaptation in the offspring. We hypothesized that administering GLP-2, dexamethasone (DEX) or a combination of GLP-2+DEX to rat dams during pregnancy and lactation would enhance intestinal sugar uptake in their offspring. Rat dams were treated with GLP-2 (0.1 microg/g/day), DEX (0.128 microg/g/day), a combination of GLP-2+DEX or placebo. Glucose and fructose uptake was assessed in their suckling offspring using an in vitro intestinal ring uptake technique. The protein abundance of SGLT1, GLUT5, GLUT2, Na(+)K(+)-ATPase and selected signals was determined by immunohistochemistry; GLP-2 caused hypertrophy of the jejunal enterocytes and increased ileal villous height. Jejunal fructose uptake was reduced by GLP-2, DEX and GLP-2+DEX. V(max) for jejunal glucose uptake was reduced with DEX and GLP-2+DEX. These declines were not explained by alterations in transporter abundance. Decreases in Akt and mTOR abundance were associated with declines in transporter activity. We speculate that the intrinsic activity of the sugar transporters was modified via the P13K pathway. In conclusion, maternal GLP-2 and DEX reduced intestinal sugar uptake in their offspring. This may have nutritional implications for the offspring of mothers treated with GLP-2 or steroids. PMID:18993047

Drozdowski, Laurie A; Iordache, Claudiu; Clandinin, M Tom; Todd, Zoe; Gonnet, Maud; Wild, Gary; Uwiera, Richard R E; Thomson, Alan B R

2009-10-01

156

Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth Restriction  

Microsoft Academic Search

OBJECTIVE—We have examined maternal mechanisms for adult- onset glucose intolerance, increased adiposity, and atherosclerosis using two mouse models for intrauterine growth restriction (IUGR): maternal protein restriction and hypercholesterolemia. RESEARCH DESIGN AND METHODS—For these studies, we measured the amino acid levels in dams from two mouse models for IUGR: 1) feeding C57BL\\/6J dams a protein-restricted diet and 2) feeding C57BL\\/6J LDL

Kum Kum; S. Bhasin; Atila van Nas; Lisa J. Martin; Richard C. Davis; Sherin U. Devaskar; Aldons J. Lusis

2009-01-01

157

Maternal obesity enhances white adipose tissue differentiation and alters genome-scale DNA methylation in male rat offspring.  

PubMed

The risk of obesity (OB) in adulthood is strongly influenced by maternal body composition. Here we examined the hypothesis that maternal OB influences white adipose tissue (WAT) transcriptome and increases propensity for adipogenesis in the offspring, prior to the development of OB, using an established model of long-term metabolic programming. Employing an overfeeding-based rat model, in which exposure to OB is limited to preconception and gestation alone, we conducted global transcriptomic profiling in WAT, and gene/protein expression analysis of lipogenic and adipogenic pathways and examined adipogenic differentiation of WAT stromal-vascular cells ex vivo. Using reduced representation bisulfite sequencing we also evaluated genome-scale changes in DNA methylation in offspring WAT. Maternal OB led to extensive changes in expression of genes (± 1.8-fold, P ? .05), revealing a distinct up-regulation of lipogenic pathways in WAT. mRNA expression of a battery of sterol regulatory element-binding protein-1-regulated genes was increased in OB-dam offspring, which were confirmed by immunoblotting. In conjunction with lipogenic gene expression, OB-dam offspring showed increased glucose transporter-4 mRNA/protein expression and greater AKT phosphorylation following acute insulin challenge, suggesting sensitization of insulin signaling in WAT. Offspring of OB dams also exhibited increased in vivo expression of adipogenic regulators (peroxisome proliferator-activated receptor-?, CCAAT enhancer binding protein ? [C/EBP-?] and C/EBP-?), associated with greater ex vivo differentiation of WAT stromal-vascular cells. These transcriptomic changes were associated with alterations in DNA methylation of CpG sites and CGI shores, proximal to developmentally important genes, including key pro-adipogenic factors (Zfp423 and C/EBP-?). Our findings strongly suggest that the maternal OB in utero alters adipocyte commitment and differentiation via epigenetic mechanisms. PMID:23959936

Borengasser, Sarah J; Zhong, Ying; Kang, Ping; Lindsey, Forrest; Ronis, Martin J J; Badger, Thomas M; Gomez-Acevedo, Horacio; Shankar, Kartik

2013-11-01

158

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

PubMed

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

2014-08-01

159

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

SciTech Connect

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

Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. (Katholieke Universiteit Leuven (Belgium) Institut National de la Sante et de la Recherche Medical (France))

1988-04-01

160

Acupuncture stimulation at HT7 alleviates depression-induced behavioral changes via regulation of the serotonin system in the prefrontal cortex of maternally-separated rat pups.  

PubMed

A possible application of acupuncture in alleviating depression-like behavioral changes and regulating serotonin signaling in the prefrontal cortex (PFC) of maternally-separated rat pups was investigated in this study. On postnatal day 15, rat pups were maternally-separated and received acupuncture stimulation at acupoint HT7 or ST36 once a day for 7 days. On postnatal day 21, the tail suspension test was performed and the PFC was harvested. Tissue levels of serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were then measured by high-performance liquid chromatography and expression of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) were assessed by western blotting. Levels of 5-HT and 5-HIAA were not significantly changed, but the 5-HIAA/5-HT ratio was significantly increased by maternal separation. The immobility time of maternally-separated rat pups was increased, and increased 5-HTT expression and reduced BDNF level were observed in the PFC. But acupuncture stimulation at HT7 alleviated the behavioral change and regulated the changes of 5-HIAA/5-HT ratio, 5-HTT, and BDNF. In conclusion, acupuncture stimulation at HT7 can relieve maternal separation-induced changes, and we propose that regulation of the 5-HIAA/5-HT ratio and of 5-HTT expression by acupuncture stimulation are important acupuncture-induced benefits in this animal model of depression. PMID:22627707

Park, Hyemee; Yoo, Doyoung; Kwon, Sunoh; Yoo, Tae-Won; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

2012-07-01

161

Enhanced Maternal Aggression and Associated Changes in Neuropeptide Gene Expression in Multiparous Rats  

PubMed Central

While it has often been speculated that prior reproductive experience improves subsequent maternal care, few studies have examined specific changes in behavior during a first versus second lactation. During lactation mothers display heightened aggression toward male intruders, purportedly to protect vulnerable young. In the current study, maternal aggression was examined in primiparous and age-matched, multiparous females on postpartum days 5 (PPD5) and PPD15. Expression of oxytocin (OXT), oxytocin receptor (OXT-R), arginine vasopressin (AVP), arginine vasopressin V1a receptors (V1a), and corticotrophin releasing hormone (CRH) mRNA was measured following aggression testing at both time points using real-time quantitative PCR (qPCR) in brain regions previously implicated in the regulation of maternal aggression. Multiparity significantly enhanced maternal aggression on PPD5 but not on PPD15. In addition, this increased aggression was associated with region and gene specific changes in mRNA expression. These findings indicate that reproductive experience enhances maternal aggression, an effect that may be mediated by region specific alterations in neuropeptidergic activity. The adaptations observed in multiparous females provide an innate model for the study of neuroplasticity in the regulation of aggression. PMID:19824761

Nephew, Benjamin C.; Bridges, Robert S.; Lovelock, Dennis F.; Byrnes, Elizabeth M.

2009-01-01

162

Enhanced maternal aggression and associated changes in neuropeptide gene expression in multiparous rats.  

PubMed

Although it has often been speculated that prior reproductive experience improves subsequent maternal care, few studies have examined specific changes in behavior during a 1st versus 2nd lactation. During lactation, mothers display heightened aggression toward male intruders, purportedly to protect vulnerable young. In the current study, maternal aggression was examined in primiparous and age-matched multiparous females on postpartum days 5 (PPD5) and PPD15. Expression of oxytocin, oxytocin receptor, arginine vasopressin, arginine vasopressin V1a receptors, and corticotrophin-releasing hormone mRNA was measured following aggression testing at both time points using real-time quantitative PCR in brain regions previously implicated in the regulation of maternal aggression. Multiparity significantly enhanced maternal aggression on PPD5 but not on PPD15. In addition, this increased aggression was associated with region- and gene-specific changes in mRNA expression. These findings indicate that reproductive experience enhances maternal aggression, an effect that may be mediated by region-specific alterations in neuropeptidergic activity. The adaptations observed in multiparous females provide an innate model for the study of neuroplasticity in the regulation of aggression. PMID:19824761

Nephew, Benjamin C; Bridges, Robert S; Lovelock, Dennis F; Byrnes, Elizabeth M

2009-10-01

163

High-fat feeding of different fats during pregnancy and lactation in rats: Effects on maternal metabolism, pregnancy outcome, milk and tissue fatty acid profiles  

Microsoft Academic Search

This study was designed to examine the effects of consumption of different fats during pregnancy and lactation on maternal metabolism, pregnancy outcome, and milk and tissue fatty acid (FA) profiles. Wistar rats were divided into three groups according to dietary fat source: PM (40% crude palm oil), n = 7; SB (40% soybean oil), n = 7; and VS (40%

Anne Buison; Huiqing Lu; Feng Guo; K. L. Catherine Jen

1997-01-01

164

Effects of brief and long maternal separations on the HPA axis activity and the performance of rats on context and tone fear conditioning  

Microsoft Academic Search

Previous studies show that early life events result in neurobehavioural alterations that may be either beneficial or detrimental to the stress response. Given the close relationship between corticosterone secretion and mnemonic processes, the purpose of the present study was to investigate the effects of brief (BMS, 15min) and long maternal separations (LMS, 180min) on memory tasks in adult rats, assessed

Jussara Z. Guijarro; Paula A. Tiba; Tatiana L. Ferreira; Suzi E. Kawakami; Maria Gabriela M. Oliveira; Deborah Suchecki

2007-01-01

165

EFFECTS OF MATERNAL DIETARY RESTRICTION DURING GESTATION AND LACTATION, MUSCLE, SEX AND AGE ON VARIOUS INDICES OF SKELETAL MUSCLE GROWTH IN THE RAT 1  

Microsoft Academic Search

Summary Induced impairment of growth rate and mature size in the rat was used to characterize and compare histological and biochemical indices of skeletal muscle hyperplastic and hypertrophic growth. Maternal nutritional restriction during gestation and lactation caused a 54% reduction in progeny body weight before realimentation was begun at weaning. A compen- satory growth response was observed in restrict- ed

D. H. Beermann

166

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

PubMed

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

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

1998-02-01

167

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

PubMed

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

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

2014-01-01

168

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

PubMed Central

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

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

2013-01-01

169

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

EPA Science Inventory

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

170

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

EPA Science Inventory

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

171

Reciprocal Changes in Maternal and Fetal Metabolism of Corticosterone in Rat During Gestation  

E-print Network

concentration of glucocorticoids is ascribed to the placenta. It protects the fetuses against maternal cortisol to blockers that inhibit the activity of this enzyme reduces offspring birth weight and pro- duces long+ -dependent enzyme (11HSD2), which operates only as an oxidase and catalyzes the conversion of cortisol

Miksik, Ivan

172

Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

173

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

PubMed Central

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

2014-01-01

174

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

PubMed

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

2014-01-01

175

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. PMID:20207831

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

2010-01-01

176

Maternal Hypoxia Increases the Activity of MMPs and Decreases the Expression of TIMPs in the Brain of Neonatal Rats  

PubMed Central

A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. PMID:20017119

Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P.; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H.; Tang, Jiping

2010-01-01

177

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. PMID:21872599

Kojima, Sayuri; Alberts, Jeffrey R.

2011-01-01

178

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

PubMed

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism. PMID:24972880

Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

2015-02-01

179

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. PMID:25031406

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

2014-01-01

180

Hypoactivation of CRF receptors, predominantly type 2, in the medial-posterior BNST is vital for adequate maternal behavior in lactating rats.  

PubMed

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

2014-07-16

181

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

PubMed

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

Martisova, Eva; Aisa, Bárbara; Guereñu, Gorka; Ramírez, María Javier

2013-05-01

182

The effects of maternal ethanol exposure on neurotransmission and second messenger systems: a quantitative autoradiographic study in the rat brain.  

PubMed

The effects of maternal ethanol exposure on neurotransmission and second messenger systems were examined in rats using histochemistry and in vitro autoradiography. Thirty % ethanol was administered to pregnant rats from gestational day 7 to the day of delivery. Quantitative autoradiography was used to map muscarinic cholinergic, dopamine D2, adenosine A1, and inositol 1,4,5-trisphosphate binding sites, as well as to localize adenylate cyclase and protein kinase C. We found no difference in the patterns of staining with acetylcholinesterase and Timm's stain between control and prenatally ethanol-exposed rats on postnatal day (PN) 30. In the ethanol-exposed rats, [3H]forskolin binding sites were increased during early development in the CA1 subfield of the hippocampus and the occipital cortex; [3H]phorbol ester binding sites were increased in the cortex, striatum, and hippocampus; hippocampal muscarinic cholinergic sites were increased on PN4 and 30; adenosine A1 binding was reduced on PN10 in most regions examined, but was increased in the CA1 subfield on PN30; dopamine D2 receptor levels were significantly reduced on PN30 in the striatum; and IP3 receptors were decreased in most regions studied, but particularly in the cerebellum. Thus, some of these changes were transient and others were long-lasting. Although histopathological abnormalities were minimal, the alterations of binding sites in the cerebellum (the coordination center) and in the hippocampus (related to memory and learning) that were detected may contribute to the behavioral and mental deterioration seen in the fetal alcohol syndrome. PMID:1662122

Nio, E; Kogure, K; Yae, T; Onodera, H

1991-09-19

183

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

EPA Science Inventory

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

184

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

EPA Science Inventory

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

185

Hypothalamic galanin levels in weanling rats exposed to maternal low-protein diet  

Microsoft Academic Search

Perinatal malnutrition and growth retardation at birth are risk factors for the later development of Syndrome X which is characterized by overweight and hyperlipidaemia, associated with hyperinsulinaemia, impaired glucose tolerance and hypertension. The offspring of mother rats exposed to protein malnutrition during gestation and lactation (LP) develop syndrome X-like disturbances during life, for unclear reasons. In male rats born to

Andreas Plagemann; Fanny Rittel; Thomas Harder; Thomas Waas; Thomas Ziska; Wolfgang Rohde

2000-01-01

186

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. PMID:23071537

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

2012-01-01

187

Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat.  

PubMed

Earlier studies at our laboratory indicated that several hydroxylated polychlorinated biphenyls (OH-PCBs) detected in human blood could specifically inhibit thyroxine (T(4)) transport by competitive binding to the thyroid hormone transport protein transthyretin (TTR) in vitro. In the present study we investigated the effects of prenatal exposure to 5 mg/kg body weight of [14C]-labeled or unlabeled 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107), one of the major metabolites of PCBs detected in human blood, from gestation days (GD) 10 to 16 on thyroid hormone status and metabolism in pregnant rats and their fetuses at GD 17 and GD 20. 4-OH-CB107 is a metabolite of both 2,3,3',4,4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118). We were able to show the accumulation of 4-OH-CB107 in the fetal compartment. The fetal/maternal ratios at GD 20 in liver, cerebellum, and plasma were 11.0, 2.6, and 1.2, respectively. The 14C-4-OH-CB107-derived radioactivity in plasma was bound to TTR in both dams and fetuses. Fetal plasma TT(4) and FT(4) levels were significantly decreased at GD 17 and GD 20 (89% and 41% respectively at GD 20). Fetal thyroid stimulating hormone levels were increased by 124% at GD 20. The T(4) concentrations in fetal forebrain homogenates at GD20 were reduced by 35%, but no effects could be detected on brain T(3) concentrations. The deiodination of T(4) to T(3) was significantly increased in fetal forebrain homogenates at GD 17, and unaltered at GD 20. In addition, no alterations were observed in maternal and fetal hepatic T(4)-UDP-glucuronosyltransferase activity, type I deiodinase activity, and EROD activity. In conclusion, exposure of pregnant rats to 4-OH-CB107 results in the distribution of the compound in the maternal and fetal compartment, which is probably caused by the binding of the PCB metabolite to TTR. Consequently, TT(4) levels in fetal plasma and brain samples were reduced. Despite reductions in fetal brain T(4) levels, the active hormone (T(3)) in fetal brains remained unaffected. PMID:12151632

Meerts, Ilonka A T M; Assink, Yvonne; Cenijn, Peter H; Van Den Berg, Johannes H J; Weijers, Bert M; Bergman, Ake; Koeman, Jan H; Brouwer, Abraham

2002-08-01

188

Prenatal exposure of a novel antipsychotic aripiprazole: impact on maternal, fetal and postnatal body weight modulation in rats.  

PubMed

Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring. PMID:24138551

Singh, K P; Tripathi, Nidhi

2014-03-01

189

The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.  

PubMed

Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood. PMID:24905448

Nascimento, Luciana; Freitas, Cristiane M; Silva-Filho, Reginaldo; Leite, Ana Catarina R; Silva, Alessandra B; da Silva, Aline Isabel; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; Maia, Maria Bernadete Souza; Fernandes, Mariana P; Lagranha, Claudia

2014-08-01

190

EFFECTS ON THE FETUS OF MATERNAL BENOMYL EXPOSURE IN THE PROTEIN-DEPRIVED RAT  

EPA Science Inventory

The separate and combined effects of protein deprivation and benomyl ((methyl 1-butylcarbomoyl)2-benzimidazole carbamate) exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups...

191

Changes in Intestinal Glucocorticoid Sensitivity in Early Life Shape the Risk of Epithelial Barrier Defect in Maternal-Deprived Rats  

PubMed Central

Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. Rat gut is immature at birth, and high intestinal GC sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of maternal separation (MS)-associated GC release in preterm babies, and whether GC sensitivity may shape MS effects in immature gut. A 4 hours-MS applied once at postnatal day (PND)10 enhanced plasma corticosterone in male and female pups, increased by two times the total in vivo intestinal permeability (IP) to oral FITC-Dextran 4 kDa (FD4) immediately after the end of MS, and induced bacterial translocation (BT) to liver and spleen. Ussing chamber experiments demonstrated a 2-fold increase of permeability to FD4 in the colon immediately after the end of MS, but not in the ileum. Colonic permeability was not only increased for FD4 but also to intact horseradish peroxidase 44 kDa in MS pups. In vivo, the glucocorticoid receptor (GR) antagonist RU486 or ML7 blockade of myosin light chain kinase controlling epithelial cytoskeleton contraction prevented MS-induced IP increase to oral FD4 and BT. In addition, the GR agonist dexamethasone dose-dependently mimicked MS-increase of IP to oral FD4. In contrast, MS effects on IP to oral FD4 and BT were absent at PND20, a model for full-term infant, characterized by a marked drop of IP to FD4 in response to dexamethasone, and decreased GR expression in the colon only compared to PND10 pups. These results show that high intestinal GC responsiveness in a rat model of prematurity defines a vulnerable window for a post-delivery MS, evoking immediate disruption of epithelial integrity in the large intestine, and increasing susceptibility to macromolecule passage and bacteremia. PMID:24586321

Moussaoui, Nabila; Braniste, Viorica; Ait-Belgnaoui, Afifa; Gabanou, Mélissa; Sekkal, Soraya; Olier, Maiwenn; Théodorou, Vassilia; Martin, Pascal G. P.; Houdeau, Eric

2014-01-01

192

Developmental Timing of the Effects of Maternal Care on Gene Expression and Epigenetic Regulation of Hormone Receptor Levels in Female Rats  

PubMed Central

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

2013-01-01

193

Role of pups' ultrasonic calls in a particular maternal behavior in Wistar rat: pups' anogenital licking.  

PubMed

Stimuli from pups maintain maternal behavior in the postpartum period. Olfactory cues are strongly involved in a particular component of maternal behavior: anogenital licking (MAGL). In addition to the olfactive stimulus, ultrasonic calls from pups are critical in ensuring pup survival. Pups emit vocalizations in distress situations. In a first experiment, pups' calls are recorded around MAGL sequences. In 2 out of 3 cases these calls appear to induce MAGL behavior from the dam with preputialectomised pups as well as with intact pups, but preputialectomised pups alone call again at the end of MAGL sequences. In a second experiment, ultrasonic calls from pups emitted just before AGL sequences were recorded and played back to dams in a glass-dish selection test. Whatever the pups' treatment (preputialectomised or sham), dams showed the specific ingestive behavior towards filter paper impregnated with dodecyl propionate (DP) when auditory cues (pups' ultrasonic calls) and olfactory cues (DP) were combined. The coordination of pups' ultrasonic calls and anogenital odor in MAGL behavior is discussed, ultrasonic calls might be an inducing factor and DP the regulating factor. PMID:1449642

Brouette-Lahlou, I; Vernet-Maury, E; Vigouroux, M

1992-09-28

194

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

PubMed

The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD) as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk) HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERB?, CRY, PER) and metabolic (PPAR?, SIRT1) genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPAR? mRNA expression: i) decreased mRNA synthesis rates; and ii) increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPAR? transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPAR? transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPAR? expression prior to obesity development. PMID:24416203

Borengasser, Sarah J; Kang, Ping; Faske, Jennifer; Gomez-Acevedo, Horacio; Blackburn, Michael L; Badger, Thomas M; Shankar, Kartik

2014-01-01

195

Perinatal Maternal Food Restriction Induces Alterations in Hypothalamo-Pituitary-Adrenal Axis Activity and in Plasma Corticosterone-Binding Globulin Capacity of Weaning Rat Pups  

Microsoft Academic Search

We investigated the effects of perinatal maternal malnutrition on the hypothalamo-pituitary-adrenal (HPA) axis activity in both basal and stressful conditions in newborn rats at weaning. Mothers from the control group were fed ad libitum. Mothers exposed to food restriction received 50% (FR50) of the daily intake of pregnant dams during the last week of gestation (Pre group), lactation (Post group)

Marion Léonhardt; Jean Lesage; Laurence Dufourny; Anne Dickès-Coopman; Valérie Montel; Jean-Paul Dupouy

2002-01-01

196

High Fat Diet and In Utero Exposure to Maternal Obesity Disrupts Circadian Rhythm and Leads to Metabolic Programming of Liver in Rat Offspring  

PubMed Central

The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD) as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk) HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERB?, CRY, PER) and metabolic (PPAR?, SIRT1) genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPAR? mRNA expression: i) decreased mRNA synthesis rates; and ii) increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPAR? transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPAR? transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPAR? expression prior to obesity development. PMID:24416203

Borengasser, Sarah J.; Kang, Ping; Faske, Jennifer; Gomez-Acevedo, Horacio; Blackburn, Michael L.; Badger, Thomas M.; Shankar, Kartik

2014-01-01

197

The effect of reduced maternal protein intake during pregnancy on placental lipid composition in the rat: effect of glycine supplementation of the low protein diet  

Microsoft Academic Search

The objective of this study was to determine whether consumption of a maternal low-protein (MLP) diet during pregnancy alters placental lipid composition, and whether this was prevented by supplementation of the MLP diet with glycine, that ameliorates some effects of this diet. Rats (n = 5\\/group) were fed diets containing 18%(w\\/w) casein (Control), 9%(w\\/w) casein (MLP), or MLP plus 3%(w\\/w)

Graham C. Burdge; Rebecca L. Dunn; Alan A. Jackson

2004-01-01

198

IFITM proteins restrict antibody-dependent enhancement of dengue virus infection.  

PubMed

Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections. PMID:22479637

Chan, Ying Kai; Huang, I-Chueh; Farzan, Michael

2012-01-01

199

Oxytocin receptors in the nucleus accumbens shell are involved in the consolidation of maternal memory in postpartum rats  

E-print Network

October 2010 Keywords: Maternal behavior Social behavior Oxytocin antagonist Hippocampus Caudate nucleusOxytocin receptors in the nucleus accumbens shell are involved in the consolidation of maternal for maternal behavior after a 10-day pup isolation period. Females receiving a high dose of the antagonist

Sokolowski, Marla

200

IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection  

Microsoft Academic Search

Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins

Ying Kai Chan; I-Chueh Huang; Michael Farzan

2012-01-01

201

Chronic low level maternal carbon monoxide exposure and fetal growth and development. [Rats  

Microsoft Academic Search

We investigated the effects on fetal growth and development of continuous exposure of pregnant rats to low level carbon monoxide (30 or 90 ppM CO) and a low oxygen atmosphere (13% Oâ). While neither CO concentration induced a hematologic response in the pregnant animals, 13% Oâ exposure elicited an increase in hematocrit, the number of erythrocytes and hemoglobin concentration. Fetal

D. J. Garvey; L. D. Longo

1978-01-01

202

ASSESSMENT OF MATERNAL TOXICITY, EMBRYOTOXICITY AND TERATOGENIC POTENTIAL OF SODIUM CHLORITE IN SPRAGUE-DAWLEY RATS  

EPA Science Inventory

Groups of up to 13 pregnant rats were individually caged. Body weight, food and water consumption were recorded at days 1, 8, 15 and 22 of gestation and the dams were treated on days 8-15 with sodium chlorite, 0.1%, 0.5% or 2% in drinking water or by injection of 10, 20, or 50 mg...

203

Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats  

Microsoft Academic Search

Summary Exposure to early stressful adverse life events may increase vulnerability to psychopathol- ogy in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Male Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life

Bárbara Aisa; Rosa Tordera; Berta Lasheras; Joaquín Del Río; Maria J. Ramírez

2007-01-01

204

Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.  

PubMed

Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks. PMID:23906636

Haghani, M; Shabani, M; Moazzami, K

2013-10-10

205

EFFECTS ON THE FETUS OF MATERNAL NITROFEN EXPOSURE IN THE PROTEIN-DEPRIVED RAT  

EPA Science Inventory

The separate and combined effects of protein deprivation and nitrofen exposure were studied in the pregnant rat. Animals were fed diets containing 24, 8, 6 or 4% casein throughout gestation. Within each diet group, sub-groups were gavage-fed with 12.5 (lower dose) and 25 (higher ...

206

Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat  

Microsoft Academic Search

Epidemiological evidence suggests that hypertension and coronary heart disease are programmed by exposure to a poor diet during intrauterine life. It has been proposed that the prenatal environment may exert an adverse effect on the development of the kidney and hence later control of blood pressure. These assertions are supported by animal experiments. In the rat, fetal exposure to a

Simon C Langley-Evans; Simon JM Welham; Alan A Jackson

1999-01-01

207

Nephron number and blood pressure in rat offspring with maternal high-protein diet  

Microsoft Academic Search

This study investigated the effects of a high-protein diet during pregnancy on nephron endowment and subsequent levels of blood pressure in the offspring. Female WKY rats were fed either a normal (20%, NPD) or a high (54%, HPD) protein diet during pregnancy. Male offspring were paired at birth. At 4 weeks of age, 1 of the pair was randomly chosen

Monika A. Zimanyi; John F. Bertram; Jane M. Black

2002-01-01

208

Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes.  

PubMed

Diet-mediated changes in transcriptional programs that promote the early differentiation of the mammary gland may lead to reduced breast cancer risk. The disparity in adult breast cancer incidence between Asian women and Western counterparts is attributed partly to high soy food intake. Here, we conducted genome-wide profiling of mammary tissues of weanling rats exposed to soy protein isolate (SPI) or control casein (CAS) via maternal diet to evaluate the contribution of early exposure on mammary gene expression. Of the identified 18 up- and 39 downregulated genes with SPI relative to CAS, a subset was associated with lipid metabolic pathways, consistent with reduced mammary adipocyte size and suggesting stromal adipocyte-specific genomic changes. Female offspring of rats fed SPI tended to have fewer terminal end buds (P = 0.06) and had significantly lower body weight and abdominal fat mass. To demonstrate the functional consequence of SPI-mediated adipocyte metabolic changes on neighboring mammary epithelium, the expression of in vivo regulated genes in 3T3-L1 adipocytes treated with soy isoflavone genistein and effects of the resultant conditioned medium (CM) on the differentiation of HC11 mammary epithelial cells were evaluated by quantitative RT-PCR and/or Western immunoblots. In differentiated 3T3-L1, genistein decreased fatty acid synthase and stearoyl-CoA desaturase and increased hydroxysteroid 11-beta dehydrogenase 1 expression. CM from genistein-treated adipocytes had higher adiponectin levels and augmented prolactin-induced, glucocorticoid-regulated beta-casein levels. These findings suggest that soy-associated components, by targeting mammary adipocytes, alter paracrine signaling to enhance mammary epithelial differentiation, with important implications for the prevention of breast cancer associated with obesity and obesity-related diseases. PMID:19321580

Su, Ying; Shankar, Kartik; Simmen, Rosalia C M

2009-05-01

209

Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats  

Microsoft Academic Search

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for re- peated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CDt) rats were administered MEL or vehicle by gavage on gestation days (gd) 6 -19. MEL-treated groups received 1-,

G. Jahnke; M. Marr; C. Myers; R. Wilson; G. Travlos; C. Price

1999-01-01

210

Effect of maternal fluoride exposure on developing CNS of rats: protective role of Aloe vera, Curcuma longa and Ocimum sanctum.  

PubMed

Fluoride is toxic to neuronal development and its excessive intake during pregnancy cause adverse effects on neonatal development. The present study examined the presence of oxidative stress during maternal exposure of fluoride and the therapeutic strategy of Aloe vera, Curcuma longa and Ocimum sanctum extracts in functional prevention of fluoride led oxidative stress. The pregnant Wistar rats were exposed to 100 ppm fluoride in drinking water and pups born to them were supplemented with phytoextracts daily. On 21st postpartum day, the pups were sacrificed to analyse fluoride and oxidative stress markers. Fluoride exposure significantly increased its accumulation, lipid peroxidation and decreased the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione levels in discrete regions of the central nervous system (CNS) of pups indicating oxidative stress and inhibited antioxidant defense. The results implied the vulnerability of developing CNS to fluoride toxicity. On phytoextract supplementation, the oxidant devastation was suppressed by regaining antioxidant homeostasis near normal level proving efficacy and therapeutic strategy. Among the phytoextracts supplemented the Ocimum sanctum is found to be more effective. PMID:21341542

Madhusudhan, N; Basha, P Mahaboob; Rai, Puja; Ahmed, Fiyaz; Prasad, G Ravi

2010-08-01

211

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: mikit@med.kagawa-u.ac.jp [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)

2013-12-06

212

The effect of maternal administration of captopril on fetal development in rat.  

PubMed

Captopril an angiotensin converting enzyme (ACE) inhibitor, was evaluated for teratogenic potential in Wistar rats. The drug was administered daily from 6 to 15 day of gestation by gavage (0, 3, 10 and 30 mg/kg/day) and perinatal studies were conducted. Captopril decreased food consumption and suppressed gain in body weight. However, no alteration in food efficiency index was observed. The treatment of rats with captopril in doses of 10 and 30 mg/kg, significantly reduced the mean number of implants per litter size and produced intrauterine growth retardation. The incidence of external and visceral malformations were neither dose related nor significantly different from those of controls. In addition, animal treated with these dose levels showed decreased ossification of digits, sternum and skull of the offsprings. The data of the present study indicates that captopril was not found to be teratogenic to Wistar rats. However, adverse effects on intrauterine growth, fetal ossification, neonatal growth and survival rate were seen among the pups. PMID:1784836

al-Shabanah, O A; al-Harbi, M M; alGharably, N M; Islam, M W

1991-08-01

213

Short- and long-term effects of a maternal low-protein diet on ventilation, O?/CO? chemoreception and arterial blood pressure in male rat offspring.  

PubMed

Maternal undernutrition increases the risk of adult arterial hypertension. The present study investigated the short- and long-term effects of a maternal low-protein diet on respiratory rhythm, O?/CO? chemosensitivity and arterial blood pressure (ABP) of the offspring. Male Wistar rats were divided into two groups according to their mothers' diets during gestation and lactation: control (NP, 17% of casein) and low-protein (LP, 8% of casein) groups. Direct measurements of ABP, respiratory frequency (RF), tidal volume (V T) and ventilation (VE), as well as hypercapnia (7% CO?) and hypoxia (7% O?) evoked respiratory responses were recorded from the awake male offspring at the 30th and 90th days of life. Blood samples were collected for the analyses of protein, creatinine and urea concentrations. The LP offspring had impaired body weight and length throughout the experiment. At 30 d of age, the LP rats showed a reduction in the concentrations of total serum protein (approximately 24%). ABP in the LP rats was similar to that in the NP rats at 30 d of age, but it was 20% higher at 90 d of age. With respect to ventilatory parameters, the LP rats showed enhanced RF (approximately 34%) and VE (approximately 34%) at 30 d of age, which was associated with increased ventilatory responses to hypercapnia (approximately 21% in VE) and hypoxia (approximately 82% in VE). At 90 d of age, the VE values and CO?/O? chemosensitivity of the LP rats were restored to the control range, but the RF values remained elevated. The present data show that a perinatal LP diet alters respiratory rhythm and O?/CO? chemosensitivity at early ages, which may be a predisposing factor for increased ABP at adulthood. PMID:24059468

de Brito Alves, José Luiz; Nogueira, Viviane Oliveira; de Oliveira, Gerliny Bezerra; da Silva, Glauber Santos Ferreira; Wanderley, Almir Gonçalves; Leandro, Carol Góis; Costa-Silva, João Henrique

2014-02-01

214

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. PMID:24886632

2014-01-01

215

Effects of maternally exposed colouring food additives on cognitive performance in rats.  

PubMed

Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. Effects on spatial learning and memory were evaluated by Morris water maze, behavioural effects were evaluated by open-field test and forced swim test. Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity. PMID:22323474

Doguc, Duygu Kumbul; Ceyhan, Betul Mermi; Ozturk, Mustafa; Gultekin, Fatih

2013-08-01

216

Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung.  

PubMed

To investigate mechanisms of chemical-induced congenital heart defects (CHD) we have developed a rat model using dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant, trimethadione (TMD). Dosing pregnant rats with 300mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses) produces a mean 74% incidence of CHD with inter litter variability ranging from 40 to 100%. The goal of this study was to determine if the variability in maternal serum concentrations of DMO on GD 14, a surrogate marker for total exposure, was related to the inter-litter differences in teratogenic outcomes. To test this hypothesis, pregnant rats were dosed as described above and serum levels of DMO assessed on GD 14. On GD 21, foetuses were collected by caesarean section, assessed for a number endpoints and the outcomes were correlated with the GD 14 serum concentrations of DMO. DMO exposure was associated with decreased foetal body weight, increased incidence of sternal defects and CHD, but these endpoints were not meaningfully correlated with maternal concentrations of DMO. Novel findings were decreased viability as measured one-hour following caesarean section, and delayed alveolar maturation. The major conclusions from these studies were first, that serum DMO concentrations on GD 14 did not predict teratogenicity, and second, delayed lung development may contribute to the decreased survival of foetuses at the time of caesarean section. PMID:25446330

Rodger, Ian; Lam, Isabel; Purssell, Elizabeth; Thompson, Mesha; Rutter, Allison; Ozolinš, Terence Rs

2014-12-01

217

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. PMID:24505458

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

2014-01-01

218

A Maternal High Fat Diet Has Long-Lasting Effects on Skeletal Muscle Lipid and PLIN Protein Content in Rat Offspring at Young Adulthood.  

PubMed

A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI-58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19d) and young adulthood (3mo). Female rats (28d old, n = 9/group) were fed control (CON, AIN93G, 7 % soybean oil) or HFD (AIN93G, 20 % lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19d) and 3mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI-58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood. PMID:25552350

MacPherson, Rebecca E K; Castelli, Laura M; Miotto, Paula M; Frendo-Cumbo, Scott; Milburn, Amanda; Roy, Brian D; LeBlanc, Paul J; Ward, Wendy E; Peters, Sandra J

2015-02-01

219

Behavioral alterations in rat offspring following maternal immune activation and ELR-CXC chemokine receptor antagonism during pregnancy: implications for neurodevelopmental psychiatric disorders.  

PubMed

Research suggests that maternal immune activation (MIA) during pregnancy increases the risk of neurodevelopmental disorders including schizophrenia and autism in the offspring. Current theories suggest that inflammatory mediators including cytokines and chemokines may underlie the increased risk of these disorders in humans. For example, elevated maternal interleukin-8 (IL-8) during pregnancy is associated with increased risk of schizophrenia in the offspring. Given this association, the present experiments examined ELR-CXC chemokines CXCL1 and CXCL2, rodent homologues of human IL-8, and activation of their receptors (CXCR1 and CXCR2) in an established rodent model of MIA. Pregnant Long Evans rats were treated with the viral mimetic polyinosinic-polycytidylic acid (polyI:C; 4 mg/kg, i.v.) on gestational day 15. Protein analysis using multiplex assays and ELISA showed that polyI:C significantly increased maternal serum concentrations of interleukin-1?, tumor necrosis factor, and CXCL1 3h after administration. Subsequent experiments tested the role of elevated maternal CXCL1 on behavior of the offspring by administering a CXCR1/CXCR2 antagonist (G31P; 500 ?g/kg, i.p.; 1h before, 48 and 96 h after polyI:C treatment). The male offspring of dams treated with polyI:C demonstrated subtle impairments in prepulse inhibition (PPI), impaired associative and crossmodal recognition memory, and altered behavioral flexibility in an operant test battery. While G31P did not completely reverse the behavioral impairments caused by polyI:C, it enhanced PPI during adolescence and strategy set-shifting and reversal learning during young adulthood. These results suggest that while polyI:C treatment significantly increases maternal CXCL1, elevations of this chemokine are not solely responsible for the effects of polyI:C on the behavior of the offspring. PMID:25445065

Ballendine, Stephanie A; Greba, Quentin; Dawicki, Wojciech; Zhang, Xiaobei; Gordon, John R; Howland, John G

2015-03-01

220

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

PubMed Central

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

2014-01-01

221

Role of maternal tissue in the synthesis of polyunsaturated fatty acids in response to a lipid-deficient diet during pregnancy and lactation in rats.  

PubMed

During pregnancy and lactation, metabolic adaptations involve changes in expression of desaturases and elongases (Elovl2 and Elovl5) in the mammary gland and liver for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (AA) required for fetal and postnatal growth. Adipose tissue is a pool of LC-PUFAs. The response of adipose tissue for the synthesis of these fatty acids in a lipid-deficient diet of dams is unknown. The aim of this study was to explore the role of maternal tissue in the synthesis of LC-PUFAs in rats fed a low-lipid diet during pregnancy and lactation. Fatty acid composition (indicative of enzymatic activity) and gene expression of encoding enzymes for fatty acid synthesis were measured in liver, mammary gland and adipose tissue in rats fed a low-lipid diet. Gene expression of desaturases, elongases, fatty acid synthase (Fasn) and their regulator Srebf-1c was increased in the mammary gland, liver and adipose tissue of rats fed a low-lipid diet compared with rats from the adequate-lipid diet group throughout pregnancy and lactation. Genes with the highest (P<0.05) expression in the mammary gland, liver and adipose tissue were Elovl5 (1333%), Fads2 (490%) and Fasn (6608%), respectively, in a low-lipid diet than in adequate-lipid diet. The percentage of AA in the mammary gland was similar between the low-lipid diet and adequate-lipid diet groups during the second stage of pregnancy and during lactation. The percentage of monounsaturated and saturated fatty acids was significantly (P<0.05) increased throughout pregnancy and lactation in all tissues in rats fed a low-lipid diet than in rats fed an adequate-lipid diet. Results suggest that maternal metabolic adaptations used to compensate for lipid-deficient diet during pregnancy and lactation include increased expression of genes involved in LC-PUFAs synthesis in a stage- and tissue-specific manner and elevated lipogenic activity (saturated and monounsaturated fatty acid synthesis) of maternal tissues including adipose tissue. PMID:25046614

González, Raúl Sánchez; Rodriguez-Cruz, Maricela; Maldonado, Jorge; Saavedra, Filiberto Jasso

2014-10-01

222

Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.  

PubMed Central

To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be clinically euthyroid if their T3 levels are normal. Images PMID:2394838

Calvo, R; Obregón, M J; Ruiz de Oña, C; Escobar del Rey, F; Morreale de Escobar, G

1990-01-01

223

Inhibition and recovery of maternal and fetal cholinesterase enzyme activity following a single cutaneous dose of methyl parathion and diazinon, alone and in combination, in pregnant rats.  

PubMed

Pregnant Sprague-Dawley rats (14-18 days of gestation) were treated with a single cutaneous subclinical dose(s) of 10 mg kg(-1) (15% of LD(50)) of methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) and 65 mg kg(-1) (15% of LD(50)) of diazinon (O,O)-diethyl O-2-isopropyl-6-methylpyrimidinyl phosphorothioate, and their combination. Animals were sacrificed at 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Inhibition of maternal and fetal cholinesterase enzyme activity has been determined. Methyl parathion significantly inhibited maternal and fetal brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) activity within 24 h after dosing. Diazinon and a mixture of methyl parathion and diazinon caused lesser inhibition compared with methyl parathion alone. Recovery of maternal and fetal brain AChE activity was in the order of diazinon > combination of diazinon and methyl parathion > methyl parathion 96 h after dosing. Although fetal plasma BuChE activity recovered to 100% of control within 96 h of application, maternal BuChE activity remained inhibited to 55% and 32% of control 96 h after application of methyl parathion and a mixture of methyl parathion and diazinon, respectively. Following a single dermal dose of methyl parathion, the activity of maternal liver BuChE was 63% of control 2 h after dosing, whereas inhibition of placental AChE or BuChE activity occurred 12 and 1 h following a single dose of methyl parathion, corresponding to activities of 63% and 54% of control, respectively. Diazinon, alone or in combination with methyl parathion, did not inhibit significantly the maternal liver BuChE or placental AChE and BuChE activity. The results suggest that dermal application of a single dose of methyl parathion and diazinon, alone or in combination, has an easy access into maternal and fetal tissues, resulting in inhibition of cholinesterase enzymes. The lower inhibitory effect of the combination of methyl parathion and diazinon might be due to competition of diazinon with methyl parathion for cytochrome P-450 enzymes, resulting in formation of the potent cholinesterase inhibitor methyl paraoxon. The faster recovery of fetal cholinesterase enzymes is attributed to the rapid de novo synthesis of cholinesterase fetal tissues compared with the mother. PMID:11481665

Abu-Qare, A W; Abou-Donia, M B

2001-01-01

224

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

PubMed

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

2013-01-01

225

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in dahl salt-sensitive rats.  

PubMed

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

226

Oral leptin treatment in suckling rats ameliorates detrimental effects in hypothalamic structure and function caused by maternal caloric restriction during gestation.  

PubMed

A poor prenatal environment brings about perturbations in leptin surge and hypothalamic circuitry that program impaired ability to regulate energy homeostasis in adulthood. Here, using a rat model of moderate maternal caloric restriction during gestation, we aimed to investigate whether leptin supplementation with physiological doses throughout lactation is able to ameliorate the adverse developmental malprogramming effects exerted in offspring hypothalamus structure and function. Three groups of male and female rats were studied: the offspring of ad libitum fed dams (controls), the offspring of 20% calorie restricted dams during the first part of pregnancy (CR), and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Animals were sacrificed on postnatal day 25. Morphometric and immunohistochemical studies on arcuate (ARC) and paraventicular (PVN) nucleus were performed and hypothalamic expression levels of selected genes were determined. In CR males, leptin treatment restored, at least in part, the number of immunoreactive neuropeptide Y (NPY(+)) cells in ARC, the total number of cells in PVN, hypothalamic NPY, cocaine- and amphetamine-regulated transcript (CART) and suppressor of cytokine signalling-3 (SOCS-3) mRNA levels, and plasma leptin levels, which were decreased in CR animals. CR-Leptin males showed higher hypothalamic long-form leptin receptor (ObRb) mRNA levels, compared to control and CR animals. In CR females, leptin treatment reverted the increased number of cells in ARC and cell density in ARC and PVN, and reduced hypothalamic SOCS-3 mRNA expression to levels similar to controls. Leptin treatment also reverted the increased relative area of NPY(+) fibers in the PVN occurring in CR animals. In conclusion, leptin supplementation throughout lactation is able to revert, at least partly, most of the developmental effects on hypothalamic structure and function caused by moderate maternal caloric restriction during gestation, and hence making this metabolic malprogramming reversible to some extent. PMID:24312379

Konieczna, Jadwiga; García, Ana Paula; Sánchez, Juana; Palou, Mariona; Palou, Andreu; Picó, Catalina

2013-01-01

227

A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development.  

PubMed

Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats. BPA was orally administered at a daily dose of 5 ?g/kg body weight to F0 pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to F1 offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as "non-maternal" behaviors in F0 and F1 dams from parturition until LD 8. The flavor preferences of F1 and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21-34 and PND 86-99. BPA exposure: 1) decreased maternal behavior in F1 dams, 2) caused developmental defects in both F1 and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in F1, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change. Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure. PMID:24269606

Boudalia, Sofiane; Berges, Raymond; Chabanet, Claire; Folia, Mireille; Decocq, Laurence; Pasquis, Bruno; Abdennebi-Najar, Latifa; Canivenc-Lavier, Marie-Chantal

2014-01-01

228

Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation  

PubMed Central

Background Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH. Results CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. Conclusion The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS. PMID:23249427

2012-01-01

229

Effect of moderate dietary protein restriction on the progression of overt diabetic nephropathy: a 6-mo prospective study13  

Microsoft Academic Search

To assess whether moderate dietary protein re- striction can delay the progression of overt diabetic nephropathy, 22 subjects with insulin-dependent diabetes mellitus were ran- domly assigned to an unrestricted protein diet (> I.6 gkg body 1 . d? ') or a moderately protein-restricted diet (0.8 gkg body wt?' d') and followed prospectively for six mo. Direct isotope methods were used

Frederick J Raal; W John Kalk; Marie Lawson; Jan D Esser; Ria Buys; Louise Fourie; Vanessa R Panz

230

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

2007-01-01

231

Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression in Fetal Rat Brain  

E-print Network

Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression, Massachusetts 01655 Despite clinical evidence that thyroid hormone is essential for brain development before birth, effects of thyroid hormone on the fetal brain have been largely unexplored. One mechanism

Zoeller, R. Thomas

232

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

PubMed

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

2014-09-01

233

Effect of timing of iron supplementation on maternal and neonatal growth and iron status of iron-deficient pregnant rats.  

PubMed

We have previously shown that maternal iron (Fe) deficiency not only reduces fetal size, but also increases blood pressure in the offspring when they are adults. In this paper we examine whether there are critical periods when supplementation reverses or fails to reverse the effect both on size and on expression of genes of Fe metabolism. We made dams Fe deficient, mated them and provided supplements of Fe in the diet from the beginning of gestation (0.5 days), from 7.5 days or from 14.5 days. Within 12 h of birth, dams and neonates were killed and tissues taken and examined. Fe deficiency throughout pregnancy reduces neonatal size. Supplementation from the beginning of the first, second or third week all reduced the effect. Maternal haematocrit was restored to normal levels only in animals given supplements for at least 2 weeks. In contrast, the neonates' Fe levels were normal in all supplemented groups. These results were mirrored in liver Fe levels and in transferrin receptor mRNA. Iron-responsive element (IRE)-regulated divalent metal transporter 1 (DMT1) increased in maternal and neonatal liver. Non-IRE-regulated DMT1 levels did not change in the maternal liver, but decreased in the neonatal liver. H and L ferritin mRNA levels also showed different patterns in the mother and her offspring. Finally, the neonatal size correlated with maternal Fe stores, and not with those of the fetus. The data demonstrate that Fe supplementation during pregnancy is most effective when given early, rather than later, in gestation. PMID:15358806

Gambling, L; Andersen, H S; Czopek, A; Wojciak, R; Krejpcio, Z; McArdle, H J

2004-11-15

234

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. PMID:23736656

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

2013-01-01

235

Long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate on sperm and testicular parameters in Wistar rats offspring  

PubMed Central

Background: Phthalate esters have been shown to cause reproductive toxicity in both developing and adult animals. Objective: This study was designed to assess long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate (DEHP) on reproductive ability of both neonatal and adult male offspring. Materials and Methods: 60 female rats randomly divided in four equal groups; vehicle control and three treatment groups that received 10, 100 and 500 mg/kg/day DEHP via gavage during gestation and lactation. At different ages after birth, the volumes of testes were measured by Cavellieri method, testes weights recorded and epididymal sperm samples were assessed for number and gross morphology of spermatozoa. Following tissue processing, seminiferous tubules diameter and germinal epithelium height evaluated with morphometric techniques. Results: Mean testis weight decreased significantly (p<0.05) in 500 mg/kg/day dose group from 28 to 150 days after birth. Significant decreases were seen in total volumes of testis in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups until 150 days after birth. Seminiferous tubules diameter and germinal epithelium height decreased significantly in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups during postnatal development. Also, mean sperm density in 100 mg/kg/day (p<0.05) and 500 mg/kg/day (p<0.01) doses groups and percent of morphologically normal sperm in highest dose group (p<0.05) decreased significantly until 150 days after birth. Conclusion: Present study showed that maternal exposure to Di (2-ethylhexyl) Phthalate during gestation and lactation caused to permanent and dose-related reductions of sperm and testicular parameters in rats offspring. PMID:25242968

Dorostghoal, Mehran; Moazedi, Ahmad Ali; Zardkaf, Adel

2012-01-01

236

Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation.  

PubMed

Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2(+) progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling(+) apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing ?-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300ppm HCP. Neurogenesis may be affected by dysfunction of cholinergic inputs into granule cell lineages and/or GABAergic interneurons as indicated by decreased transcript levels of Chrnb2 and numbers of Chrnb2(+) interneurons caused by myelin vacuolation in the septal-hippocampal pathway. PMID:25497112

Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

2015-02-01

237

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat  

SciTech Connect

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 {mu}g/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis.

Kransler, Kevin M. [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States)], E-mail: kransler@buffalo.edu; Tonucci, David A. [Givaudan Flavors Corp., 1199 Edison Drive, Cincinnati, OH 45216 (United States)], E-mail: david.tonucci@givaudan.com; McGarrigle, Barbara P. [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States)], E-mail: bpmg@buffalo.edu; Napoli, Joseph L. [Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA 94720 (United States)], E-mail: jna@berkeley.edu; Olson, James R. [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States)], E-mail: jolson@buffalo.edu

2007-10-01

238

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

PubMed

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. PMID:23107313

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

2013-07-01

239

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. PMID:23107313

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

2013-01-01

240

Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: modulation by folic acid supplementation.  

PubMed

Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5 mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine. PMID:24583191

Toffoli, L V; Rodrigues, G M; Oliveira, J F; Silva, A S; Moreira, E G; Pelosi, G G; Gomes, M V

2014-05-15

241

Influence of maternal ingestion of Aroclor 1254[reg sign] (PCB) or FireMaster BP-6[reg sign] (PBB) on unstimulated and stimulated corticosterone levels in young rats  

SciTech Connect

The organohalides polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) remain troublesome environmental pollutants. For example, the percentage of the population in which PCB is detectable in adipose tissue remains high. These compounds are of particular interest to residents of the North Central United States, especially in regions surrounding the Great Lakes where contaminated fish may be a regular component of the diet. Additionally, PBB was mistakenly fed to cattle and chickens in Michigan during the early 1970s, products of which were ingested by humans. Among the physiological effects of ingestion of PCB or PBB is the depression of thyroid status, which has been reported in adult humans, in adult experimental animals, and in the offspring of these animals. In adult rats, circulating levels of thyroid hormones are inversely proportional to dose of PCB or PBB in the diet. On the other hand, reports of effects of these organohalides on adrenocortical function remain equivocal, describing both PCB- and PBB-induced depression, and absence of effect in rats and monkeys. Despite the possible consequences of maternal ingestion of PCB or PBB on future generations, little work has been done previously to determine whether consumption of these materials by pregnant and lactating animals confers hypothyroidism on their offspring, and/or influences other mechanisms of endocrine control in the young. Since early studies showed that hypothyroidism induced by feeding pregnant rats the goitrogen thiouracil altered the functional capabilities in their young of the hypothalamus-pituitary-adrenal (HPA) axis, as revealed by circulating corticosterone levels, the present study was done to determine whether ingestion of either PCB (Aroclor 1254[reg sign]) or PBB (FireMaster BP-6[reg sign]) by pregnant and lactating rats resulted in depressed thyroid status and/or modified HPA axis function in their 15 day old young. 19 refs., 1 fig., 1 tab.

Meserve, L.A.; Murray, B.A.; Landis, J.A. (Bowling Green State Univ., Bowling Green, OH (United States))

1992-05-01

242

Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and astrogliosis in the hypothalamus of the adult rat offspring.  

PubMed

The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and ?-melanocyte-stimulating hormone (?-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82 % in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and ?-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model. PMID:25609154

Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Peixoto-Silva, Nayara; de Oliveira, Elaine; Lisboa, Patricia C

2015-02-01

243

Variable Maternal Stress in Rats Alters Locomotor Activity, Social Behavior, and Recognition Memory in the Adult Offspring  

PubMed Central

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.

2013-01-01

244

Involvement of the strychnine-sensitive glycine receptor in the anxiolytic effects of GlyT1 inhibitors on maternal separation-induced ultrasonic vocalization in rat pups.  

PubMed

Several studies have shown that glycine transporter 1 (GlyT1) inhibitors have anxiolytic actions. There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions of GlyT1 inhibitors is yet to be determined. Here, we clarified which glycine receptor is the main contributor to the anxiolytic effects of GlyT1 inhibitors by using maternal separation-induced ultrasonic vocalization (USV) by rat pups as an index of anxiety. We confirmed that administration of the benzodiazepine diazepam or the selective serotonin reuptake inhibitor escitaloplam, which are both clinically proven anxiolytics, or the GlyT1 inhibitor SSR504734 (2-chloro-N-[(S)-phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide), decreases USV in rat pups. In addition, we showed that another GlyT1 inhibitor, ALX5407 ((R)-N-[3-(4'-fluorophenyl)-3(4'-phenylphenoxy)propyl]sarcosine) also decreases USV in rat pups. SSR504734- or ALX5407-induced decreases in USV were dose-dependently reversed by administration of the GlyA antagonist strychnine, whereas the diazepam- or escitalopram-induced decreases in USV were not. Furthermore, GlyT1-induced decreases in USV were not reversed by administration of the GlyB antagonist L-687,414. Together, these results suggest that GlyA activation is the main contributor to the anxiolytic actions of GlyT1 inhibitors and that the anxiolytic actions of diazepam and escitalopram cannot be attributed to GlyA activation. Our findings provide new insights into the importance of the activation of GlyA in the anxiolytic effects of GlyT1 inhibitors. PMID:25435080

Komatsu, Hiroko; Furuya, Yoshiaki; Sawada, Kohei; Asada, Takashi

2015-01-01

245

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. PMID:24831231

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

2014-01-01

246

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. PMID:23785432

Wang, Hong; Gondré-Lewis, Marjorie C.

2013-01-01

247

Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats.  

PubMed

Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic ?-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes. PMID:24523338

Tran, Melanie; Gallo, Linda A; Hanvey, Alanna N; Jefferies, Andrew J; Westcott, Kerryn T; Cullen-McEwen, Luise A; Gardner, David K; Moritz, Karen M; Wlodek, Mary E

2014-04-15

248

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. PMID:23926548

Yakubu, Musa Toyin; Musa, Isa Fakai

2012-01-01

249

Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.  

PubMed

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

2014-03-01

250

The effect of a prolonged magnesium restriction on the humoral immune response in maternal rats and their offspring  

E-print Network

weight of rat dams during lactation. . . 31 Table 7 Body weight of pups during lactation as affected by dietary treat. ment of rat dams 34 Table 8 1", ineral composition of femurs of rat dans as affect. ed by dietary treatment. 3 r Tab 1 e 9... ~'Dc CD g) g 0 CD 8 8 03 C ~ U) 0 -'c7) C 0 Q ~ g) v ID Q) v- s- C CO W ca g~& C ~ ECC OC 2, v= i '2& 0 I (73m Q& 5 Q) v mE~ 0 M g (Q C. (0 C &eC IJJ ~ co ~~ ~E cn &D y ID LL 0 0 a) 0~ 27 0 CU W IH S tD rd 0 Cd O O O O ?4 0...

Cohill, Diane T

2012-06-07

251

Interfering With Somatosensory Stimulation From Pups Sensitizes Experienced, Postpartum Rat Mothers to Oxytocin Antagonist Inhibition of Maternal Behavior  

Microsoft Academic Search

Proximal separation (PS) refers to isolating pups in small cages so dams can hear, smell, and see pups but have very limited physical contact with them. Six days of PS diminished the number of discernible oxytocin-(OT) immunostaining perikarya in forebrain areas of rat dams compared with 6 days of total separation (TS) or no separation (NS) from pups. Dams exhibited

C. A. Pedersen; J. M. Johns; I. Musiol; M. Perez-Delgado; G. Ayers; B. Faggin; J. D. Caldwell

1995-01-01

252

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

PubMed

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

2013-12-01

253

EFFECTS OF MATERNAL FOOD RESTRICTION ON FETAL LUNG EXTRACELLULAR MATRIX DEPOSITION AND LONG TERM PULMONARY FUNCTION IN AN EXPERIMENTAL RAT MODEL  

PubMed Central

Intrauterine growth restriction (IUGR) increases the risk of respiratory compromise throughout postnatal life. However, the molecular mechanism(s) underlying the respiratory compromise in offspring following IUGR is not known. We hypothesized that IUGR following maternal food restriction (MFR) would affect extracellular matrix deposition in the lung, explaining the long-term impairment in pulmonary function in the IUGR offspring. Using a well-established rat model of MFR during gestation to produce IUGR pups, we found that at postnatal day 21, and at 9 months of age the expression and abundance of elastin and alpha smooth muscle actin (?SMA), two key extracellular matrix proteins, were increased in IUGR lungs when compared to controls (p<0.05, n = 6), as determined by both Western and immunohistochemistry analyses. Compared to controls, the MFR group showed no significant change in pulmonary resistance at baseline, but did have significantly decreased pulmonary compliance at 9 months (p<0.05 vs control, n=5). In addition, MFR lungs exhibited increased responsiveness to methacholine challenge. Furthermore, exposing cultured fetal rat lung fibroblasts to serum deprivation increased the expression of elastin and elastin-related genes, which was blocked by serum albumin supplementation, suggesting protein deficiency as the predominant mechanism for increased pulmonary elastin deposition in IUGR lungs. We conclude that accompanying the changes in lung function, consistent with bronchial hyperresponsiveness, expression of the key alveolar extracellular matrix proteins elastin and ?SMA increased in the IUGR lung, thus providing a potential explanation for the compromised lung function in IUGR offspring. PMID:22058072

Rehan, Virender K.; Sakurai, Reiko; Li, Yishi; Karadag, Ahmet; Corral, Julia; Bellusci, Saverio; Xue, Ying Ying; Belperio, John; Torday, John S.

2011-01-01

254

Maternal immunization.  

PubMed

Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

Moniz, Michelle H; Beigi, Richard H

2014-09-01

255

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring.  

PubMed

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor. PMID:19553280

Oliveira, E; Moura, E G; Santos-Silva, A P; Fagundes, A T S; Rios, A S; Abreu-Villaça, Y; Nogueira Neto, J F; Passos, M C F; Lisboa, P C

2009-09-01

256

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

PubMed

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

2013-06-01

257

Maternity data.  

PubMed

Statistics were provided for 23 districts and 29 hospitals in Uganda, 1992, for the following maternal measures: parity, prenatal care, normal and abnormal deliveries, abortions, maternal mortality, live births, stillbirths, premature births, incidence of low birth weight, immunization status, and contraceptive use. About 60% of districts reported data on the average for 7 months of the year, and 75% of all hospitals reported data to districts. The data were considered incomplete, inconsistent, and inaccurate. In 1992, 63,691 mothers sought maternity services, of whom 75% attended prenatal care. Districts with high prenatal care use included Pallisa, Jinja, Kiboga, Kalangala, and Kibale. Low prenatal care was reported in Kabarole, Kasese, and Iganga. 32,873 deliveries were reported, of which 8.8% were abnormal. High rates of abnormal deliveries were from hospitals in Villa, Maria, Kitovu, and Matany, all nongovernmental organization hospitals. Low rates were reported from Mbale (2.9%), Jinja (0.8%), Masindi (2.8%), Mpigi (0.4%), and Kalangala (0%). Six hospitals reported abnormal deliveries ranging between 3 and 5%. All other hospitals had percentages greater than 14%. The maternal mortality rate was high at 600/100,000 and highest in Kapchorwa (5600/100,000), which could have been due to effective referral. 13.7% of births were low birth weight (2500 g). Low birth weight was highest in Mubende (26.7%), Moroto (25.8%), Kitgum (21.5%), Kapchorwa (20.3%), and Kasese (20.0%). Districts with low percentages of low birth weight babies included Bushenyi (4.7%), Iganga (5.9%), Kiboga (6.2%), Hoima (7.0%), and Kalangala (7.8%). Hospital maternal mortality was 800/1000. A 1993 community survey of 12 districts reported maternal mortality of 525/100,000 for the community, 600/100,000 for health units, and 800/100,000 for hospitals. BCG and polio immunization were highest in Kalangala and Hoima districts. PMID:12288707

1994-01-01

258

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. PMID:18342837

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

2009-01-01

259

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

Microsoft Academic Search

Non-allogeneic factors such as increased nephron “workload” may contribute to chronic renal allograft rejection. Reducing\\u000a dietary protein from 20 % to 8 % was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient,\\u000a “tolerised” by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance\\u000a were similar for both groups at all

Athena Bombas; Alicia N. Stein-Oakley; Kirsty Baxter; Napier M. Thomson; Paula Jablonski

1999-01-01

260

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. PMID:23118990

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

2012-01-01

261

Maternal Filicide  

Microsoft Academic Search

Having identified that most violent crime is carried out by men, feminists have recently called attention to the need to also bring a feminist analysis to violent crimes committed by women. This research examines data drawn from coroners court files in Victoria, Australia for the period 1978 to 1991 to explore scenarios of maternal filicide. The data are reviewed in

Christine M. Alder; June Baker

1997-01-01

262

Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition.  

PubMed

Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes. PMID:19339705

Burdge, Graham C; Lillycrop, Karen A; Phillips, Emma S; Slater-Jefferies, Joanne L; Jackson, Alan A; Hanson, Mark A

2009-06-01

263

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. PMID:25003120

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

2014-01-01

264

Prenatal programming of renal sodium handling in the rat.  

PubMed

Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl- co-transporter (NKCC2) and the Na+/Cl- co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na+ excretion rates (1.6+/-0.3 and 3.0+/-0.4 mumol.min-1.100 g-1 of body weight in control male and LP male respectively; P<0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5+/-0.2 and 3.0+/-0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase alpha1 subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4+/-1.8 and 17.7+/-1.2 nmol of phosphate.mug-1 of protein.h-1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the alpha1 subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure-natriuresis mechanism; however, the loss of the Na+/K+ ATPase alpha1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally. PMID:19128240

Alwasel, Saleh H; Ashton, Nick

2009-07-01

265

Opiate Disruption of Maternal Behavior: Morphine Reduces, and Naloxone Restores, c- fos Activity in the Medial Preoptic Area of Lactating Rats  

Microsoft Academic Search

Morphine significantly impairs maternal behavior; naloxone, an opiate antagonist, restores it. Maternal behavior is associated with c-fos expression, an immediate early gene product, in the medial preoptic area (mPOA) of females. In two experiments, the effects of morphine-alone and morphine plus naloxone on the expression of c-fos were examined. On postpartum day 5, females were injected with morphine or saline

Graciela Stafisso-Sandoz; Daniel Polley; Elizabeth Holt; Kelly G Lambert; Craig Howard Kinsley

1998-01-01

266

Early-Life Maternal Separation and Social Isolation Produce an Increase in Impulsive Action but Not Impulsive Choice  

Microsoft Academic Search

Early life environment, events, and context, such as mother–offspring relationship, can have profound effects on future behavior and physiology. We investigated the effects of long-term maternal and social separation, through artificial rearing, on adult impulsivity. Rats were maternally reared (MR) or artificially reared (AR) and half of the AR rats were provided with replacement somatosensory stimulation intended to simulate maternal

Vedran Lovic; Darren Keen; Paul J. Fletcher; Alison S. Fleming

2011-01-01

267

DIBUTYL PHTHALATE: MATERNAL EFFECTS VERSUS FETOTOXICITY (JOURNAL VERSION)  

EPA Science Inventory

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 pregnant rats were used to e...

268

Maternal Obesity at Conception Programs Obesity in the Offspring  

Technology Transfer Automated Retrieval System (TEKTRAN)

The risk of obesity in adult-life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in the offspring, we have developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via ...

269

ORIGINAL ARTICLE Maternal Contact Differentially Modulates Central and Peripheral  

E-print Network

ORIGINAL ARTICLE Maternal Contact Differentially Modulates Central and Peripheral Oxytocin in Rat Sciences, Indiana University, Bloomington, IN, USA. Center for the Integrative Study of Animal Behavior. Oxytocin (OT) is a nonapeptide neurohormone synthesised primarily in the paraventricular nucleus (PVN

Demas, Greg

270

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...

271

Effects of maternal exposure to di-isononylphthalate (DINP) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) on steroidogenesis in the fetal rat testis and adrenal gland.  

PubMed

Exposure to antiandrogens during the critical developmental window (i.e. sexual differentiation) can permanently demasculinize the male phenotype. Here we have investigated the effects of developmental exposure to di-isononylphthalate (DINP) (250 and 750 mg/kg) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) (50 and 100mg/kg) on 19.5-day-old fetal Sprague-Dawley rat testicular and adrenal steroidogenesis. Maternal exposure to DINP or p,p'-DDE on embryonic days (EDs) 13.5-17.5 did not down-regulate the activity of steroidogenesis in ED 19.5 male rat fetus. Protein expression levels of testicular and adrenal StAR, P450scc, 3beta-HSD and androgen receptor (AR) did not show any changes. However, p,p'-DDE caused clear abnormalities in the ultrastructure of steroidogenic cells in ED 19.5 rat testis and adrenal. These structural alterations can disturb the development and function of fetal testis and adrenal that may become evident later in life. PMID:19490997

Adamsson, A; Salonen, V; Paranko, J; Toppari, J

2009-07-01

272

Pups Call, Mothers Rush: Does Maternal Responsiveness Affect the Amount of Ultrasonic Vocalizations in Mouse Pups?  

Microsoft Academic Search

In rats and mice, the ultrasonic vocalizations emitted by pups have been suggested to modulate maternal behavior. In the present study we show that the number of calls emitted by mouse pups can reflect maternal responsiveness. Maternal responsiveness towards pups was evaluated on postnatal day 8 using a three-compartment cage test where the mother, to reach the pups, had to

Francesca R. D’Amato; Elisabetta Scalera; Celeste Sarli; Anna Moles

2005-01-01

273

Effects of maternal and pre-weaning undernutrition in rat offspring: Age at reproductive senescence and intergenerational pup growth and viability  

EPA Science Inventory

Maternal and/or postnatal undernutrition are widespread in human populations and are components of many experimental developmental and reproductive toxicology bio-assays. This study investigated in utero and/or pre-weaning undernutrition effects on reproductive maturation and se...

274

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.  

PubMed

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

2011-01-13

275

Maternal Treatment with Agonistic Autoantibodies against Type-1 Angiotensin II Receptor in Late Pregnancy Increases Apoptosis of Myocardial Cells and Myocardial Susceptibility to Ischemia-Reperfusion Injury in Offspring Rats  

PubMed Central

Epidemiological studies have demonstrated that offspring born to mothers preeclampsia (PE) are at increased risk for developing cardiovascular diseases after birth, but the underlying mechanism is unknown. Angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of the AT1 receptor, is believed to be involved in the pathogenesis of both PE and fetal growth restriction. The aim of the present study was to confirm the hypothesis that prenatal AT1-AA exposure increases the heart susceptibility to ischemia/reperfusion injury (IRI) in the offspring in an AT1-AA-induced animal model of PE, and determine whether or not the increase of maternal AT1-AA level is a factor contributing to sustained abnormalities of the heart structure during infancy. The hearts of 45-day-old offspring rats were studied using Langendorff preparation to determine the susceptibility of the heart to IRI. The results showed that the body weight of the maternal rats was not significantly different between the study and control groups, but the body weight of their offspring in AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3 after birth. Although the heart weight index was not significantly affected at all ages examined, AT1-AA significantly increased the size of myocardial cells of the left ventricle (LV) at the age of 45 days. AT1-AA gained access to fetal circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1-AA also significantly delayed recovery from IRI and affected the LV function of 45-day-old offspring. This was associated with a significant increase in IRI-induced LV myocardial infarct size. These results suggest that AT1-AA induced abnormal apoptosis of fetal myocardial cells during the fetal period and increased the cardiac susceptibility to IRI in adult offspring. PMID:24278308

Wang, Xiaofang; Zheng, Yanqian; Zhang, Qiaoyan; Zhi, Jianming

2013-01-01

276

Neonatal Low-Protein Diet Changes Deiodinase Activities and Pituitary TSH Response to TRH in Adult Rats  

Microsoft Academic Search

Protein malnutrition during neonatal programs for a lower body weight and hyperthyroidism in the adult offspring were ana- lyzed. Liver deiodinase is increased in such animals, contribu- ting to the high serum triiodothyronine (T3) levels. The level of deiodinase activities in other tissues is unknown. We analyzed the effect of maternal protein restriction during lactation on thyroid, skeletal muscle, and

P. C. Lisboa; A. T. S. Fagundes; A. T. A. Denolato; E. Oliveira; I. T. Bonomo; S. B. Alves; F. H. Curty; M. C. F. Passos; E. G. Moura

2008-01-01

277

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

PubMed

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

2013-11-14

278

Development of glial cells cultured from prenatally alcohol treated rat brain: Effect of supplementation of the maternal alcohol diet with a grape extract  

Microsoft Academic Search

The aim of this work was to investigate the effect of supplementation of a maternal alcohol diet with a grape extract on glial\\u000a cell development. Glial cells were cultured during 4 weeks from cortical brain cells of the new born offspring in DMEM medium\\u000a supplemented with fetal calf serum. Enzymatic markers of nerve cell development were measured (enolase isoenzymes and

Marc Ledig; Adam Holownia; Jean-Christophe Copin; Georges Tholey; Irina Anokhina

1996-01-01

279

Is the dietary protein restriction achievable in chronic kidney disease? The impact upon quality of life and the dialysis delay.  

PubMed

The possible deleterious effect of meet consumption upon deterioration of renal disease was speculated from Lionel Beale as early as 1869. The first attempt to apply a very low protein diet in humans is attributed to Millard Smith who prescribed a diet consisting of 300 mg protein per day in a volunteer medical student for 24 days. Unfortunately, in early 20(th) century, prescribing very low protein diets among patients suffering from renal disease complicated with malnutrition and the medical practice of this era turned to the recommendation of high protein diets because it was believed that protein consumption is coupled with the strength of civilized man. In mid sixties Giordano and Giovanetti introduced low protein diets in the treatment of uremic patients but their efforts did not accepted from the medical community. Meanwhile the evolution of haemodialysis, peritoneal dialysis and transplantation as effective methods of treating end stage renal disease guided doctors and patients far from privative diets in the era of plenty. The rapidly increasing number of end stage renal disease patients needed substitution of renal function produced a tremendous increase of financial burden upon public health system expenditure and alternative measures of therapy, prevention and delaying chronic kidney disease searched. Unfortunately MDRD study failed to show convincing results of food protein restriction and blood pressure lowering in ameliorating deterioration of renal function and the majority of physicians turned to the practice of early dialysis in an attempt to avoid malnutrition. Despite the increasing knowledge and the appliance of certain guidelines in treating end stage renal disease patients, the morbidity and mortality remain high among this population. The search toward other possible toxic substances showed that phosphorus consumption with diet is another dangerous element exerting its deleterious effect in deteriorating renal function as well as increasing morbidity and mortality. Recently published epidemiological data suggest a very poor outcome of elderly patients, older than 80 years of age, undergoing substitution of renal function by dialysis or peritoneal dialysis and a lot of skepticism arise concerning the beneficial effect of diet and a rigorous effort of rehabilitation of these patients instead of substitution of renal function by either method. PMID:21897750

Koulouridis, E; Koulouridis, I

2011-01-01

280

Does estrogen affect the development of abnormal vascular function in offspring of rats fed a low-protein diet in pregnancy?  

PubMed

It is established that there are gender-related differences in the effects on offspring blood pressure induced by maternal protein restriction in animal studies. Since such effects may depend on estrogen levels, we hypothesized that lower estrogen would induce an earlier onset of hypertension caused by maternal under-nutrition. Wistar rats were fed a diet containing either 18% (C) or 9% (R) casein throughout pregnancy. Half of the offspring in both C and R groups were ovariectomized on day 50 (CX, RX), and the other half underwent a sham operation (CO, RO). On d 175, offspring were killed for small artery reactivity and histologic investigation. Birth weight and later growth were not significantly different between C and R. RX had higher systolic blood pressure than CX on d125, but no difference was seen between RO and CO. On d 175, systolic blood pressure was higher in R than in C, whether or not ovariectomized. Dilator responses to acetylcholine and bradykinin in small mesenteric arteries were significantly attenuated in RX, although responses to SNP and isoprenaline showed no attenuation in R. The ratio of coronary peri-vascular fibrosis to total vascular area was higher in R, and the fibrosis became prominent in ovariectomized rats. These findings suggest that estrogen plays an important role in limiting the elevation of offspring blood pressure induced by maternal under-nutrition, possibly via BK-mediated mechanisms. The processes may underlie gender and life course patterns of hypertension and also the developmental origins of this disease. PMID:16641213

Musha, Yuka; Itoh, Shigeru; Hanson, Mark A; Kinoshita, Katsuyuki

2006-06-01

281

Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats  

PubMed Central

Our earlier studies have shown that the artificial rearing of newborn rat pups [first generation high carbohydrate (1-HC)] on an HC milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring [second-generation HC (2-HC)] of 1-HC female rats spontaneously acquired the HC phenotype in the postweaning period. In this study, we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on laboratory chow and increased body weight gain beginning from the immediate postweaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain and increased plasma levels of insulin, leptin, proinflammatory markers, and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with those of control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring. PMID:18682533

Srinivasan, Malathi; Dodds, Catherine; Ghanim, Husam; Gao, Tao; Ross, Peter J.; Browne, Richard W.; Dandona, Paresh; Patel, Mulchand S.

2008-01-01

282

Maternal and Child nutrition  

E-print Network

Maternal and Child nutrition Earn an advanced degree in a highly specialized field Taught #12;Courses: Nutrition During Pregnancy Lactation and Infant Nutrition Child and Adolescent Nutrition Applied Research Methods in Maternal and Child Nutrition Topics in Epidemiology of Maternal and Child

Schladow, S. Geoffrey

283

Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring.  

PubMed

Intrauterine undernutrition plays a role in the development of adult hypertension. Most studies are done in male offspring to delineate the mechanisms whereby blood pressure may be raised; however, the vascular mechanisms involved in female offspring are unclear. Female offspring of pregnant Sprague-Dawley rats fed either a control (C; 18%) or a low-protein (LP; 6%) diet during pregnancy were used. Birth weight and later growth were markedly lower in LP than in C offspring. LP offspring exhibited impaired estrous cyclicity with increased mean arterial pressure. Hypotensive response to acetylcholine (ACh) and the hypertensive response to phenylephrine (PE) were greater in LP than in C rats. N-nitro-L-arginine methyl ester (L-NAME) induced greater hypertensive responses in C than in LP rats. Endothelium-intact mesenteric arteries from LP offspring exhibited increased contractile responses to PE and reduced vasodilation in response to ACh. In endothelium-denuded arteries, relaxation responses to sodium nitroprusside were similar in both groups. Basal and ACh-induced increase in vascular nitrite/nitrate production was lower in LP than in C offspring. L-NAME or 1H-1,2,4-oxadiazolo-4,3-quinoxalin-1-one inhibited ACh relaxations and enhanced PE contractions in C offspring, but had minimal effect in LP rats. The decreased NO-mediated vascular response might explain the increased vascular contraction and arterial pressure in female offspring with low birth weight. PMID:18957856

Sathishkumar, Kunju; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

2009-01-01

284

Accelerated maternal responding following intra-VTA pertussis toxin treatment.  

PubMed

Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 ?g/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor. PMID:21571006

Byrnes, John J; Gleason, Erin D; Schoen, Mathew T; Lovelock, Dennis F; Carini, Lindsay M; Byrnes, Elizabeth M; Bridges, Robert S

2011-10-01

285

Accelerated Maternal Responding Following Intra-VTA Pertussis Toxin Treatment  

PubMed Central

Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 ?g/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor. PMID:21571006

Byrnes, John J.; Gleason, Erin D.; Schoen, Mathew T.; Lovelock, Dennis F.; Carini, Lindsay M.; Byrnes, Elizabeth M.; Bridges, Robert S.

2011-01-01

286

Protein restriction cycles reduce IGF-1 and phosphorylated Tau, and improve behavioral performance in an Alzheimer’s disease mouse model  

PubMed Central

Summary In laboratory animals, calorie restriction (CR) protects against aging, oxidative stress, and neurodegenerative pathologies. Reduced levels of growth hormone and IGF-1, which mediate some of the protective effects of CR, can also extend longevity and/or protect against age-related diseases in rodents and humans. However, severely restricted diets are difficult to maintain and are associated with chronically low weight and other major side effects. Here we show that 4 months of periodic protein restriction cycles (PRCs) with supplementation of nonessential amino acids in mice already displaying significant cognitive impairment and Alzheimer’s disease (AD)-like pathology reduced circulating IGF-1 levels by 30–70% and caused an 8-fold increase in IGFBP-1. Whereas PRCs did not affect the levels of ? amyloid (A?), they decreased tau phosphorylation in the hippocampus and alleviated the age-dependent impairment in cognitive performance. These results indicate that periodic protein restriction cycles without CR can promote changes in circulating growth factors and tau phosphorylation associated with protection against age-related neuropathologies. PMID:23362919

Parrella, Edoardo; Maxim, Tom; Maialetti, Francesca; Zhang, Lu; Wan, Junxiang; Wei, Min; Cohen, Pinchas; Fontana, Luigi; Longo, Valter D.

2014-01-01

287

Adverse cardiac remodeling due to maternal low protein diet is associated with alterations in expression of genes regulating glucose metabolism  

Microsoft Academic Search

Background and aimsWe have previously shown that a maternal low protein (LP) diet during pregnancy in the rat results in adverse ventricular remodeling and contractile deficiencies of the neonatal rat heart. Since pathological cardiac hypertrophy is associated with increased expression of genes involved in glucose handling, this study was undertaken to examine if maternal LP diet alters the expression of

P. S. Tappia; C. Guzman; L. Dunn; N. Aroutiounova

288

Early-Life Maternal Separation and Social Isolation Produce an Increase in Impulsive Action but Not Impulsive Choice  

E-print Network

Early-Life Maternal Separation and Social Isolation Produce an Increase in Impulsive Action but Not Impulsive Choice Vedran Lovic and Darren Keen University of Toronto Mississauga Paul J. Fletcher University impulsivity. Rats were maternally reared (MR) or artificially reared (AR) and half of the AR rats were

Sokolowski, Marla

289

Affective, cognitive, and motivational processes of maternal care.  

PubMed

The present chapter reviews current knowledge of the neurobiology of maternal behavior in mammals. In the first section, we present existing information of the affective, motivational, and cognitive processes that characterize maternal behavior, primarily discussing research findings in rats and humans, because most of the work on the neurobiological basis of this behavior has been done in these species. The second section outlines the maternal neural circuitry, with a special emphasis on the mechanisms that underlie the affective, motivational, and cognitive processes of motherhood. Finally, we summarize some of the main themes raised in the chapter and issues yet to be explored. PMID:25287542

Pereira, Mariana; Ferreira, Annabel

2015-01-01

290

Foetal life protein restriction in male mink (Neovison vison) kits lowers post-weaning protein oxidation and the relative abundance of hepatic fructose-1,6-bisphosphatase mRNA.  

PubMed

Foetal life malnutrition has been studied intensively in a number of animal models. Results show that especially foetal life protein malnutrition can lead to metabolic changes later in life. This might be of particular importance for strict carnivores, for example, cat and mink (Neovison vison) because of their higher protein requirement than in other domestic mammals. This study aimed to investigate the effects of low protein provision during foetal life to male mink kits on their protein metabolism during the early post-weaning period of rapid growth and to investigate whether foetal life protein deficiency affects the response to adequate or deficient protein provision post weaning. Further, we intended to study whether the changes in the gene expression of key enzymes in foetal hepatic tissue caused by maternal protein deficiency were manifested post-weaning. A total of 32 male mink kits born to mothers fed either a low-protein diet (LP), that is, 14% of metabolizable energy (ME) from protein (foetal low - FL), n = 16, or an adequate-protein (AP) diet, that is, 29% of ME from protein (foetal adequate - FA), n = 16) in the last 16.3 ± 1.8 days of pregnancy were used. The FL offspring had lower birth weight and lower relative abundance of fructose-1,6-bisphosphatase (Fru-1,6-P2ase) and pyruvate kinase mRNA in foetal hepatic tissue than FA kits. The mothers were fed a diet containing adequate protein until weaning. At weaning (7 weeks of age), half of the kits from each foetal treatment group were fed an AP diet (32% of ME from protein; n = 8 FA and 8 FL) and the other half were fed a LP diet (18% of ME from protein; n = 8 FA and 8 FL) until 9.5 weeks of age, yielding four treatment groups (i.e. FA-AP, FA-LP, FL-AP and FL-LP). Low protein provision in foetal life lowered the protein oxidation post-weaning compared with the controls (P = 0.006), indicating metabolic flexibility and a better ability to conserve protein. This could not, however, be supported by changes in liver mass because of foetal life experience. A lower relative abundance of Fru-1,6-P2ase mRNA was observed (P < 0.05), being lower in 9.5-week-old FL than in FA kits. It can be concluded that foetal life protein restriction leads to changes in post-weaning protein metabolism through lower protein oxidation of male mink kits. PMID:22436154

Matthiesen, C F; Blache, D; Thomsen, P D; Tauson, A-H

2012-01-01

291

Gestational changes in calbindin-D9k in rat uterus, yolk sac, and placenta: implications for maternal-fetal calcium transport and uterine muscle function.  

PubMed Central

Calbindin-D9k was quantified and its cellular location was defined in uterus, yolk sac, and placenta. In late gestation (days 17 to term) coordinated induction of calbindin-D9k was seen in uterine epithelial lining cells and juxtaposed yolk sac visceral epithelium as well as the intraplacental yolk sac epithelium. The induction of calbindin-D9k in these cells coincided with the time of exponential fetal bone growth and maximal fetal accumulation of calcium, suggesting a role of the protein in these epithelial layers in maternal-fetal calcium transport. Dynamic changes also occurred in the calbindin-D9k contents of the two layers of uterine smooth muscle (outer longitudinal and inner circular) during mid- and late gestation. During early pregnancy (days 0-4), calbindin-D9k was present in the two smooth muscle layers. By midgestation (day 10), calbindin-D9k had decreased by a factor of 10 in these tissue layers. During late gestation calbindin-D9k rebounded in the inner circular smooth muscle layer. These uterine changes of early and midgestation were reproduced by the endocrine changes of pseudopregnancy. Progesterone appeared to be a good candidate for controlling the midgestational decrease of uterine muscle calbindin-D9k, as it blunted estrogen's induction of the protein in the muscle layers and stroma in a dose-dependent manner. Changes in myometrial calbindin-D9k may reflect variations in muscular calcium storage, thereby representing alterations in potential for contraction. Images PMID:2717621

Mathieu, C L; Burnett, S H; Mills, S E; Overpeck, J G; Bruns, D E; Bruns, M E

1989-01-01

292

Effect of acute ethanol administration on diamine oxidase activity in maternal, embryonal and fetal tissues  

Microsoft Academic Search

Pregnant rats were acutely treated with ethanol to study the influence of this drug on diamine oxidase activity of maternal, embryonal, and fetal tissues. When ethanol was given on day 12 of gestation, enzyme activity was unmodified in placenta and embryo, whereas it was reduced by 38 and 31%, respectively, in maternal liver and plasma at 3 h. When ethanol

A. Sessa; M. A. Desiderio; A. Perin

1987-01-01

293

Developmental Timing of the Effects of Maternal Care on Gene Expression and Epigenetic Regulation  

E-print Network

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-associated increases in oxytocin receptor mRNA levels were observed beyond the weaning period. Quantification of ER

Champagne, Frances A.

294

Early renal structure alteration in rat offspring from dams fed low protein diet  

Microsoft Academic Search

To investigate the early renal alterations due to severe maternal protein restriction (MPR) Wistar dams received 23% (normal protein, NP) or 5% (low protein, LP) chow during gestation and lactation periods. In NP offspring at birth, the cortex-to-medulla (C\\/M) ratio was 35% greater in female than in male offspring and the mature\\/immature glomeruli ratio was lower in both sexes of

Karla Maria Pereira Pires; Marcia Barbosa Aguila; Carlos Alberto Mandarim-de-Lacerda

2006-01-01

295

How the Kidney Is Impacted by the Perinatal Maternal Environment to Develop Hypertension1  

PubMed Central

ABSTRACT Environmental conditions during perinatal development such as maternal undernutrition, maternal glucocorticoids, placental insufficiency, and maternal sodium overload can program changes in renal Na+ excretion leading to hypertension. Experimental studies indicate that fetal exposure to an adverse maternal environment may reduce glomerular filtration rate by decreasing the surface area of the glomerular capillaries. Moreover, fetal responses to environmental insults during early life that contribute to the development of hypertension may include increased expression of tubular apical or basolateral membrane Na+ transporters and increased production of renal superoxide leading to enhanced Na+ reabsorption. This review will address the role of these potential renal mechanisms in the fetal programming of hypertension in experimental models induced by maternal undernutrition, fetal exposure to glucocorticoids, placental insufficiency, and maternal sodium overload in the rat. PMID:24227755

Paixão, Ana D.; Alexander, Barbara T.

2013-01-01

296

Maternal Stress Induces Adult Reduced REM sleep and Melatonin Level  

PubMed Central

Objectives We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Design Adult male Sprague Dawley rats were treated with either MD or MC procedures for ten days starting at postnatal day 4. At three months of age, sleep was recorded for 48 hours in one set of MD and MC rats while another set of MD and MC rats were measured for locomotor activity (under LD=12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Results Compared with the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared with the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Conclusion Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein. PMID:21805687

Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Guo, Yang

2013-01-01

297

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. PMID:23918394

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

2013-01-01

298

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. PMID:21255612

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

299

Maternal taurine supplementation attenuates maternal fructose-induced metabolic and inflammatory dysregulation and partially reverses adverse metabolic programming in offspring.  

PubMed

Excessive fructose consumption is associated with insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), and high fructose intake during pregnancy can lead to compromised fetal development in the rat. Evidence suggests that the amino acid taurine can ameliorate fructose-induced IR and NAFLD in nonpregnant animals. This study investigated the efficacy of taurine supplementation on maternal fructose-induced metabolic dysfunction and neonatal health. Time-mated Wistar rats were randomized to four groups during pregnancy and lactation: (a) control diet (CON), (b) CON supplemented with 1.5% taurine in drinking water (CT), (c) CON supplemented with fructose solution (F) and (d) F supplemented with taurine (FT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analyzed. Maternal hyperinsulinemia, increased homeostasis model assessment of IR indices and elevated proinflammatory cytokines were observed in F group and normalized in FT group. Maternal fructose-induced hepatic steatosis accompanied with increased liver weight was ameliorated with taurine supplementation. Maternal hepatic sterol regulatory element-binding protein-1c and fatty acid synthase expression was significantly increased in the F group compared to the CON, CT and FT groups. Neonatal hepatic phosphoenolpyruvate carboxykinase expression was increased in male F neonates compared to the CON, CT and FT groups and was increased in female F and FT neonates compared to CON and CT. Interleukin-1? expression was decreased in male CT and FT neonates compared to other male groups. Hepatic tumour necrosis factor receptor-1 was lower in the male FT group than the F group. These results demonstrate that maternal taurine supplementation can partially reverse fructose-induced maternal metabolic dysfunction and may ameliorate adverse developmental programming effects in offspring in a sex-specific manner. PMID:25576095

Li, M; Reynolds, C M; Sloboda, D M; Gray, C; Vickers, M H

2015-03-01

300

Maternal Sexuality and Breastfeeding  

ERIC Educational Resources Information Center

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…

Bartlett, Alison

2005-01-01

301

The politics of maternity.  

PubMed

Changes in the culture of health care require that, to be effective, midwifery practice should become more woman-centred. This may be facilitated by adopting a stronger community orientation. In this way the hegemony of maternity care may be addressed. This paper seeks to draw readers' attention to political developments and to inspire midwives to greater awareness and, possibly, activity. PMID:24600828

Mander, Rosemary; Edwards, Nadine; McHugh, Nessa; Murphy-Lawless, Jo; Patterson, Jenny

2014-02-01

302

Maternity Leave in Taiwan  

ERIC Educational Resources Information Center

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…

Feng, Joyce Yen; Han, Wen-Jui

2010-01-01

303

Maternal diabetes, programming of beta-cell disorders and intergenerational risk of type 2 diabetes.  

PubMed

A substantial body of evidence suggests that an abnormal intra-uterine milieu elicited by maternal metabolic disturbances as diverse as malnutrition, placental insufficiency, diabetes and obesity may be able to programme susceptibility of the foetus to later develop chronic degenerative diseases such as obesity, hypertension, cardiovascular diseases and type 2 diabetes (T2D). As insulin-producing cells have been placed centre stage in the development of T2D, this review examines developmental programming of the beta-cell mass (BCM) in various rodent models of maternal protein restriction, calorie restriction, overnutrition and diabetes. The main message is that whatever the initial maternal insult (F0 generation) and whether alone or in combination, it gives rise to the same programmed BCM outcome in the daughter generation (F1). The altered BCM phenotype in F1 females prohibits normal BCM adaptation during pregnancy and, thus, diabetes (gestational diabetes) ensues. This gestational diabetes is then passed from one generation (F1) to the next (F2, F3 and so on). This review highlights a number of studies that have identified epigenetic mechanisms that may contribute to altered BCM development and beta-cell failure, as observed in diabetes. In addition to their role in instilling the programmed defect, these non-genomic mechanisms may also be involved in its intergenerational transmission. PMID:24948417

Chavey, A; Ah Kioon, M-D; Bailbé, D; Movassat, J; Portha, B

2014-11-01

304

Maternal near miss: an indicator for maternal health and maternal care.  

PubMed

Maternal mortality is one of the important indicators used for the measurement of maternal health. Although maternal mortality ratio remains high, maternal deaths in absolute numbers are rare in a community. To overcome this challenge, maternal near miss has been suggested as a compliment to maternal death. It is defined as pregnant or recently delivered woman who survived a complication during pregnancy, childbirth or 42 days after termination of pregnancy. So far various nomenclature and criteria have been used to identify maternal near-miss cases and there is lack of uniform criteria for identification of near miss. The World Health Organization recently published criteria based on markers of management and organ dysfunction, which would enable systematic data collection on near miss and development of summary estimates. The prevalence of near miss is higher in developing countries and causes are similar to those of maternal mortality namely hemorrhage, hypertensive disorders, sepsis and obstructed labor. Reviewing near miss cases provide significant information about the three delays in health seeking so that appropriate action is taken. It is useful in identifying health system failures and assessment of quality of maternal health-care. Certain maternal near miss indicators have been suggested to evaluate the quality of care. The near miss approach will be an important tool in evaluation and assessment of the newer strategies for improving maternal health. PMID:25136152

Chhabra, Pragti

2014-07-01

305

Maternal Near Miss: An Indicator for Maternal Health and Maternal Care  

PubMed Central

Maternal mortality is one of the important indicators used for the measurement of maternal health. Although maternal mortality ratio remains high, maternal deaths in absolute numbers are rare in a community. To overcome this challenge, maternal near miss has been suggested as a compliment to maternal death. It is defined as pregnant or recently delivered woman who survived a complication during pregnancy, childbirth or 42 days after termination of pregnancy. So far various nomenclature and criteria have been used to identify maternal near-miss cases and there is lack of uniform criteria for identification of near miss. The World Health Organization recently published criteria based on markers of management and organ dysfunction, which would enable systematic data collection on near miss and development of summary estimates. The prevalence of near miss is higher in developing countries and causes are similar to those of maternal mortality namely hemorrhage, hypertensive disorders, sepsis and obstructed labor. Reviewing near miss cases provide significant information about the three delays in health seeking so that appropriate action is taken. It is useful in identifying health system failures and assessment of quality of maternal health-care. Certain maternal near miss indicators have been suggested to evaluate the quality of care. The near miss approach will be an important tool in evaluation and assessment of the newer strategies for improving maternal health. PMID:25136152

Chhabra, Pragti

2014-01-01

306

Maternal ingestion of locoweed  

Microsoft Academic Search

This study investigated whether exposure of ewes to locoweed (Oxytropis sericea; Leguminosae) during gestation would affect ewe behaviour during parturition, ewe–lamb bonding and related behaviours postpartum, and maternal responsiveness of ewes to alien and own lambs. Twenty-nine nulliparous Columbia-Targhee ewes bearing a single fetus were divided into two feeding treatments: (1) locoweed (L, n=15), fed as a 10% locoweed pellet

J. A. Pfister; J. B. Astorga; K. E. Panter; B. L. Stegelmeier; R. J. Molyneux

2006-01-01

307

Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ER?, ER?), oxytocin and serotonin (5-HT1A) in their brain.  

PubMed

In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ER?, ER?), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ER? and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ER? levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety. PMID:25486578

Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

2015-02-01

308

Society for Maternal-Fetal Medicine  

MedlinePLUS

... 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 ...

309

Maternal Depression, Maternal Expressed Emotion, and Youth Psychopathology  

ERIC Educational Resources Information Center

Across development, maternal depression has been found to be a risk factor for youth psychopathology generally and youth depression specifically. Maternal Expressed Emotion (EE) has been examined as a predictor of outcome among youth with depression. The present study explored the associations between youth psychopathology and two…

Tompson, Martha C.; Pierre, Claudette B.; Boger, Kathryn Dingman; McKowen, James W.; Chan, Priscilla T.; Freed, Rachel D.

2010-01-01

310

Child Health, Maternal Marital and Socioeconomic Factors, and Maternal Health  

ERIC Educational Resources Information Center

Although maternal socioeconomic status and health predict in part children's future health and socioeconomic prospects, it is possible that the intergenerational association flows in the other direction such that child health affects maternal outcomes. Previous research demonstrates that poor child health increases the risk of adverse…

Garbarski, Dana; Witt, Whitney P.

2013-01-01

311

Transitioning to Family Centered Maternity Care from Traditional Maternity Care  

Microsoft Academic Search

United States perinatal statistics indicate that maternity care needs improvement. In this evidence-based project, guided by the promoting action on research implementation in health services (PARIHS) framework, it is posited that no practice change will occur unless nurses understand and appreciate the relevance of evidence-based maternity care. A within-group design was used to address the clinical question, \\

Kathleen Kleefisch

2011-01-01

312

Epigenetic Upregulation of Corticotrophin-Releasing Hormone Mediates Postnatal Maternal Separation-Induced Memory Deficiency  

PubMed Central

Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH) in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder. PMID:24718660

Wang, Aiyun; Nie, Wenying; Li, Haixia; Hou, Yuhua; Yu, Zhen; Fan, Qing; Sun, Ruopeng

2014-01-01

313

Maternal Filicide in Turkey.  

PubMed

Filicide occurs in every socioeconomic stratum around the world. This study was conducted to evaluate motives, psychopathological aspects, and socio-demographic factors of 74 filicide cases of women in Turkey. Mean age of mothers, most of whom committed infanticide, was 26 years, and breakdown of criminal offenses are as follows: "to get rid of unwanted babies" (24.3%), "acute psychotic-type filicide" (21.6%), "fatal child abuse and neglect" (17.6%), "to get revenge" (12.2%), "protect the lonely child from the harm and badness after suicide" (10.8%), and "pity" (9.5%) motives. Results showed that maternal filicide cannot be reduced to only mental instability or environmental factors and indicates deficiencies in the capacity of the mothers' role in connecting with their child and with parenting skills. Finally, with regard to defendants' motives, similar factors that contribute to committing maternal filicide should be considered while making an assessment of the data and determining employee risk groups. PMID:25066272

Eke, Salih Murat; Basoglu, Saba; Bakar, Bulent; Oral, Gokhan

2014-07-28

314

Electrophoretic Analysis of the Sera of Young Rats  

Microsoft Academic Search

The absorption of maternal antibodies by the gut of the young rat continues for 20 days after birth and then ceases abruptly. The sera of rats at different ages during and after the absorptive period were examined electrophoretically and ultracentrifugally to determine the changes in the serum proteins during this period. The serum protein of rats of all age groups

R. Halliday; R. A. Kekwick

1957-01-01

315

Impulsive Rats are Less Vedran Lovic1  

E-print Network

Impulsive Rats are Less Maternal Vedran Lovic1 Daniela J. Palombo2 Alison S. Fleming3 1 Department(1), 11­42]. We also found that AR rats are more action impulsive and have reduced attentional capacities] Behavioural Brain Research 148: 209­219]. However, it is unknown whether increased impulsivity contributes

Sokolowski, Marla

316

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. PMID:23460795

Nascimento, Elizabeth; Guzman-Quevedo, Omar; Delacourt, Nellie; da Silva Aragão, Raquel; Perez-Garcia, Georgina; de Souza, Sandra Lopes; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco; Kaeffer, Bertrand

2013-01-01

317

Fetal growth retardation associated with maternal administration of immunosuppressive drugs.  

PubMed

Since maternal-fetal immunogenetic disparity facilitates growth of the fetoplacental unit, nonspecific depression of the maternal immune system by immunosuppressive drugs could result in previously unrecognized adverse effects such as fetal growth retardation. To test this hypothesis, groups of 6 to 8 primigravid Fischer female rats mated with DA or Fischer male rats were treated with saline (controls) or either cyclophosphamide (Cytoxan) or azathioprine (Imuran) in doses similar to those used therapeutically in human subjects. It was found that these drugs caused an increased incidence of fetal death and produced fetal and neonatal growth retardation. Smaller placentas and fetuses reflected a decrease in cell number rather than cell size whereas water, fat, and protein content were only minimally affected. Analyses of mean maternal weight gain, spleen weight assays, and changes in the lymph nodes draining the uterus indicate that effects detrimental to the offspring are primarily the result of immunologic and cytotoxic mechanisms. Moreover, a review of the literature suggests that these immunosuppressive agents are also associated with small-for-gestational age infants in human pregnancies. PMID:879225

Scott, J R

1977-07-15

318

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)

2006-11-13

319

Maternal and Child Health Bureau  

MedlinePLUS

... 02 HRSA-15-133 Maternal and Child Health Public Health Catalyst Program Apply at Grants.gov by March ... website provides information about how EPSDT works with public health, families, managed care organizations, pediatricians, and other health ...

320

Maternal Depression and Adolescent Behavior  

MedlinePLUS

... hand corner of the player. Maternal Depression and Adolescent Behavior HealthDay December 22, 2014 Related MedlinePlus Pages ... depression, how does it impact her child in adolescence? A new study published in the journal Pediatrics ...

321

Assembly Bill 1825: Maternity Services  

E-print Network

infection Antepartum hemorrhage Placental abruption Preterm premature rupture of membranes Induction of labor Postpartuminfection*, maternity service*, medi-cal, neural tube defects, nuchal translucency, perinatal (care or service*), placenta previa, postnatal service*, postpartum

California Health Benefits Review Program (CHBRP)

2010-01-01

322

Neurotensin inversely modulates maternal aggression  

PubMed Central

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT’s role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 ?g). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 ?g) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 ?g), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 ?g NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. PMID:19118604

Gammie, Stephen C.; D’Anna, Kimberly L.; Gerstein, Hilary; Stevenson, Sharon A.

2008-01-01

323

Fetal programming by maternal obesity increases offspring’s susceptibility to obesity in later-life  

Technology Transfer Automated Retrieval System (TEKTRAN)

To examine whether exposure of the developing fetus to an obese mother during pregnancy increases the risk of obesity in the children in later-life, we have developed an overfeeding-based model of maternal obesity in rats by tube feeding of liquid diets directly into the stomach using total enteral ...

324

MATERNAL HYPOTHYROXENEMIA LEADS TO PERSISTENT DEFICITS IN HIPPOCAMPAL SYNAPTIC TRANSMISSION AND LEARNING IN OFFSPRING.  

EPA Science Inventory

MATERNAL HYPOTHYROXINEMIA LEADS TO PERSISTENT DEFICITS IN HIPPOCAMPAL SYNAPTIC TRANSMISSION AND LEARNING IN RAT OFFSPRING. M.E. Gilbert1 and Li Sui2, Neurotoxicology Division, 1US EPA and 2National Research Council, Research Triangle Pk, NC 27711. While severe hypothyroidis...

325

Natural Variations in Maternal Care Are Associated with Estrogen Receptor Expression and Estrogen  

E-print Network

/grooming (LG) over the first week postpartum. Such naturally occurring variations in maternal behavior are as- sociated with differences in estrogen-inducible oxytocin re- ceptors in the medial preoptic area (MPOA the offspring of Low LG mothers are Low LG moth- ers (4). In the rat, central oxytocin (OT) receptor levels

Champagne, Frances A.

326

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. PMID:21603074

Feng, Joyce Yen; Han, Wen-Jui

2011-01-01

327

Paradoxes of maternal mourning.  

PubMed

It has been customary to conceptualize mourning as a phasic or stage phenomenon (Lindemann 1944; Parkes 1972; Bowlby 1980; Knapp 1986). Such a conceptualization has proved to be of tremendous didactic value, especially in terms of succinctly organizing and communicating the major affects, behaviors, and reactions of mourning. It is, however, my belief, based upon clinical experience with many forms of bereavement, that the phenomenon of mourning is not comprised of clearly delineated stages and phases. I have come to conceptualize the phenomenon of mourning the death of a loved person as involving the bereaved's struggle with a series of more or less unresolvable paradoxes rather than as a progression through stages that possess relatively distinct and predictable beginning and ending points. The specific paradoxes encountered by a bereaved person differ, of course, in accordance with the relationship that was lost (mother, father, spouse, child, or sibling), the developmental stage of the bereaved (childhood, adolescence, adulthood, or maturity), the type of death (sudden or prolonged), and the cause of death (illness, murder, suicide, or accident). In this paper, I will address those paradoxes that seem specific to maternal mourning - that is, to mothers who are mourning the death of a child. PMID:2023970

Brice, C W

1991-02-01

328

Mild Diabetes Models and Their Maternal-Fetal Repercussions  

PubMed Central

The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue. PMID:23878822

Damasceno, D. C.; Sinzato, Y. K.; Bueno, A.; Netto, A. O.; Dallaqua, B.; Gallego, F. Q.; Iessi, I. L.; Corvino, S. B.; Serrano, R. G.; Marini, G.; Piculo, F.; Calderon, I. M. P.; Rudge, M. V. C.

2013-01-01

329

Maternal micronutrients and brain global methylation patterns in the offspring.  

PubMed

Objectives Studies have established the association of maternal nutrition and increased risk for non-communicable diseases. It has been suggested that this involves epigenetic modifications in the genome. However, the role of maternal micronutrients in the one-carbon cycle in influencing brain development of the offspring through methylation is unexplored. It is also unclear whether epigenomic marks established during early development can be reversed by a postnatal diet. The present study reports the effect of maternal micronutrients and omega-3 fatty acids on global DNA methylation patterns in the brain of the Wistar rat offspring at three timepoints (at birth, postnatal day 21, and 3 months of age). Method Pregnant rats were divided into control (n = 8) and five treatment groups (n = 16 dams in each group) at two levels of folic acid (normal and excess folate) in the presence and absence of vitamin B12 (NFBD, EFB, and EFBD). Omega-3 fatty acid supplementation was given to vitamin B12 deficient groups (NFBDO and EFBDO). Following delivery, eight dams from each group were shifted to control diet and remaining continued on the same treatment diet. Results Our results demonstrate that maternal micronutrient imbalance results in global hypomethylation in the offspring brain at birth. At adult age the cortex of the offspring displayed hypermethylation as compared with control, in spite of a postnatal control diet. In contrast, prenatal omega-3 fatty acid supplementation was able to normalize methylation at 3 months of age. Discussion Our findings provide clues for the role of omega-3 fatty acids in reversing methylation patterns thereby highlighting its contribution in neuroprotection and cognition. PMID:24257323

Sable, Pratiksha; Randhir, Karuna; Kale, Anvita; Chavan-Gautam, Preeti; Joshi, Sadhana

2015-01-01

330

Differential effect of maternal diet supplementation with ?-Linolenic acid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains  

Microsoft Academic Search

BACKGROUND: Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates. METHODS: Sprague-Dawley

Frédéric Destaillats; Corinne Joffre; Niyazi Acar; Florent Joffre; Jean-Baptiste Bezelgues; Bruno Pasquis; Cristina Cruz-Hernandez; Serge Rezzi; Ivan Montoliu; Fabiola Dionisi; Lionel Bretillon

2010-01-01

331

Developmental toxicity of brominated flame retardants, tetrabromobisphenol A and 1,2,5,6,9,10-hexabromocyclododecane, in rat offspring after maternal exposure from mid-gestation through lactation  

Microsoft Academic Search

To evaluate developmental exposure effects of two brominated flame retardants, tetrabromobisphenol A (TBBPA) and 1,2,5,6,9,10-hexabromocyclododecane (HBCD), pregnant Sprague–Dawley rats were administered either chemical at doses of 100, 1000 or 10,000ppm in a soy-free diet from gestation day 10 until the day 20 after delivery. Offspring exposed to TBBPA showed dose-unrelated slight decreases of serum triiodothyronine (T3) concentration at postnatal day

Yukie Saegusa; Hitoshi Fujimoto; Gye-Hyeong Woo; Kaoru Inoue; Miwa Takahashi; Kunitoshi Mitsumori; Masao Hirose; Akiyoshi Nishikawa; Makoto Shibutani

2009-01-01

332

Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats  

PubMed Central

This study isolated the effects of maternal hypoxia independent of changes in maternal nutrition on maternal circulatory and placental molecular indices of oxidative stress and determined whether maternal antioxidant treatment conferred protection. Pregnant rats were subjected to normoxic pregnancy or 13% O2 chronic hypoxia for most of gestation with and without maternal treatment with vitamin C in the drinking water. Maternal hypoxia with and without vitamin C did not affect maternal food or water intake and led to a significant increase in maternal and fetal haematocrit. At gestational day 20, maternal plasma urate and l-cysteine concentrations, and placental levels of 4-hydroxynonenal and heat shock protein 70 were increased while placental heat shock protein 90 levels were decreased in hypoxic pregnancy. The induction of maternal circulatory and placental molecular indices of oxidative stress in hypoxic pregnancies was prevented by maternal treatment with vitamin C. Maternal hypoxia during pregnancy with or without vitamin C increased placental weight, but not total or compartmental volumes. Maternal treatment with vitamin C increased birth weight in both hypoxic and normoxic pregnancies. The data show that maternal hypoxia independent of maternal undernutrition promotes maternal and placental indices of oxidative stress, effects that can be prevented by maternal treatment with vitamin C in hypoxic pregnancy. While vitamin C may not be the ideal candidate of choice for therapy in pregnant women, and taking into consideration differences in ascorbic acid metabolism between rats and humans, the data do underlie that antioxidant treatment may provide a useful intervention to improve placental function and protect fetal growth in pregnancy complicated by fetal hypoxia. PMID:22289909

Richter, H G; Camm, E J; Modi, B N; Naeem, F; Cross, C M; Cindrova-Davies, T; Spasic-Boskovic, O; Dunster, C; Mudway, I S; Kelly, F J; Burton, G J; Poston, L; Giussani, D A

2012-01-01

333

Maternal complications in diabetic pregnancy.  

PubMed

Pregnant women with diabetes have to manage both the effect of pregnancy on glucose control and its effect on pre-existing diabetic complications. Most women experience hypoglycaemia as a consequence of tightened glycaemic control and this impacts on daily living. Less commonly, diabetic ketoacidosis, a serious metabolic decompensation of diabetic control and a medical emergency, can cause foetal and maternal mortality. Microvascular complications of diabetes include retinopathy and nephropathy. Retinopathy can deteriorate during pregnancy; hence, regular routine examination is required and, if indicated, ophthalmological input. Diabetic nephropathy significantly increases the risk of obstetric complications and impacts on foetal outcomes. Pregnancy outcome is closely related to pre-pregnancy renal function. Diabetic pregnancy is contraindicated if the maternal complications of ischaemic heart disease or diabetic gastropathy are known to be present before pregnancy as there is a significant maternal mortality associated with both of these conditions. PMID:21130689

Hawthorne, Gillian

2011-02-01

334

Maternal low-protein diet alters the expression of real-time quantitative polymerase chain reaction reference genes in an age-, sex-, and organ-dependent manner in rat offspring.  

PubMed

Altered perinatal environment, often manifested as low birth weight, is thought to contribute to greater susceptibility for hypertension, hyperlipidemia, and diabetes as a result of epigenetic modifications and alteration of transcriptional activity for key genes. Real-time polymerase chain reaction is a useful technique for the quantitative determination of differences in transcriptional activity. Real-time quantitative polymerase chain reaction data analyses require normalization of transcriptional activity of target genes to an endogenous control, usually a reference gene. In response to reports of altered expression of reference genes in various experimental models, we hypothesized that adverse perinatal environment alters reference gene expression. We examined the expression of the following reference genes in the offspring of a rodent maternal low-protein diet model: ?-actin, hypoxanthine phosphoribosyltransferase 1, TATA-box-binding protein, glyceraldehyde-3-phosphate dehydrogenase, and glucuronidase-? in brain, heart, kidneys, and intestines. We found altered expression in brain, heart, and kidneys for each of the reference genes measured; these effects were age, organ, and sex dependent. Glyceraldehyde-3-phosphate dehydrogenase and glucuronidase-? were found to be the least affected by these variables, whereas hypoxanthine phosphoribosyltransferase 1 was the most inconsistent. Our findings underscore the importance of empirical determination of a reliable reference gene for real-time polymerase chain reaction studies in the low-protein diet model. PMID:23507230

DuBois, Barent; Pearson, Jacob; Hastings, Bonnie; Mahmood, Tahir; Chan, Tammy; Alnakhli, Ali; Cherala, Ganesh

2013-03-01

335

Postzygotic Maternal Influences and the Maternal-Embryonic Relationship of Viviparous Fishes  

Microsoft Academic Search

SYNOPSIS. Viviparous reproduction in fishes provides opportunities for maternal phenotypic modifications to influence offspring phenotype fol- lowing fertilization. Various physiological adaptations associated with the maintenance and control of prenatal embryonic development may provide the means by which postnatal phenotype is impacted by maternal phe- notype. It is widely recognized that postzygotic maternal influences may be mediated through the maternal-embryonic trophic

JULIAN LOMBARDI

1996-01-01

336

Web Sites Related to Maternal and Child Health Web Sites Related to Maternal and Child Health  

E-print Network

Web Sites Related to Maternal and Child Health Web Sites Related to Maternal and Child Health://www.aap.org Association of Maternal and Child Health Programs http://www.amchp1.org Center on Children & the Law http://www.abanet.org/child of Dimes Birth Defects Foundation http://www.modimes.org Maternal and Child Health Neighborhood http

de Lijser, Peter

337

Maternal immune transfer in mollusc.  

PubMed

Maternal immunity refers to the immunity transferred from mother to offspring via egg, playing an important role in protecting the offspring at early life stages and contributing a trans-generational effect on offspring's phenotype. Because fertilization is external in most of the molluscs, oocytes and early embryos are directly exposed to pathogens in the seawater, and thus maternal immunity could provide a better protection before full maturation of their immunological systems. Several innate immune factors including pattern recognition receptors (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide binding protein/bacterial permeability-increasing proteins (LBP/BPI) and antioxidant enzymes have been identified as maternally derived immune factors in mollusc eggs. Among these immune factors, some maternally derived lectins and antibacterial factors have been proved to endue mollusc eggs with effective defense ability against pathogen infection, while the roles of other factors still remain untested. The physiological condition of mollusc broodstock has a profound effect on their offspring fitness. Many other factors such as nutrients, pathogens, environment conditions and pollutants could exert considerable influence on the maternal transfer of immunity. The parent molluscs which have encountered an immune stimulation endow their offspring with a trans-generational immune capability to protect them against infections effectively. The knowledge on maternal transfer of immunity and the trans-generational immune effect could provide us with an ideal management strategy of mollusc broodstock to improve the immunity of offspring and to establish a disease-resistant family for a long-term improvement of cultured stocks. PMID:24858027

Wang, Lingling; Yue, Feng; Song, Xiaorui; Song, Linsheng

2015-02-01

338

Maternal programming of defensive responses through sustained effects on gene expression.  

PubMed

There are profound maternal effects on individual differences in defensive responses and reproductive strategies in species ranging literally from plants to insects to birds. Maternal effects commonly reflect the quality of the environment and are most likely mediated by the quality of the maternal provision (egg, propagule, etc.), which in turn determines growth rates and adult phenotype. In this paper we review data from the rat that suggest comparable forms of maternal effects on defensive responses stress, which are mediated by the effects of variations in maternal behavior on gene expression. Under conditions of environmental adversity maternal effects enhance the capacity for defensive responses in the offspring. In mammals, these effects appear to 'program' emotional, cognitive and endocrine systems towards increased sensitivity to adversity. In environments with an increased level of adversity, such effects can be considered adaptive, enhancing the probability of offspring survival to sexual maturity; the cost is that of an increased risk for multiple forms of pathology in later life. PMID:16513241

Zhang, Tie-Yuan; Bagot, Rose; Parent, Carine; Nesbitt, Cathy; Bredy, Timothy W; Caldji, Christian; Fish, Eric; Anisman, Hymie; Szyf, Moshe; Meaney, Michael J

2006-07-01

339

Early renal structure alteration in rat offspring from dams fed low protein diet.  

PubMed

To investigate the early renal alterations due to severe maternal protein restriction (MPR) Wistar dams received 23% (normal protein, NP) or 5% (low protein, LP) chow during gestation and lactation periods. In NP offspring at birth, the cortex-to-medulla (C/M) ratio was 35% greater in female than in male offspring and the mature/immature glomeruli ratio was lower in both sexes of LP offspring than in the matched NP ones (by 20%). At birth and at weaning the kidney of the LP offspring showed fewer glomeruli (40% less) than the age-matched NP offspring. The NP female offspring had almost 20% fewer glomeruli than the matched male offspring. At weaning, the number of glomeruli was positively correlated with BM at birth (R=0.86; P<0.001). The effects of gender and maternal protein restriction, both individually and overall, based on biometrical and stereological parameters were: day 1, MPR largely responsible for the majority of alterations observed in LP groups, however gender influenced C/M ratio; day 21, MPR and gender interacted and modified the number of glomeruli per kidney. The early adverse of MPR effect on renal development is disproportionate between mature and immature glomeruli at birth leading to fewer glomeruli at weaning. This supports epidemiological data in humans underlying why fetuses with low birth weight carry an increased risk of mortality from chronic diseases in adulthood, including hypertension. PMID:16890246

Pires, Karla Maria Pereira; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

2006-10-26

340

Gestational low protein diet selectively induces the amino acid response pathway target genes in the liver of offspring rats through transcription factor binding and histone modifications  

Microsoft Academic Search

The amino acid response (AAR) pathway detects a deficiency of dietary amino acid or protein. To investigate the impact of gestational protein restriction on the AAR pathway in offspring, pregnant Sprague–Dawley rats were fed a control (C) or low protein (LP) diet during gestation. Livers of female offspring were collected on postnatal d 38. The mRNA amount of Atf3 in

Dan Zhou; Yuan-Xiang Pan

2011-01-01

341

Plotting Maternity in Three Persons  

ERIC Educational Resources Information Center

This performance text examines complexities of personal and maternal identity in family life. Speaking in first, second, and third person voices, the author offers autoethnographic accounts of the tensions between separateness and connectedness, normative and subjective motherhood, and novice and seasoned perspectives. The piece functions as a…

Kinser, Amber E.

2012-01-01

342

Maternal depression and parenting behavior  

Microsoft Academic Search

The results of 46 observational studies were analyzed to assess the strength of the association between depression and parenting behavior and to identify variables that moderated the effects. The association between depression and parenting was manifest most strongly for negative maternal behavior and was evident to a somewhat lesser degree in disengagement from the child. The association between depression and

M. Christine Lovejoy; Patricia A Graczyk; Elizabeth O'Hare; George Neuman

2000-01-01

343

Maternal employment and adolescent development  

Microsoft Academic Search

This study investigates how maternal employment is related to the cognitive development and body weight of 10 and 11 year olds, controlling for a wide variety of child, mother and family characteristics. The results suggest that limited market work benefits youths who are relatively “disadvantaged” and even long hours, which occur infrequently, are unlikely to leave them much worse off. By

Christopher J. Ruhm

2008-01-01

344

Maternal age and duration of labor.  

PubMed

The computerized records of a population of 7214 women who were delivered during the period 1987-1991 were analysed. We studied the possible relationship of the duration of the first and second stages of labor to maternal age. In para 0, para 1 and para 2+ mothers we found an independent positive correlation between the second stage duration and maternal age. By multiple stepwise regression analysis maternal age turns out to be one of the most influential maternal characteristics of the second stage of labor. No correlation was found between maternal age and the duration of the first stage. PMID:8122504

Rasmussen, S; Bungum, L; Høie, K

1994-03-01

345

Links between maternal health and NCDs.  

PubMed

Non-communicable diseases (NCDs) and maternal health are closely linked. NCDs such as diabetes, obesity and hypertension have a significant adverse impact on maternal health and pregnancy outcomes, and through the mechanism of intrauterine programming maternal health impacts the burden of NCDs in future generations. The cycle of vulnerability to NCDs is repeated with increasing risk accumulation in subsequent generations. This article discusses the impact, interlinkages and advocates for integration of services for maternal and child health, NCD care and prevention and health promotion to sustainably improve maternal health as well address the rising burden of NCDs. PMID:25199858

Kapur, Anil

2015-01-01

346

Maternal Characteristics Predicting Young Girls’ Disruptive Behavior  

PubMed Central

Little is known about the relative predictive utility of maternal characteristics and parenting skills on the development of girls’ disruptive behavior. The current study used five waves of parent and child-report data from the ongoing Pittsburgh Girls Study to examine these relationships in a sample of 1,942 girls from age 7 to 12 years. Multivariate Generalized Estimating Equation (GEE) analyses indicated that European American race, mother’s prenatal nicotine use, maternal depression, maternal conduct problems prior to age 15, and low maternal warmth explained unique variance. Maladaptive parenting partly mediated the effects of maternal depression and maternal conduct problems. Both current and early maternal risk factors have an impact on young girls’ disruptive behavior, providing support for the timing and focus of the prevention of girls’ disruptive behavior. PMID:21391016

van der Molen, Elsa; Hipwell, Alison E.; Vermeiren, Robert; Loeber, Rolf

2011-01-01

347

Maternal characteristics predicting young girls' disruptive behavior.  

PubMed

Little is known about the relative predictive utility of maternal characteristics and parenting skills on the development of girls' disruptive behavior. The current study used five waves of parent- and child-report data from the ongoing Pittsburgh Girls Study to examine these relationships in a sample of 1,942 girls from age 7 to 12 years. Multivariate generalized estimating equation analyses indicated that European American race, mother's prenatal nicotine use, maternal depression, maternal conduct problems prior to age 15, and low maternal warmth explained unique variance. Maladaptive parenting partly mediated the effects of maternal depression and maternal conduct problems. Both current and early maternal risk factors have an impact on young girls' disruptive behavior, providing support for the timing and focus of the prevention of girls' disruptive behavior. PMID:21391016

van der Molen, Elsa; Hipwell, Alison E; Vermeiren, Robert; Loeber, Rolf

2011-01-01

348

The evolution of multivariate maternal effects.  

PubMed

There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations. PMID:24722346

Kuijper, Bram; Johnstone, Rufus A; Townley, Stuart

2014-04-01

349

Effect of Maternal Steroid on Developing Diaphragm Integrity  

PubMed Central

Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction. PMID:24681552

Song, Yong; Demmer, Denise L.; Pinniger, Gavin J.; Lavin, Tina; MacMillan, Mia V.; Pillow, Jane J.; Bakker, Anthony J.

2014-01-01

350

Effect of postnatal maternal protein intake on prenatal programming of hypertension.  

PubMed

This study examined whether postnatal maternal dietary protein deprivation during the time of nursing can program hypertension when the offspring are studied as adults. Rats were fed either a 6% or 20% protein diet during the second half of pregnancy and continued on the same diet while rats were nursing their pups. The neonates of all of the rats were cross-fostered to a different mother and studied as adults. Adult rats that had a normal prenatal environment but were reared by mothers fed a low-protein diet until weaning (20%-6%) were hypertensive, had a higher renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) and Na(+)-Cl(-) cotransporter (NCC) protein abundance yet a comparable number of glomeruli, and had higher plasma renin and angiotensin II levels compared to control (20%-20%). Rats whose mothers were fed a 6% protein diet and cross-fostered to a different rat fed a 6% protein diet until weaning (6%-6%) were hypertensive, had elevated plasma renin and angiotensin II levels, and had a reduction in nephron number but had NKCC2 and NCC levels comparable to 20% to 20% offspring. The 6% to 20% had blood pressure and glomerular numbers comparable to 20% to 20% rats. The hypertension resulting from prenatal dietary protein deprivation can be normalized by improving the postnatal environment. Combined prenatal and postnatal maternal dietary protein deprivation and maternal dietary protein deprivation while nursing alone (20%-6%) results in hypertension, but the mechanism for the hypertension in these groups is different. PMID:24740990

Siddique, Khurrum; Guzman, German Lozano; Gattineni, Jyothsna; Baum, Michel

2014-12-01

351

Media representation of maternal neonaticide  

E-print Network

delineating the charges, convictions, and sentences of all maternal infanticide cases in the United States over time. However, Wilczynski (1997) examined case files of child-killings by parents in London, and found that criminal justice systems respond... differently to men and women who have killed their children. Women were less likely than men to be prosecuted for or convicted of murder. In addition, women are more likely than men to use psychiatric pleas for their diminished responsibility and receive...

Lewis, Jocelyn Renee

2008-10-10

352

Maternal Methyl Donors Supplementation during Lactation Prevents the Hyperhomocysteinemia Induced by a High-Fat-Sucrose Intake by Dams  

PubMed Central

Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle. PMID:24351826

Cordero, Paul; Milagro, Fermin I.; Campion, Javier; Martinez, J. Alfredo

2013-01-01

353

The Effect of Maternal Nutrition on the Development of the Offspring: An International Symposium. Nutrition Reports International, Special Issue.  

ERIC Educational Resources Information Center

Contents of this symposium include the following papers: "Effect of Maternal Protein Malnutrition on Neonatal Lung Development and Mitochondrial Function," E. J. Hawrylewicz, J. Q. Kissane, W. H. Blair and C. A. Heppner; "Effect of the Level of Nutrition on Rates of Cell Proliferation and of RNA and Protein Syntheses in the Rat," L. M. Roeder;…

Roeder, Lois M., Ed.

1973-01-01

354

Maternal non-phenylketonuric mild hyperphenylalaninemia  

Microsoft Academic Search

Unlike maternal phenylketonuria (PKU) which produces severe birth defects when untreated during pregancy, maternal non-PKU\\u000a mild hyperphenylalaninemia (MHP) has a less severe impact but whether it is benign or may have long-term consequences for\\u000a offspring has been unclear. From an international survey of maternal MHP we obtained information about 86 mothers (blood phenylalanine\\u000a (Phe) 150–720 µmol\\/1), their 219 untreated pregnancies

H. L. Levy; S. E. Waisbren; D. Lobbregt; E. Allred; A. Leviton; R. Koch; W. B. Hanley; B. Rouse; R. Matalon; F. de la Cruz

1996-01-01

355

IFITM Proteins Restrict Viral Membrane Hemifusion  

E-print Network

In contrast, raising the temperature led to a significantfusion): Raising temperature led to calcein transfer to onlyled two target cells receiving calcein-AM, illustrating that fusion was as extensive upon addition of CPZ as upon raising temperature. (

2013-01-01

356

The Neuroendocrinology of Primate Maternal Behavior  

PubMed Central

In nonhuman primates and humans, similar to other mammals, hormones are not strictly necessary for the expression of maternal behavior, but nevertheless influence variation in maternal responsiveness and parental behavior both within and between individuals. A growing number of correlational and experimental studies have indicated that high circulating estrogen concentrations during pregnancy increase maternal motivation and responsiveness to infant stimuli, while effects of prepartum or postpartum estrogens and progestogens on maternal behavior are less clear. Prolactin is thought to play a role in promoting paternal and alloparental care in primates, but little is known about the relationship between this hormone and maternal behavior. High circulating cortisol levels appear to enhance arousal and responsiveness to infant stimuli in young, relatively inexperienced female primates, but interfere with the expression of maternal behavior in older and more experienced mothers. Among neuropeptides and neurotransmitters, preliminary evidence indicates that oxytocin and endogenous opioids affect maternal attachment to infants, including maintenance of contact, grooming, and responses to separation. Brain serotonin affects anxiety and impulsivity, which in turn may affect maternal behaviors such as infant retrieval or rejection of infants’ attempts to make contact with the mother. Although our understanding of the neuroendocrine correlates of primate maternal behavior has grown substantially in the last two decades, very little is known about the mechanisms underlying these effects, e.g., the extent to which these mechanisms may involve changes in perception, emotion, or cognition. PMID:20888383

Saltzman, Wendy; Maestripieri, Dario

2010-01-01

357

Maternal Psychiatric Disorders, Parenting, and Maternal Behavior in the Home during the Child Rearing Years  

ERIC Educational Resources Information Center

Data from the Children in the Community Study, a community-based longitudinal study, were used to investigate associations between maternal psychiatric disorders and child-rearing behaviors. Maternal psychiatric symptoms and behavior in the home were assessed in 782 families during the childhood and adolescence of the offspring. Maternal anxiety,…

Johnson, Jeffrey G.; Cohen, Patricia; Kasen, Stephanie; Brook, Judith S.

2006-01-01

358

Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats  

PubMed Central

During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics. PMID:25210695

Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

2014-01-01

359

A Dimensional Approach to Maternal Attachment State of Mind: Relations to Maternal Sensitivity and Maternal Autonomy Support  

ERIC Educational Resources Information Center

The aim of this study was to examine the developmental significance of the newly developed dimensional approach to attachment state of mind by investigating its capacity to predict individual differences in the quality of two caregiving behaviors--maternal sensitivity and maternal autonomy support--that are linked to numerous important child…

Whipple, Natasha; Bernier, Annie; Mageau, Genevieve A.

2011-01-01

360

Framing maternal morbidity: WHO scoping exercise  

PubMed Central

Background Maternal morbidity estimations are not based on well-documented methodologies and thus have limited validity for informing efforts to address the issue and improve maternal health. To fill this gap, maternal morbidity needs to be clearly defined, driving the development of tools and indicators to measure and monitor maternal health. This article describes the scoping exercise conducted by the World Health Organization’s Department of Reproductive of Health and Research (WHO/RHR), as an essential first step in this process. Methods A literature review was conducted to identify the range of definitions and conditions included in various studies of maternal morbidity with a special focus on the similarities and discrepancies of the definitions used across the studies. Furthermore a questionnaire was developed which included sections on key areas identified during the review and was sent out electronically to 130 international experts in the field of maternal health. Results Maternal morbidities have been categorized in a variety of ways based on the causes, types of complications, and/or timeline. Issues regarding the time frame, severity, identification and classification and demographics were identified as key areas in the literature that require further investigation to achieve consensus on a maternal morbidity definition. Fifty-five (N?=?55) individuals responded with completed questionnaires. Respondents’ views on the time frame for the postpartum period varied from 6 weeks to beyond one year postpartum, it was noted that time frame depended on the type of complication. The majority of respondents said maternal morbidity should comprise a continuum of severity, whereas the identification of the cases should use a mixed criteria employing multiple methods. Conclusions Significant discrepancy in literature and expert opinion exists concerning elements of a maternal morbidity definition. There is a clear need for a concrete definition that would allow for consistent measurement and monitoring of maternal morbidity across settings and time. PMID:24252359

2013-01-01

361

Understanding Global Trends in Maternal Mortality  

PubMed Central

CONTEXT Despite the fact that most maternal deaths are preventable, maternal mortality remains high in many developing countries. Target A of Millennium Development Goal (MDG) 5 calls for a three-quarters reduction in the maternal mortality ratio (MMR) between 1990 and 2015. METHODS We derived estimates of maternal mortality for 172 countries over the period 1990–2008. Trends in maternal mortality were estimated either directly from vital registration data or from a hierarchical or multilevel model, depending on the data available for a particular country. RESULTS The annual number of maternal deaths worldwide declined by 34% between 1990 and 2008, from approximately 546,000 to 358,000 deaths. The estimated MMR for the world as a whole also declined by 34% over this period, falling from 400 to 260 maternal deaths per 100,000 live births. Between 1990 and 2008, the majority of the global burden of maternal deaths shifted from Asia to Sub-Saharan Africa. Differential trends in fertility, the HIV/ AIDS epidemic and access to reproductive health are associated with the shift in the burden of maternal deaths from Asia to Sub-Saharan Africa. CONCLUSIONS Although the estimated annual rate of decline in the global MMR in 1990–2008 (2.3%) fell short of the level needed to meet the MDG 5 target, it was much faster than had been thought previously. Targeted efforts to improve access to quality maternal health care, as well as efforts to decrease unintended pregnancies through family planning, are necessary to further reduce the global burden of maternal mortality. PMID:23584466

Zureick-Brown, Sarah; Newby, Holly; Chou, Doris; Mizoguchi, Nobuko; Say, Lale; Suzuki, Emi; Wilmoth, John

2013-01-01

362

Maternal influences on birth weight.  

PubMed

The birth weight of 2,848 singleton babies delivered Al-Medina District hospitals was studied. The mean birth weight of Al-Medina babies was 3.26 Kg. (SD 0.44), the males with mean birth weight of 3.32 Kg. (SD 0.45), and were significantly heavier than females with a mean birth weight of 3.20 Kg. (SD 0.42). The incidence of low birth weight was 7.0 per cent. The birth weight was found to increase consistently with maternal age, parity, and height. Birth weight was significantly higher for babies of non-consanguineous parents. PMID:2500524

al-Sekait, M A

1989-04-01

363

Maternal depressive symptoms, maternal behavior, and toddler internalizing outcomes: a moderated mediation model.  

PubMed

Maternal depression relates to child internalizing outcomes, but one missing aspect of this association is how variation in depressive symptoms, including mild and moderate symptoms, relates to young children's outcomes. The current study examined a moderated mediation model to investigate how maternal behaviors may mediate this association in the context of child temperament and gender. Mothers and toddlers completed a free-play/clean-up task in the laboratory. Mothers rated their depressive symptoms and their toddlers' temperament and internalizing behaviors. Results indicated a significant indirect effect of maternal warmth on the relation between maternal depressive symptoms and toddler internalizing outcomes for boys with low negative emotionality. Toddler gender and temperament moderated the relation between maternal intrusiveness and toddler internalizing outcomes, but mediation was not supported. Results highlight the important interaction between child and maternal variables in predicting child outcomes, and suggest mechanisms by and conditions under which mild maternal depressive symptomatology can be a risk factor for toddler internalizing outcomes. PMID:24553739

Hummel, Alexandra C; Kiel, Elizabeth J

2015-02-01

364

NEW RESEARCH Maternal Early Life Experiences and  

E-print Network

support for the notion that mediators linking early life experiences to parenting in humans may be similar experiences to maternal sensitivity. Early Experience and Parenting in Humans There is much evidence explanations have largely been overlooked. Early Experience and Maternal Behavior in Non- Human Animals Studies

Sokolowski, Marla

365

NATIONAL MATERNAL AND INFANT HEALTH SURVEY (NMIHS)  

EPA Science Inventory

The National Maternal and Infant Health Survey (NMIHS) provides data on maternal and infant health, including prenatal care, birth weight, fetal loss, and infant mortality. The objective of the NMIHS is to collect data needed by Federal, State, and private researchers to study fa...

366

Autism Symptom Topography and Maternal Socioemotional Functioning  

ERIC Educational Resources Information Center

Researchers examining the relationship of autism "symptomatology" and maternal stress have defined symptomatology in terms of level of severity, frequency of occurrence, or symptom type. In the present study, the relationship of maternal perceptions of these dimensions, along with a fourth, symptom diversity, and negative and positive indices of…

Ekas, Naomi; Whitman, Thomas L.

2010-01-01

367

Maternal Labor Supply and Children's Cognitive Development  

Microsoft Academic Search

This paper analyzes the relationship between maternal labor supply and children's cognitive development using a sample of three- and four-year-old children of female respondents from the 1986 National Longitudinal Survey Youth Cohort. Maternal employment is found to have a negative impact when it occurs during the first year of the child's life and a potentially offsetting positive effect when it

Francine D Blau; Adam J Grossberg

1992-01-01

368

Infant Communicative Behaviors and Maternal Responsiveness  

ERIC Educational Resources Information Center

Background: This study applies attachment and transactional theories in evaluating the dyadic interactions observed between a mother and her infant. Infant communication and maternal responsivity are highlighted as the medium for positive interaction. Objective: The impact of individualized maternal training on mother infant communicative…

DiCarlo, Cynthia F.; Onwujuba, Chinwe; Baumgartner, Jennifer I.

2014-01-01

369

Maternal Depression and Childhood Health Inequalities  

ERIC Educational Resources Information Center

An increasing body of literature documents considerable inequalities in the health of young children in the United States, though maternal depression is one important, yet often overlooked, determinant of children's health. In this article, the author uses data from the Fragile Families and Child Wellbeing Study (N = 4,048) and finds that maternal

Turney, Kristin

2011-01-01

370

Maternal Inattention and Impulsivity and Parenting Behaviors  

ERIC Educational Resources Information Center

This study extends previous research by examining whether maternal inattention, impulsivity, and hyperactivity are associated with different parenting behaviors. Ninety-six mother-son dyads participated in the study, and the boys ranged between 4 and 8 years of age. Maternal inattention was uniquely and positively associated with mothers' use of…

Chen, Mandy; Johnston, Charlotte

2007-01-01

371

Pharmacogenomics of Maternal Tobacco Use  

PubMed Central

OBJECTIVE To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke. METHODS DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption. RESULTS No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age–adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar. CONCLUSION Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age–corrected birth weight. PMID:20177288

Aagaard-Tillery, Kjersti; Spong, Catherine Y.; Thom, Elizabeth; Sibai, Baha; Wendel, George; Wenstrom, Katharine; Samuels, Philip; Simhan, Hyagriv; Sorokin, Yoram; Miodovnik, Menachem; Meis, Paul; O’Sullivan, Mary J.; Conway, Deborah; Wapner, Ronald J.

2011-01-01

372

Maternal Personality: Longitudinal Associations to Parenting Behavior and Maternal Emotional Expressions toward Toddlers.  

PubMed

OBJECTIVE: Longitudinal associations among maternal personality, emotional expressions, and parenting were examined. DESIGN: Maternal parenting (sensitivity and intrusiveness) and positive emotional expressions were observed during a free-play session with toddlers at 18 (T1, n = 246) and 30 (T3, n = 216) months. Mothers completed a personality measure at T1 and a questionnaire measuring their emotional expressiveness (positive and negative) when toddlers were 24 months old (T2, n = 213). RESULTS: Dimensions of maternal personality and maternal emotional expressiveness were related to individual differences in maternal parenting behaviors, in particular to maternal sensitivity. Conscientiousness and Agreeableness at T1 were positively associated with observed positive emotional expressions at T1. Agreeableness, Openness to Experience, and Extraversion at T1 also were positively related to positive emotional expressions reported by mothers at T2. Maternal positive emotional expressions (T1 and T2), in turn, were associated with more sensitive behavior observed with toddlers at T3. CONCLUSION: In addition to direct effects of maternal personality on maternal parenting, mothers' emotional expressiveness was found to be a possible pathway for explaining relations of maternal personality and parenting. PMID:18174914

Smith, Cynthia L; Spinrad, Tracy L; Eisenberg, Nancy; Gaertner, Bridget M; Popp, Tierney K; Maxon, Elizabeth

2007-01-01

373

How do Maternal PTSD and Alexithymia Interact to Impact Maternal Behavior?  

PubMed

Maternal interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) is known to be associated with impairment of a mother's capacity to participate in mutual emotion regulation during her child's first years of life. This study tested the hypothesis that maternal difficulty in identifying feelings in self and other, as an important dimension of the construct of alexithymia, together with maternal IPV-PTSD, would be negatively associated with maternal sensitivity. Maternal sensitivity to child emotional communication is a marker of maternal capacity to engage in mutual regulation of emotion and arousal. Following diagnostic interviews and administration of the Toronto Alexithymia Scale, 56 mothers and their toddlers (ages 12-42 months) were filmed during free-play and separation/novelty-exposure. Observed maternal sensitivity was coded via the CARE-Index. Maternal IPV-PTSD severity, difficulty in identifying emotions, and lower socio-economic status were all associated with less maternal sensitivity, and also with more maternal controlling and unresponsive behavior on the CARE-Index. PMID:25008189

Schechter, Daniel S; Suardi, Francesca; Manini, Aurelia; Cordero, Maria Isabel; Rossignol, Ana Sancho; Merminod, Gaëlle; Gex-Fabry, Marianne; Moser, Dominik A; Serpa, Sandra Rusconi

2014-07-10

374

Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring  

PubMed Central

Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24?h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased risk for stress-related pathology. PMID:25071719

Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

2014-01-01

375

Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment.  

PubMed

Throughout the lifespan, the brain has a considerable degree of plasticity and can be strongly influenced by sensory input from the outside environment. Given the importance of the environment in the regulation of the brain structure, behavior and physiology, the aim of the present work was to analyze the effects of different environmental qualities during two critical ontogenic periods (early life and peripuberty) on behavior and hippocampal physiology. Male Wistar rats were separated from their mothers for 4.5h daily during the first 3 weeks of life. They were weaned on day 21 and housed under either standard or enriched conditions. At 60 d of age, all animals were then housed in same-treatment groups, two per cage, until testing began on day 74. Emotional and cognitive responses were tested using the open field, novel object recognition test and step-down inhibitory avoidance learning. In the dorsal hippocampus, glucocorticoid receptor expression and neuronal activity were examined by immunoreactivity. Grooming behavior in the open field was found to be significantly lower in maternally separated animals, but post-weaning environmental enrichment completely reversed this tendency. Inhibitory avoidance but not object recognition memory was impaired in maternally separated animals, suggesting that early maternal separation alters learning and memory in a task-specific manner. Again, environmental enrichment reversed the effects of maternal separation on the inhibitory avoidance task. Even though maternal separation did not significantly affect Fos and glucocorticoid receptor (GR) expression, environmental enrichment increased both Fos expression in the total hippocampal area and also the overall number of GR positive cells per hippocampal area, mainly due to the changes in CA1. These findings suggest that differential rearing is a useful procedure to study behavioral and physiological plasticity in response to early experience and that, although the effects of adverse experience early in life such as maternal separation can persist until adulthood, some of them can be compensated by early favorable environments, possibly through nervous system plasticity. PMID:23195113

Vivinetto, Ana Laura; Suárez, Marta Magdalena; Rivarola, María Angélica

2013-03-01

376

Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting.  

PubMed

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development. PMID:25600754

Gannon, Matthew A; Brown, Clifford J; Stevens, Rachel M; Griffith, Molly S; Marczinski, Cecile A; Bardgett, Mark E

2015-03-01

377

Maternal vasoactive intestinal peptide and the regulation of embryonic growth in the rodent.  

PubMed Central

Vasoactive intestinal peptide (VIP) has been shown to regulate early postimplantation growth in rodents through central nervous system receptors. However, the source of VIP mediating these effects is unknown. Although VIP binding sites are present prenatally, VIP mRNA was not detected in the rat central nervous system before birth and was detected in the periphery only during the last third of pregnancy. In the present study, the embryonic day (E11) rat embryo/trophoblast was shown to have four times the VIP concentration of the E17 fetus and to have VIP receptors in the central nervous system. However, no VIP mRNA was detected in the E11 rat embryo or embryonic membranes by in situ hybridization or reverse transcriptase-PCR. RIA of rat maternal serum revealed a peak in VIP concentration at days E10-E12 of pregnancy, with VIP rising to levels 6-10-fold higher than during the final third of pregnancy. After intravenous administration of radiolabeled VIP to pregnant female mice, undegraded VIP was found in the E10 embryo. These results suggest that maternal tissues may provide neuroendocrine support for embryonic growth through a surge of VIP during early postimplantation development in the rodent. PMID:8550835

Hill, J M; McCune, S K; Alvero, R J; Glazner, G W; Henins, K A; Stanziale, S F; Keimowitz, J R; Brenneman, D E

1996-01-01

378

A model for maternal depression.  

PubMed

With the awareness of maternal depression as a prevalent public health issue and its important link to child physical and mental health, attention has turned to how healthcare providers can respond effectively. Intimate partner violence (IPV) and the use of alcohol, tobacco, and other drugs are strongly related to depression, particularly for low-income women. The American College of Obstetricians and Gynecologists (ACOG) recommends psychosocial screening of pregnant women at least once per trimester, yet screening is uncommonly done. Research suggests that a collaborative care approach improves identification, outcomes, and cost-effectiveness of care. This article presents The Perinatal Mental Health Model, a community-based model that developed screening and referral partnerships for use in community obstetric settings in order to specifically address the psychosocial needs of culturally diverse, low-income mothers. PMID:20718624

Connelly, Cynthia D; Baker-Ericzen, Mary J; Hazen, Andrea L; Landsverk, John; Horwitz, Sarah McCue

2010-09-01

379

Effects of maternal L-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: the impact of nitric oxide pathway.  

PubMed

Maternal undernutrition can cause reduced nephron number and glomerular hypertrophy, consequently leading to adult kidney disease. We intended to elucidate whether NO deficiency evolves to kidney disease vulnerability in offspring from mothers with caloric restriction diets and whether maternal L-citrulline (L-Cit) supplementation can prevent this. Using a rat model with 50% caloric restriction, four groups of 3-month-old male offspring were sacrificed to determine their renal outcome: control, caloric restriction (CR), control treated with 0.25% L-citrulline solution during the whole period of pregnancy and lactation (Cit), and CR treated in the same way (CR+Cit group). The CR group had low nephron numbers, increased glomerular diameter, and an increased plasma creatinine level compared with the control group. Maternal L-Cit supplementation prevented these effects. The CR+Cit and Cit groups developed hypertension beginning at 4 and 8weeks of age, respectively. Plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels were increased, but L-arginine/ADMA ratios (AAR) were decreased in the CR group vs the control group. This was prevented by maternal L-Cit supplementation. Renal cortical neuronal NOS-alpha (nNOSalpha) protein abundance was significantly decreased in the Cit and CR+Cit groups. Collectively, reduced nephron number, reduced renal nNOSalpha expression, increased ADMA, and decreased AAR contribute to the developmental programming of adult kidney disease and hypertension. Although maternal L-Cit supplementation prevents caloric restriction-induced low nephron number and renal dysfunction, it also induces hypertension. PMID:20371384

Tain, You-Lin; Hsieh, Chih-Sung; Lin, I-Chun; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Huang, Li-Tung

2010-08-01

380

Nutritional Recovery Promotes Hypothalamic Inflammation in Rats during Adulthood  

PubMed Central

We evaluated whether protein restriction in fetal life alters food intake and glucose homeostasis in adulthood by interfering with insulin signal transduction through proinflammatory mechanisms in the hypothalamus and peripheral tissues. Rats were divided into the following: a control group (C); a recovered group (R); and a low protein (LP) group. Relative food intake was greater and serum leptin was diminished in LP and R compared to C rats. Proinflammatory genes and POMC mRNA were upregulated in the hypothalamus of R group. Hypothalamic NPY mRNA expression was greater but AKT phosphorylation was diminished in the LP than in the C rats. In muscle, AKT phosphorylation was higher in restricted than in control animals. The HOMA-IR was decreased in R and C compared to the LP group. In contrast, the Kitt in R was similar to that in C and both were lower than LP rats. Thus, nutritional recovery did not alter glucose homeostasis but produced middle hyperphagia, possibly due to increased anorexigenic neuropeptide expression that counteracted the hypothalamic inflammatory process. In long term protein deprived rats, hyperphagia most likely resulted from increased orexigenic neuropeptide expression, and glucose homeostasis was maintained, at least in part, at the expense of increased muscle insulin sensitivity. PMID:25258479

Silva, Hellen Barbosa Farias; de Almeida, Ana Paula Carli; Cardoso, Katarine Barbosa; Ignacio-Souza, Letícia Martins; Reis, Silvia Regina de Lima; Reis, Marise Auxiliadora de Barros; Milanski, Marciane; Arantes, Vanessa Cristina

2014-01-01

381

Predicting Maternal Rat and Pup Exposures: How Different Are They?  

EPA Science Inventory

Risk and safety assessments for early life exposures to environmental chemicals or pharmaceuticals based on cross-species extrapolation would greatly benefit from information on chemical dosimetry in the young. Although relevant toxicity studies involve exposures during multiple ...

382

Maternal Hyperthyroidism in Rats Impairs Stress Coping of Adult Offspring  

E-print Network

. Herna´ndez,1 Mauricio Medina-Pizarro,1 Pablo Valle-Leija,1 Arturo Vega-Gonza´lez,1 and Teresa Morales2 1; Morreale de Escobar et al., 1988) and human (Vulsma et al., 1989) and are postulated to regulate fetal

Islas, León

383

Maternal dietary tryptophan deficiency alters cardiorespiratory control in rat pups  

PubMed Central

Malnutrition during pregnancy adversely affects postnatal forebrain development; its effect upon brain stem development is less certain. To evaluate the role of tryptophan [critical for serotonin (5-HT) synthesis] on brain stem 5-HT and the development of cardiorespiratory function, we fed dams a diet ?45% deficient in tryptophan during gestation and early postnatal life and studied cardiorespiratory variables in the developing pups. Deficient pups were of normal weight at postnatal day (P)5 but weighed less than control pups at P15 and P25 (P < 0.001) and had lower body temperatures at P15 (P < 0.001) and P25 (P < 0.05; females only). Oxygen consumption (V?o2) was unaffected. At P15, deficient pups had an altered breathing pattern and slower heart rates. At P25, they had significantly lower ventilation (V?e) and V?e-to-V?o2 ratios in both air and 7% CO2. The ventilatory response to CO2 (% increase in V?e/V?o2) was significantly increased at P5 (males) and reduced at P15 and P25 (males and females). Deficient pups had 41–56% less medullary 5-HT (P < 0.01) compared with control pups, without a difference in 5-HT neuronal number. These data indicate important interactions between nutrition, brain stem physiology, and age that are potentially relevant to understanding 5-HT deficiency in the sudden infant death syndrome. PMID:20966190

Penatti, Eliana M.; Barina, Alexis E.; Raju, Sharat; Li, Aihua; Kinney, Hannah C.; Commons, Kathryn G.

2011-01-01

384

Maternal undernutrition and the offspring kidney: from fetal to adult life.  

PubMed

Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1(R)) or type 2 (AT2(R)) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1(R) is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2(R) expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na(+)/K(+)-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na(+)/K(+)-ATPase, leading to increased Na(+) reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death. PMID:21049242

Mesquita, F F; Gontijo, J A R; Boer, P A

2010-11-01

385

Retardation of fetal brain cell growth during maternal starvation: circulating factors versus altered cellular response.  

PubMed

Maternal starvation inhibits fetal brain development during late gestation in the rat. To determine whether intrinsic or extrinsic factors might be the principal contributor to altered growth, brain cells from 20 day fetuses were cultured in a 96 well plate with MEM and 10% adult rat serum. Tissue growth was monitored by spectrophotometric measurement of the mitochondrial reduction of a chromagen 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT). After 1, 4 or 6 days incubation, MTT activity in non confluent cultures was shown to be directly related to tissue mass. When fetal brain cell cultures were incubated with 1% and 10% concentrations of adult rat serum, an 11-fold increase in MTT activity paralleled a 15-fold increase in tritiated thymidine incorporation. The impact of maternal starvation on fetal brain cell growth was examined by measuring MTT activity in fetal brain cells from fed and starved mothers. When cultures were incubated for 6 days with graded concentrations of fed adult serum (1.25-10%), the MTT response was slightly but consistently lower in cells from starved when compared with cells from fed mothers. By contrast, a marked difference in MTT activity which was paralleled by a lower DNA content became apparent when fetal rat brain cells were incubated with starved adult serum. Fetal serum and adult male serum were found to support growth equally well, while incubation of fetal brain cells with maternal sera resulted in lower MTT values than with the corresponding fetal sera. When cells were incubated with fetal sera pooled from starved mothers, MTT activity was decreased by 42 to 45%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1603259

Gu, D S; Shambaugh, G E; Metzger, B E; Unterman, T G; Radosevich, J A

1992-06-01

386

Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report: Part 2, Appendices  

SciTech Connect

Lewisite was administered to rats and rabbits by intragastric intubation. Maternal animals were weighed periodically, and, at necropsy (20 dg (days of gestation) in rats and 30 dg in rabbits), were examined for gross lesions of major organs and reproductive performances; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, a dose level of 1.5 mg/kg did not induce toxic or teratogenic responses in maternal animals or their fetuses. At 2.0 mg/kg, 10% maternal mortality, trends in decreased maternal and fetal body weights and a significant reduction in the number of viable fetuses were evident. In rabbit studies, maternal mortality occured in all but one of the lewisite treatment groups and range from 13% to 100% at dose levels of 0.07 and 1.5 mg/kg, respectively. This mortality rate limited the sample size and impaired the detection of statistical significance among treatments. However, at the lowest dose level of the teratology study (0.07 mg/kg), maternal mortality was the only indicator of lewisite toxicity; at the highest dose (0.6 mg/kg), significant findings included 86% maternal mortality, a decrease in maternal body weight gains and an increase in the incidence of fetal stunting, although only a tendency in decreased fetal body weights was observed. These results suggest that maternal mortality was the most important factor in predicting the induction of maternal and fetal effects and, therefore, a ''no observable effect level'' in maternal animals and their fetuses would be between 1.5 and 2.0 mg/kg in rats and less than 0.07 mg/kg in rabbits. Part 2 contains 6 appendices.

Hackett, P.L.; Sasser, L.B.; Rommereim, R.L.; Cushing, J.A.; Buschbom, R.L.; Kalkwarf, D.R.

1987-12-31

387

Epigenetic programming by maternal behavior  

Microsoft Academic Search

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged

Ian C G Weaver; Nadia Cervoni; Frances A Champagne; Ana C D'Alessio; Shakti Sharma; Jonathan R Seckl; Sergiy Dymov; Moshe Szyf; Michael J Meaney

2004-01-01

388

Maternal infection and white matter toxicity  

PubMed Central

Studies examining maternal infection as a risk factor for neurological disorders in the offspring have suggested that altered maternal immune status during pregnancy can be considered as an adverse event in prenatal development. Infection occurring in the mother during the gestational period has been implicated in multiple neurological effects. The current manuscript will consider the issue of immune/inflammatory conditions during prenatal development where adverse outcomes have been linked to maternal systemic infection. The discussions will focus primary on white matter and oligodendrocytes as they have been identified as target processes. This white matter damage occurs in very early preterm infants and in various other human diseases currently being examined for a linkage to maternal or early developmental immune status. The intent is to draw attention to the impact of altered immune status during pregnancy on the offspring for the consideration of such contributing factors to the general assessment of developmental neurotoxicology. PMID:16787664

Harry, G. Jean; Lawler, Cindy; Brunssen, Susan H.

2006-01-01

389

Maternal and Child Health Leadership Competencies  

E-print Network

Maternal and Child Health Leadership Competencies V E R S I O N 3 . 0 MCH Leadership Competencies? .................................................................................................. 2 Use of the MCH Leadership Competencies ................................................................... 2 Rationale for Development of MCH Leadership Competencies

Thomas, Andrew

390

Maternal immunization: opportunities for scientific advancement.  

PubMed

Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization. PMID:25425719

Beigi, Richard H; Fortner, Kimberly B; Munoz, Flor M; Roberts, Jeff; Gordon, Jennifer L; Han, Htay Htay; Glenn, Greg; Dormitzer, Philip R; Gu, Xing Xing; Read, Jennifer S; Edwards, Kathryn; Patel, Shital M; Swamy, Geeta K

2014-12-15

391

A strategy for reducing maternal mortality.  

PubMed Central

A confidential system of enquiry into maternal mortality was introduced in Malaysia in 1991. The methods used and the findings obtained up to 1994 are reported below and an outline is given of the resulting recommendations and actions. PMID:10083722

Suleiman, A. B.; Mathews, A.; Jegasothy, R.; Ali, R.; Kandiah, N.

1999-01-01

392

Pediatric, Adolescent, and Maternal AIDS Branch  

E-print Network

Institutes of Health National Institute of Child Health and Human Development #12;The informationPediatric, Adolescent, and Maternal AIDS Branch NICHD Adult Prevalence Rates HIV Infection ........................................................................................................................1 BACKGROUND: THE CONTINUED IMPACT OF HIV ON CHILDREN, ADOLESCENTS, AND WOMEN

Rau, Don C.

393

Maternal and child health in China.  

PubMed Central

China has made great progress in improving the health of women and children over the past two generations. The success has been attributed to improved living standards, public health measures, and good access to health services. Although overall infant and maternal mortality rates are relatively low there are large differences in patterns of mortality between urban and rural areas. The Chinese have developed a hierarchical network of maternal and child health services, with each level taking a supervisory and teaching role for the level below it. Matern