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


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

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



Maternal Protein Restriction Reduces Angiotensin II AT1 and AT2 Receptor Expression in the Fetal Rat Kidney  

Microsoft Academic Search

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 AT1 and AT2 receptor subtypes.

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



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


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



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


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

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



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


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



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

PubMed Central

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 volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. Methods Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. Results As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance. Conclusion Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.



Adolescent hyperactivity of offspring after maternal protein restriction during the second half of gestation and lactation periods in rats.  


To clarify the effect of systemic growth retardation on behavior, pregnant rats were fed a synthetic diet with either a normal (20% casein) or low (10% casein) protein concentration from gestational day 10 to postnatal day (PND) 21 at weaning. Offspring were examined for sensory and reflex functions, detailed clinical observations, manipulative test, grip strength, motor activity and water-filled multiple T-maze test. Lowering trend in the air righting reflex index during lactation period and a decrease in grip strength on PND 72 were observed in the low protein diet group showing suppression of systemic growth. However, they were simply the reflection of delayed systemic growth, because parameters on impaired reflex function, disturbance of motor function and paralysis were unaffected. On the other hand, low protein diet resulted in increased motor activity in female offspring. Thus, malnutrition due to maternal protein restriction may cause adolescent hyperactivity. PMID:22467025

Ohishi, Takumi; Wang, Liyun; Akane, Hirotoshi; Shiraki, Ayako; Sato, Akira; Uematsu, Masanobu; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto



Maternal protein restriction regulates IGF2 system in placental labyrinth.  


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



Maternal protein restriction leads to enhanced hepatic gluconeogenic gene expression in adult male rat offspring due to impaired expression of the liver X receptor.  


Epidemiological studies demonstrate that the link between impaired fetal development and glucose intolerance in later life is exacerbated by postnatal catch-up growth. Maternal protein restriction (MPR) during pregnancy and lactation in the rat has been previously demonstrated to lead to impaired glucose tolerance in adulthood, however the effects of protein restoration during weaning on glucose homeostasis are largely unknown. Recent in vitro studies have identified that the liver X receptor ? (LXR?) maintains glucose homeostasis by inhibiting critical genes involved in gluconeogenesis including G6pase (G6pc), 11?-Hsd1 (Hsd11b1) and Pepck (Pck1). Therefore, we hypothesized that MPR with postnatal catch-up growth would impair LXR? in vivo, which in turn would lead to augmented gluconeogenic LXR?-target gene expression and glucose intolerance. To examine this hypothesis, pregnant Wistar rats were fed a control (20%) protein diet (C) or a low (8%) protein diet during pregnancy and switched to a control diet at birth (LP). At 4 months, the LP offspring had impaired glucose tolerance. In addition, LP offspring had decreased LXR? expression, while hepatic expression of 11?-HSD1 and G6Pase was significantly higher. This was concomitant with decreased binding of LXR? to the putative LXRE on 11?-Hsd1 and G6pase. Finally, we demonstrated that the acetylation of histone H3 (K9,14) surrounding the transcriptional start site of hepatic Lxr? (Nr1h3) was decreased in LP offspring, suggesting MPR-induced epigenetic silencing of the Lxr? promoter. In summary, our study demonstrates for the first time the important role of LXR? in mediating enhanced hepatic gluconeogenic gene expression and consequent glucose intolerance in adult MPR offspring. PMID:23633563

Vo, Thin Xuan; Revesz, Andrew; Sohi, Gurjeev; Ma, Noelle; Hardy, Daniel B



Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7alpha-hydroxylase promoter.  


Adverse events in utero, such as intrauterine growth restriction (IUGR), can permanently alter epigenetic mechanisms leading to the metabolic syndrome, which encompasses a variety of symptoms including augmented cholesterol. The major site for cholesterol homeostasis occurs via the actions of hepatic cholesterol 7?-hydroxylase (Cyp7a1), which catabolizes cholesterol to bile acids. To determine whether posttranslational histone modifications influence the long-term expression of Cyp7a1 in IUGR, we used a protein restriction model in rats. This diet during pregnancy and lactation led to IUGR offspring with decreased liver to body weight ratios, followed by increased circulating and hepatic cholesterol levels in both sexes at d 21 and exclusively in the male offspring at d 130. The augmented cholesterol was associated with decreases in the expression of Cyp7a1. Chromatin immunoprecipitation revealed that this was concomitant with diminished acetylation and enhanced methylation of histone H3 lysine 9 [K9,14], markers of chromatin silencing, surrounding the promoter region of Cyp7a1. These epigenetic modifications originate in part due to dietary-induced decreases in fetal hepatic Jmjd2a expression, a histone H3 [K9] demethylase. Collectively, these findings suggest that the augmented cholesterol observed in low-protein diet-derived offspring is due to permanent repressive posttranslational histone modifications at the promoter of Cyp7a1. Moreover, this is the first study to demonstrate that maternal undernutrition leads to long-term cholesterol dysregulation in the offspring via epigenetic mechanisms. PMID:21372147

Sohi, Gurjeev; Marchand, Kelly; Revesz, Andrew; Arany, Edith; Hardy, Daniel B



Gestational protein restriction increases angiotensin II production in rat lung.  


Gestational protein restriction (PR) alters the renin-angiotensin system in uterine arteries and placentas and elevates plasma levels of angiotensin II in pregnant rats. To date, how PR increases maternal plasma levels of angiotensin II remains unknown. In this study, we hypothesize that the expression and/or the activity of angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) in lungs, but not kidneys and blood, largely contribute to elevated plasma angiotensin II levels in pregnant rats subject to gestational PR. Time-scheduled pregnant Sprague-Dawley rats were fed a normal or low-protein diet from Day 3 of pregnancy until euthanized at Day 19 or 22. Expressions of Ace and Ace2 (angiotens in I converting enzyme [peptidyl-dipeptidase A] 2) in lungs and kidneys from pregnant rats by quantitative real-time PCR and Western blotting, and the activities of these proteins in lungs, kidneys, and plasma, were measured. The mRNA levels of Ace and Ace2 in lungs were elevated by PR at both Days 19 and 22 of pregnancy. The abundance of ACE protein in lungs was increased, but ACE2 protein was decreased, by PR. The activities of ACE, but not ACE2, in lungs were increased by PR. PR did not change expressions of Ace and Ace2, the activities of both ACE and ACE2 in kidneys, and the abundance and activity of plasma ACE. These findings suggest that maternal lungs contribute to the elevated plasma levels of angiotensin II by increasing both the expression and the activity of ACE in response to gestational PR. PMID:23365412

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra



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

PubMed Central

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

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



Proteomic analysis of the maternal protein restriction rat model for schizophrenia: identification of translational changes in hormonal signaling pathways and glutamate neurotransmission.  


Previous studies have found that some first onset schizophrenia patients show signs of impaired insulin signaling. Also, epidemiological studies have shown that periods of suboptimal nutrition including protein deficiencies during pregnancy can lead to increased incidence of metabolic conditions and psychiatric disorders in the offspring. For these reasons, we have carried out a molecular profiling analysis of blood serum and brain tissues from adult offspring produced by the maternal low protein (LP) rat model. The results showed similar changes to those seen in schizophrenia. Multiplex immunoassay profiling identified changes in the levels of insulin, adiponectin, and leptin along with alterations in inflammatory and vascular system-related proteins such as osteopontin, macrophage colony-stimulating factor 1, and vascular cell adhesion molecule 1. LC-MS(E) proteomic profiling showed that glutamatergic pathways were altered in frontal cortex, while signaling pathways and cytoskeletal proteins involved in hormonal secretion and synaptic remodeling were altered in the hypothalamus. Taken together, these studies indicate that the LP rat model recapitulates several pathophysiological attributes seen in schizophrenia patients. We propose that the LP model may have utility for drug discovery efforts, especially to identify compounds that modulate the metabolic and glutamatergic systems. PMID:23071080

Guest, Paul C; Urday, Sebastian; Ma, Dan; Stelzhammer, Viktoria; Harris, Laura W; Amess, Bob; Pietsch, Sandra; Oheim, Christin; Ozanne, Susan E; Bahn, Sabine



Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBP?) expression through the regulation of histone modification at its promoter region in female offspring rat skeletal muscle.  


Maternal nutrition during pregnancy is an important intrauterine environmental factor that can cause persistent alterations of the offspring genome and is associated with potential disease risk later in life. In the present study, we investigated the impact of a maternal low protein diet (LP) on the expression of the transcription factor CCAAT/enhancer-binding protein (C/EBP?) in offspring skeletal muscle. C/EBP? belongs to a family of transcription factors that regulates the expression of genes involved in energy homeostasis and muscle development. We investigated C/EBP? transcriptional regulation from an epigenetic aspect. We observed sex-dependent differences in C/EBP? expression in offspring skeletal muscle subjected to a maternal protein-restricted diet. In female offspring skeletal muscle, both C/EBP? mRNA and protein levels were increased by maternal protein restriction. However, C/EBP? expression was not altered in other tissues or male offspring. Analysis of transcriptional and epigenetic regulation showed acetylated histone 3 and acetylated histone 4 at significantly increased levels at the C/EBP? promoter region in female LP pup's muscle. Phosphoenolpyruvate carboxykinase (PEPCK) gene transcription was also up-regulated in female LP pups through the increased binding of C/EBP? at its promoter. The induction of C/EBP? expression in female offspring skeletal muscle by maternal protein restriction during pregnancy may indicate C/EBP? involvement in signaling response in energy metabolism to a low maternal protein diet. PMID:20930553

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



Response of fetal and newborn piglets to maternal protein restriction during early or late pregnancy.  


Dietary protein restriction during pregnancy has an adverse effect on progeny development, although the importance of the time at which the nutritional insult occurs is unclear. The objective in our study was to test the hypothesis that severe protein restriction during the first trimester of swine pregnancy has a greater detrimental effect on fetal development than restriction in late pregnancy. On the day of mating, primiparous swine were assigned to control (C, 13% protein) or protein-restricted (PR, 0.5% protein) diets and fed in 4 regimens: 1) C diet throughout pregnancy (114 +/- 2 days) (n = 5), 2) PR diet to day 44, C diet to parturition (n = 6), 3) C diet to day 80, PR diet to parturition (n = 8), and 4) PR diet throughout pregnancy (n = 6). In addition, 6 pigs fed C and 7 pigs fed PR diets were killed at day 44 to assess placental and fetal development. Maternal diet had no effect on placental or fetal weight, crown-rump length, or heart girth circumference in 44-day fetuses. Mean birth weight of newborn piglets was 1462, 1291, 1262, and 1064 g for C, PR:C, C:PR, and PR groups, respectively (C greater than PR:C = C:PR greater than PR, p less than 0.01). Plasma total protein and albumin were less (p less than 0.01) in PR than in PR:C and C:PR; all three groups were less than C (p less than 0.01). Liver weight and total liver protein, RNA, and DNA followed the same pattern (C greater than PR:C = C:PR greater than PR, p less than 0.05). Longissimus muscle total protein, RNA, and DNA were greater in group C than in all other groups (p less than 0.01). Maternal protein restriction during early pregnancy produced less developmental impairment than restriction throughout pregnancy, but the magnitude of impairment was similar to that produced by restriction during only the third trimester. The effects of early restriction were manifested at birth, even though none of the indices of stunting were observed at 44 days when the maternal protein restriction was ended. Whether the effects of early versus late restriction show the same mechanism of action has not been determined. PMID:1428413

Pond, W G; Maurer, R R; Mersmann, H J; Cummins, S



Placental Gene Expression Responses to Maternal Protein Restriction in the Mouse  

PubMed Central

OBJECTIVE Maternal protein restriction has been shown to have deleterious effects on placental development, and has long-term consequences for the progeny. We tested the hypothesis that, by the use of microarray technology, we could identify specific genes and cellular pathways in the developing placenta that are responsive to maternal protein deprivation, and propose a potential mechanism for observed gene expression changes. METHODS We fed pregnant FVB/NJ mice from day post coitum 10.5 (DPC10.5) to DPC17.5, an isocaloric diet containing 50% less protein than normal chow. We used the Affymetrix Mouse 430A_2.0 array to measure gene expression changes in the placenta. We functionally annotated the regulated genes, and examined over-represented functional categories and performed pathway analysis. For selected genes, we confirmed the microarray results by use of qPCR. RESULTS We observed 244 probe sets, corresponding to 235 genes, regulated by protein restriction (p < 0.001), with ninety-one genes being up-regulated, and 153 down-regulated. Up-regulated genes included those involved in the p53 pathway, apoptosis, negative regulators of cell growth, negative regulators of cell metabolism and genes related to epigenetic control. Down-regulated genes included those involved in nucleotide metabolism. CONCLUSIONS Microarray analysis has allowed us to describe the genetic response to maternal protein deprivation in the mouse placenta. We observed that negative regulators of cell growth and metabolism in conjunction with genes involved in epigenesis were up-regulated, suggesting that protein deprivation may contribute to growth restriction and long-term epigenetic changes in stressed tissues and organs. The challenge will be to understand the cellular and molecular mechanisms of these gene expression responses.

Gheorghe, Ciprian P.; Goyal, Ravi; Holweger, Joshua D.; Longo, Lawrence D.



Elucidation of thrifty features in adult rats exposed to protein restriction during gestation and lactation.  


Since the introduction of the thrifty phenotype hypothesis, the potential traits of thrift have been described in increasingly broad terms but biochemical and behavioral evidence of thrift has not been well demonstrated. The objective of our studies was to use a rodent model to identify features of thrift programmed by early life protein restriction. Robust programming of thrifty features requires a thrifty nutritional environment during the entire window of developmental plasticity. Therefore, pregnant rats were exposed to a low protein diet throughout the window of developmental plasticity spanning the period of gestation and lactation and its effects on energy acquisition, storage and expenditure in the adult offspring were examined. Maternal protein restriction reduced birth weight and produced long term reductions in body and organ weights in the offspring. Low protein offspring demonstrated an increased drive to seek food as evidenced by hyperphagia that was mediated by changes in plasma leptin and ghrelin levels. Hyperphagia was accompanied by increased efficiency in converting caloric intake into body mass. The higher feed efficiency was mediated by greater insulin sensitivity. Energy expenditure of low protein offspring in locomotion was not affected either in the light or dark phase. However, low protein offspring exhibited higher resting and basal metabolic rates as evidenced by higher core body temperature in the fed and fasted states. The increased thermogenesis was not mediated by thyroid hormones but by an increased sympathetic nervous system drive as reflected by a lower areal bone mineral density and bone mineral content and lower plasma adiponectin and triglyceride levels. Elevated thermogenesis in the low protein offspring possibly offsets the effects of hyperphagia, minimizes their chances of weight gain, and improves survivability. This constellation of metabolic features in the low protein offspring will maximize survival potential in a post natal environment of nutritional scarcity and constitute a thrifty phenotype. PMID:22210394

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



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

PubMed Central

We have examined hepatic, genomic, and metabolic responses to dietary protein restriction in the non-pregnant Sprague-Dawley rat. Animals were pair-fed either a 6 or 24% casein-based diet for 7–10 days. At the end of the dietary period, a microarray analysis of the liver was performed, followed by validation of the genes of interest. The rates of appearance of phenylalanine, methionine, serine, and glucose and the contribution of pyruvate to serine and glucose were quantified using tracer methods. Plasma and tissue amino acid levels, enzyme activities, and metabolic intermediates were measured. Protein restriction resulted in significant differential expression of a number of genes involved in cell cycle, cell differentiation, transport, transcription, and metabolic processes. RT-PCR showed that the expression of genes involved in serine biosynthesis and fatty acid oxidation was higher, and those involved in fatty acid synthesis and urea synthesis were lower in the liver of protein-restricted animals. Free serine and glycine levels were higher and taurine levels lower in all tissues examined. Tracer isotope studies showed an ?50% increase in serine de novo synthesis. Pyruvate was the primary (?90%) source of serine in both groups. Transmethylation of methionine was significantly higher in the protein-restricted group. This was associated with a higher S-adenosylmethionine/S-adenosylhomocysteine ratio and lower cystathione ?-synthase and cystathionine ?-lyase activity. Dietary isocaloric protein restriction results in profound changes in hepatic one-carbon metabolism within a short period. These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine.

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



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

SciTech Connect

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

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



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


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

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



Pre- and/or postnatal protein restriction developmentally programs affect and risk assessment behaviors in adult male rats.  


Developmental programming resulting from a suboptimal intrauterine environment can predispose offspring to a wide-range of lifelong health complications. Little is known about the effects maternal protein restriction during pregnancy and/or lactation has on offspring neurodevelopment. We hypothesized that maternal isocaloric low protein diet during pregnancy and/or lactation would negatively influence male offspring affect and risk assessment behaviors as measured by elevated plus maze and open field tests. Control mothers received 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet) to evaluate effects of maternal diet on offspring risk assessment, anxiety and exploratory behaviors. Elevated plus maze results showed an effect of pre- and/or postnatal diet manipulation in open arm time (p<0.05) with increases seen in the RR (157±22.7s), CR (137±23.2s) and RC (146.8±10.8s) offspring relative to CC (52±8.6s) offspring. This behavior indicates decreased avoidance (less anxiety) and increased exploration by experimental groups. However, in the open field test the RR (17±4.2 entries) offspring entered the center zone less than the CC (35±6.6 entries) offspring thus exhibiting increased anxiety with no other groups showing effects. Elevated levels of corticosterone were measured before, during and after immobilization in the RR compared to CC offspring. These findings show protein restriction during critical periods of development negatively program offspring behavior. The underlying anatomical structures affected remain to be elucidated. PMID:21704656

Reyes-Castro, L A; Rodriguez, J S; Rodríguez-González, G L; Chavira, R; Bautista, C J; McDonald, T J; Nathanielsz, P W; Zambrano, E



Pre and\\/or postnatal protein restriction in rats impairs learning and motivation in male offspring  

Microsoft Academic Search

Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively.

L. A. Reyes-Castro; J. S. Rodriguez; G. L. Rodríguez-González; R. D. Wimmer; T. J. McDonald; F. Larrea; P. W. Nathanielsz; E. Zambrano



Increased transcription activity of rat liver chromatin after protein restriction and limited digestion of nuclei with micrococcus nuclease.  


Protein restriction has been shown to produce either an enhancement or a reduction of transcription activity in vitro. Conditions for an enhanced transcription activity were investigated. Young male rats were fed a complete diet containing either 20% or 3% casein for 6 days. Body weight changed +7.4 g/day and -0.5 g/day, respectively. Liver wet weights were 6.8 and 3.7 g and the DNA amounts/g were 1.31 and 1.67 mg. Liver nuclei were incubated without or with 1 unit micrococcus nuclease (EC per milligram of nuclear DNA, and chromatin was fractionated into a 2,000 x g, a 102,000 x g pellet and a supernatant fraction. In the livers of rats fed a low protein diet, chromatin-bound RNA polymerase I plus III and II activity/mg of fractional and nuclear DNA and soluble RNA polymerase activity were increased, while heparin-stimulated RNA polymerase II activity remained unchanged. An increased number of chains was synthesized by RNA polymerase I plus III without change in chain length and incorporation rate per chain. The length and incorporation rate per chain increased, while the number of chains synthesized by RNA polymerase II did not. After stimulation by heparin, an increased number of short chains was synthesized at a lower rate of incorporation per chain. In the complex chromating structures the capacity for RNA synthesis was determined by specific enzyme activity, RNA chain number and length. PMID:6166733

von der Decken, A; Aström, S; Arrhenius, E K



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


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

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



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.

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



Gestational protein restriction affects trophoblast differentiation.  


Whether and how gestational protein restriction (PR) affects placental development and function remain unknown. To test the hypothesis that PR can affect trophoblast differentiation in mid-and late pregnancy, rats were fed a 20% or an isocaloric 6% protein diet from Day 1 to 14 or 18 of pregnancy and effects of PR on trophoblast differentiation were determined by changes in expressions of marker gene(s) for trophoblast lineages. At Day 18 of pregnancy, PR increased expressions of Esrrb, Id1 andId2 (trophoblast stem cell markers), decreased expressions of Ascl2 (spongiotrophblast cell marker) and Prl2c1 (trophoblast giant cell marker), but did not alter expressions of Gjb3 and Pcdh12(glycogen cell markers) in the junctional zone (JZ). In the labyrinth zone (LZ), PR did not change expressions of Prl2b1 (trophoblast giant cell marker), Gcm1 and Syna (syncytiotrophoblast cell markers), but decrease expression of Ctsq (sinusoidal trophoblast giant cell marker). These results indicate that PR impairs the differentiation of trophoblast stem cell into spongiotrophoblast and trophoblast giant cells in JZ, and formation of sinusoidal trophoblast giant cells in LZ. PMID:23277015

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra



Enzyme Markers of Maternal Malnutrition in Fetal Rat Brain1 )  

Microsoft Academic Search

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase




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 ...


Within-litter variance in rat maternal behaviour.  


As a first step in determining the influence of maternal behaviour on sibling behavioural variance, we tested whether rat mothers differentially interact with neonates within the same litter. We also tested whether fading of an ink-mark on individual pups could provide an index of within-litter variance in maternal licking in laboratory rats. In Study 1, during the first postnatal week we distinguished individual Sprague-Dawley rat pups across 4 litters by placing an ink-mark on the skin and quantified variance in maternal licking frequency toward each pup and compared fading of individual pup marks to the frequency of maternal licks received and to four pup characteristics that could influence mark-fading. In Study 2, neonate mark-fading (a proxy for maternal licking) was compared to adolescent and adult offspring behaviour across 8 litters. Results indicated that: (1) there are substantial and consistent differences in how much rat mothers lick same-sex siblings within a litter, (2) differential licking rates can be documented with a non-observational method (ink-mark-fading), and (3) within-litter variance in maternal behaviour may relate to sibling behavioural variance. The findings indicate a viable research model for future experimental studies on causes and consequences of differential maternal investment within families. PMID:20403416

Cavigelli, Sonia A; Ragan, Christina M; Barrett, Catherine E; Michael, Kerry C



Weight gain and maternal behavior in CCK 1 deficient rats  

Microsoft Academic Search

The OLETF rat model of obesity has been extensively studied as an adult model of hyperphagia-induced obesity. In order to better understand the early circumstances that make OLETF pups obese, we investigated body weight from postnatal day (PND) 1 and examined diurnal maternal behavior over the first three postpartum weeks by undisturbed observations. Male and female OLETF rats weighed significantly

Mariana Schroeder; Orna Zagoory-Sharon; Yael Lavi-Avnon; Timothy H. Moran; Aron Weller



Protein Restriction during Pregnancy Affects Postnatal Growth in Swine Progeny1-2  

Microsoft Academic Search

Protein deficiency during pregnancy af fects fetal development. The critical period, when the fetus is most susceptible to maternal protein deficiency and its effect on neonatal growth, is unknown. Therefore, we studied the effect of a protein-restricted diet during early and late pregnancy and throughout pregnancy on growth of pigs from birth to market weight. Sows were fed a control



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


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

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



Lead-exposure of neonatal rats through maternal milk  

Microsoft Academic Search

Lead-exposed neonatal rats are frequently used as a model for plumbism in children. In most studies,PPb is administered to\\u000a the dam, and it is assumed that the pups are exposed to Pb primarily from the dam's milk. Rat pups, however, are coprophagic\\u000a and begin to consume the maternal feces in their second postnatal week. This experiment was designed to determine

Augusta A. Mylroie; Cynthia Tucker; Linda Rosselli-Austin



Alterations in supraoptic nucleus ultrastructure of maternally behaving virgin rats.  


Adult, nulliparous female rats were induced to behave maternally via constant cohousing with rat pups. After exhibiting maternal behaviors for 3 days, the animals were transcardially perfused, the supraoptic nuclei (SON) excised and examined quantitatively by transmission electron microscopy. Relative to virgin controls, the animals behaving maternally were found to have significant increases in: a) mean number of dendrites in large (9-12) dendritic bundles, b) mean area per single dendritic profile, c) area of the dendritic zone occupied by dendritic profiles and d) size of the dendritic zone. No significant changes were observed in the cell body zone or in the number of double synapses in the dendritic region. The observed changes are likely to be at least in part associated with the oxytocin-containing cells of the SON. These observations suggest a role for the SON in promoting maternal behaviors and constitute a novel demonstration of a neural modification in the mammalian central nervous system that appears conjointly with a complex set of behaviors. PMID:3208155

Salm, A K; Modney, B K; Hatton, G I



Brain 2-deoxyglucose level related to maternal behavior-inducing stimuli in the rat  

Microsoft Academic Search

Levels of [14C]2-deoxyglucose (2-DG), measured autoradiographically, in the medial preoptic area (MPOA), were higher during natural parturition with concurrent maternal behavior than in non-pregnant non-maternal controls, whereas levels in the vomeronasal system were lower in virgin rats made maternal by cohabitation with young than in control and parturient rats. Previous studies have shown that lesions of MPOA disrupt maternal behavior,

M. C. R. Del Cerro; M. A. Perez Izquierdo; J. S. Rosenblatt; B. M. Johnson; P. Pacheco; B. R. Komisaruk



Maternal hypothyroidism in the rat influences placental and liver glycogen stores: fetal growth retardation near term is unrelated to maternal and placental glucose metabolic compromise  

Microsoft Academic Search

Maternal hypothyroidism impairs fetal growth in the rat, but the mechanisms by which this occurs are unknown. Since the fetus derives its glucose supply from the mother, and maternal thyroidectomy may disturb maternal and placental glucose metabolism, we postulated that maternal and\\/or placental glucose metabolic compromise may con- tribute to fetal growth retardation in hypothyroid dams. Feto-placental growth, tissue glycogen

M R Pickard; A J Leonard; L M Ogilvie; P R Edwards; I M Evans; A K Sinha; R P Ekins



Effects of maternal obesity on fasting metabolism in newborn rats.  


Maternal obesity is a risk factor for subsequent fasting hypoglycemia in human infants after birth. To investigate further this problem, we employed an animal model of obesity to study neonatal extrauterine metabolic adaptations in pups of obese and lean rats. Female Sprague-Dawley rats were fed a 'cafeteria diet' to induce obesity prior to and during pregnancy. Prior to mating, the cafeteria fed rats were significantly heavier (449 v. 345 g, P less than 0.001) than the controls. Furthermore, weight gain during pregnancy and weight at term were also significantly greater in the obese rats even though they consumed less food during pregnancy. Pup weights and the number of pups per litter were similar between the two groups. Pups born to obese mothers demonstrated hypoglycemia after being fasted for 150 and 180 min when compared with control pups. Hepatic glycogen stores were increased in the fetus of pups born to obese mothers. Glycogen content in pups born to obese mothers declined minimally after birth and remained greater than hepatic glycogen values in control pups throughout the study. In addition to increased fetal storage of glycogen, fetal hepatic triglyceride content was augmented in pups of obese rats. These triglyceride stores declined and were mobilized during fasting after birth. In contrast, hepatic triglyceride content increased after birth among control rats. These results suggest that maternal obesity results in augmented fetal hepatic tissue stores of both glycogen and triglycerides. Hypoglycemia among pups of excessively obese mothers may be due to attenuated mobilization of hepatic glycogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2401587

Heng, J; Kliegman, R M



Epigenetic Programming of Phenotypic Variations in Reproductive Strategies in the Rat Through Maternal Care  

Microsoft Academic Search

Studies across multiple organisms reveal considerable phenotypic variation in reproductive tac- tics. In some species, this variation is associated with maternal effects in which variation in maternal investment results in stable individual differences in reproductive function. Recent studies with the rat suggest that maternal effects can alter the function of neuroendocrine sys- tems associated with female sexual behaviour as well

N. M. Cameron; D. Shahrokh; A. Del Corpo; S. K. Dhir; M. Szyf; F. A. Champagne; M. J. Meaney



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


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

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



Altered placental development in undernourished rats: role of maternal glucocorticoids.  


Maternal undernutrition (MUN) during pregnancy may lead to fetal intrauterine growth restriction (IUGR), which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs) has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1), 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1) predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC) to corticosterone, although can sometimes drive the opposing (inactivating reaction), and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents) in control and MUN rats at embryonic day 20 (E20). Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3) and amino acids (SLC38A1, 2, and 4). Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC38A1, and SLC38A2 expression, and by increased SLC38A4 expression, in labyrinth zones from the mid- and proximal-horns. In marked contrast to the labyrinth zone, the basal zone, which is the site of hormone production, did not show significant changes in any of these enzymes or transporters. These results suggest that dysregulation of the labyrinth zone GC "barrier", and more importantly decreased nutrient supply resulting from downregulation of some of the amino acid system A transporters, may contribute to suboptimal fetal growth under MUN. PMID:21806804

Belkacemi, Louiza; Jelks, Andrea; Chen, Chun-Hung; Ross, Michael G; Desai, Mina



Central Prolactin Infusions Stimulate Maternal Behavior in Steroid-Treated, Nulliparous Female Rats  

Microsoft Academic Search

A series of experiments were conducted to determine whether and under what conditions central prolactin (PRL) administration would stimulate the onset of maternal behavior in female rats and to identify possible neural sites of PRL action. In each experiment ovariectomized, nulliparous rats whose endogenous PRL levels were suppressed with bromocriptine were tested for maternal behavior toward foster young. In experiments

Robert S. Bridges; Michael Numan; Paul M. Ronsheim; Phyllis E. Mann; Caroline E. Lupini



Reduced brain corticotropin-releasing factor receptor activation is required for adequate maternal care and maternal aggression in lactating rats.  


The brain corticotropin-releasing factor (CRF) system triggers a variety of neuroendocrine and behavioural responses to stress. Whether maternal behaviour and emotionality in lactation are modulated by CRF has rarely been investigated. In the present study, we measured CRF mRNA expression within the parvocellular part of the paraventricular nucleus in virgin and lactating Wistar rats bred for high (HAB) and low (LAB) anxiety-related behaviour or non-selected for anxiety (NAB). Further, we intracerebroventricularly infused synthetic CRF or the CRF receptor (CRF-R) antagonist D-Phe to manipulate CRF-R1/2 non-specifically in lactating HAB, LAB, and NAB dams, and monitored maternal care, maternal motivation, maternal aggression, and anxiety. The CRF mRNA expression in the parvocellular part of the paraventricular nucleus was higher in HAB vs. LAB rats independent of reproductive status. The lactation-specific decrease of CRF mRNA was confirmed in LAB and NAB dams but was absent in HAB dams. Intracerebroventricular CRF decreased maternal care under basal conditions in the home cage in all breeding lines and reduced attack behaviour in HAB and LAB dams during maternal defence. In contrast, D-Phe rescued maternal care after exposure to maternal defence in the home cage without influencing maternal aggression. Furthermore, D-Phe decreased and CRF tended to increase anxiety in HAB/NAB and LAB dams, respectively, suggesting an anxiogenic effect of CRF in lactating females. In conclusion, low CRF-R activation during lactation is an essential prerequisite for the adequate occurrence of maternal behaviour. PMID:23742269

Klampfl, Stefanie M; Neumann, Inga D; Bosch, Oliver J




PubMed Central

Prenatal dietary sodium restriction produces profound developmental effects on rat functional taste responses and formation of neural circuits in the brainstem. Converging evidence indicates that the underlying mechanisms for these effects are related to a compromised nutritional state and not to direct stimulus-receptor interactions. We explored whether early malnourishment produces similar functional and structural effects to those seen following dietary sodium restriction by using a protein deficient, sodium replete diet. To determine if early dietary protein-restriction affects the development of the peripheral gustatory system, multi-fiber neurophysiological recordings were made from the chorda tympani nerve and anterograde track tracing of the chorda tympani nerve into the nucleus of the solitary tract (NTS) was accomplished in rats fed a protein-restricted or a control diet (6% and 20%, respectively). The dietary regimens began on embryonic day 7 and continued until rats were used for neurophysiological recordings (postnatal days (P) 35–50) or for chorda tympani terminal field labeling (P40–50). Responses to a concentration series of NaCl, sodium acetate, KCl, and to 0.50 M sucrose, 0.03 M quinine-HCl, and 0.01 N HCl revealed attenuated responses (30–60%) to sodium-specific stimuli in rats fed the 6% protein diet compared with those fed the 20% protein diet. Responses to all other stimuli were similar between groups. Terminal field volumes were nearly twofold larger in protein-restricted rats compared with controls, with the differences located primarily in the dorsal-caudal zone of the terminal field. These results are similar to the results seen previously in rats fed a sodium-restricted diet throughout pre- and postnatal development, suggesting that dietary sodium- and protein-restriction share similar mechanisms in altering gustatory development.




Parturition influences initial pup preferences at later onset of maternal behavior in primiparous rats.  


Initial maternal responsiveness as a function of varying pup stimuli was assessed in primiparous Long-Evans rats. Pups were removed during parturition and the dams tested beginning 24 hr later. These dams were most likely to respond maternally towards newborn (0-2-day-old) rat pups (100%) and 6-8-day-old hamsters, which are the size of newborn rats (83.3%). In contrast, dams were significantly less likely to respond maternally towards newborn hamsters (50%) and 8-10-day-old rats (16.7%), pups which are half as large and twice as large, respectively, as newborn rats; indeed, dams were likely to attack these pups (33.3% and 25%, respectively). The maternal response (less than or equal to 1 hr) to dead newborn rats was similar to that towards live newborn rats, except that fewer dams retrieved dead pups rapidly (less than or equal to 1 min). Cesarean-delivered dams did not display higher maternal responsiveness towards 0-2 than towards 8-10-day-old rats. Further, whereas no parturition-experienced dam displayed infanticide towards newborn rats, 21.9% of primiparous Cesarean-delivered dams did. Thus, the exogenous and/or endogenous stimuli associated with parturition enhance selective maternal responsiveness and diminish infanticide towards pups the size of newborn rats. PMID:3903798

Stern, J M



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

PubMed Central

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

Zhao, Changjiu; Li, Ming



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


The behavioral mechanisms underlying antipsychotic-induced maternal behavior deficits were examined in the present study. Different groups of postpartum rats were treated with haloperidol (0.1 mg/kg), clozapine (10.0 mg/kg), chlordiazepoxide (5.0 mg/kg, an anxiolytic) or vehicle (0.9% saline) on Days 4 and 6 postpartum and their maternal behaviors were tested under either pup-separation (e.g. pups were removed from their mothers for 4 h before testing) or no-pup-separation condition. Maternal behavior and drug-induced sedation were further tested for 3 days from Day 8 to 12 postpartum. Results show that pup-separation, which putatively increases maternal motivation, did significantly shorten clozapine-elongated pup approach latency, increase pup licking and nursing but fail to reverse the deficits in pup retrieval and nest building in the lactating rats treated with haloperidol and clozapine. Repeated haloperidol treatment produced a progressively enhanced disruption on pup retrieval and nest building and an attenuated sedation. In contrast, clozapine showed a progressively diminished disruption on pup retrieval and a concomitantly diminished sedative effect. Based on these findings, we suggest that antipsychotic drugs disrupt active maternal responses at least in part by suppressing maternal motivation, and drug-induced sedation also contributes to this disruptive effect, especially with clozapine. PMID:19041338

Zhao, Changjiu; Li, Ming



Effects of maternal oral morphine consumption on neural tube development in Wistar rats  

Microsoft Academic Search

Opiate abuse during pregnancy may result in abnormal nervous system function. In order to evaluate the effects of morphine on the development of the nervous system, the present study focused on the effects of maternal morphine consumption on neural tube development in Wistar rats.Female Wistar rats (250–300 g) were crossed with male rats and coupling time was recorded (embryonic day

Shiva Nasiraei-Moghadam; Hedayat Sahraei; Hossein Bahadoran; Mehrangiz Sadooghi; Seyed Hossein Salimi; Gholam Reza Kaka; Hossein Imani; Hossein Mahdavi-Nasab; Hossein Dashtnavard



Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats  

Microsoft Academic Search

The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB),

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



Pubertal decline in maternal responsiveness in Long-Evans rats: maturational influences.  


Latency to onset of maternal behavior increases progressively from the weanling to the peripubertal period in female and male Long-Evans rats. Gonadectomy or hypophysectomy on day 21 had no influence on the pubertal decline in maternal responsiveness. Apparently, inhibitory neural pathways mature which are independent of pituitary hormonal influences. PMID:3685167

Stern, J M




PubMed Central

A previous report that the offspring of outbred Sprague-Dawley rats, born of mothers presensitized or tolerant with respect to tissue antigens of the Lewis strain, and reinoculated with Lewis cells during their pregnancy, reject test grafts of Lewis skin in an accelerated manner has been confirmed. This "maternally induced" alteration in reactivity of the progeny has been found to be long lasting, immunologically specific, and probably not due to transfer of humoral antibody. It has been established that the reexposure of the mothers to donor cellular antigen during pregnancy augmented the influence of the prior states of tolerance or sensitivity. To obviate the complications inherent in working with the outbred Sprague-Dawley rats, the key experiments summarized above were repeated with isogenic Fischer rats as parents and Lewis rats as the tissue donors as before. With this combination it was found that a state of prior sensitization or tolerance in the mothers resulted in the apparent induction of tolerance in some of their progeny. Reinoculation of either the tolerant or sensitized mothers during pregnancy slightly increased the incidence and degree of impairment of their offsprings' capacity to reject Lewis skin grafts. A single intraperitoneal injection of 100 x 106 million Lewis lymphoid cells into normal Fischer rats in the 14th–16th day of pregnancy also weakened the reactivity of their progeny to Lewis test grafts. Further to test the premise that this weakened reactivity might be due to maternal induction of tolerance, by antenatal transmission of alien cells, the lymphohematopoietic tissue system of adult Fischer females was replaced by that from Lewis donors with the aid of cyclophosphamide. It was anticipated that when these animals were mated with Fischer males, sufficient Lewis leukocytes might cross the placentas to induce high degrees of tolerance. Although normal sized healthy litters were born, about 50% of the infants succumbed to graft-versus-host (GVH) or runt disease within 40 days, many of them giving evidence of being tolerant of Lewis grafts. The mothers, too, developed chronic GVH disease. The offspring of Fischer females made chimeric with cells from (Fischer x Lewis)F1 hybrid donors, as well as their mothers, remained healthy. Intraperitoneal injection of normal Fischer females, in the 15th–17th day of pregnancy, with 100 million lymphoid cells from specifically sensitized Lewis rats, also caused fatal runt disease to develop in about 50% of their offspring, but left the mothers unscathed. Taken together, these various findings indicate that in some genetic contexts at least the extent of the natural surreptitious transplacental cellular traffic can be considerably augmented experimentally, though how this comes about and why lymphocytic cells that are foreign to the mother can apparently gain access to fetuses more readily than her own cells remain to be determined.

Beer, Alan E.; Billingham, R. E.; Yang, S. L.



Early postnatal diazepam exposure facilitates maternal behavior in virgin female rats  

Microsoft Academic Search

Virgin female rats do not display maternal behavior if they are not exposed to the pups during several days. This exposure is called induction. In this work we have studied the effects of early postnatal (PO-P16) diazepam (DZ) administration (1 and 2.5 mg\\/kg, SC) on the display of maternal behavior of virgin female rats when adults. Although we did not

M. C. R. Del Cerro; M. A. P. Izquierdo; C. Perez-Laso; M. Rodriguez-Zafra; A. Guillamon; S. Segovia



Adolescent Exposure to Chronic Delta9Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats  

Microsoft Academic Search

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

Lydie J Morel; Bruno Giros; Valérie Daugé



Arginine Vasopressin V1a Receptor Antagonist Impairs Maternal Memory in Rats  

PubMed Central

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

Nephew, Benjamin C.; Bridges, Robert S.



Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats  

PubMed Central

The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ.

Furuta, Miyako; Bridges, Robert S.



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

PubMed Central

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

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



How early maternal separation and juvenile experience with pups affect maternal behavior and emotionality in adult postpartum rats  

Microsoft Academic Search

To assess the effects of preweaning and juvenile experiences on adult maternal behavior, two experiments were completed. In\\u000a Experiment 1, pups were separated for long periods or short periods or were left undisturbed over the 1st week. Following\\u000a weaning, the rats were exposed to foster pups over a 5-day period or were left undisturbed. There were no effects of early

Stephanie L. Rees; Alison S. Fleming



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

National Technical Information Service (NTIS)

A short review is presented in Chinese of the present status of studies in rats to determine the effects of maternal diet upon growth and development of the progeny. Dietary restriction of the female rat during pregnancy and lactation has been shown to pr...

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




Microsoft Academic Search

The effects of maternal protein and\\/or calorie deficiency during gestation in rats on subsequent growth, body composition, cell size and cell number in organs of progeny were studied into maturity. Female rats were fed the experimental diets for two weeks before mating and throughout gestation. Protein deficiency caused a significant decrease in birth weight, litter size and fertility and a

Katrine I McLleod; RB Goldrick; HM Whyte



The Contribution of Maternal Iron Stores to Fetal Iron in Rats  

Microsoft Academic Search

The contribution of maternal iron stores to fetal iron content in rats of the Sprague-Dawley strain has been examined. 59Fe was injected intramuscularly into two groups of rats to label iron in the liver. Two weeks later one group was bred. After delivery of fetuses, all animals were killed and examined for distribution of radioactivity and nonheme iron content in



Variations in maternal care in the rat as a mediating influence for the effects of environment on development  

Microsoft Academic Search

Variations in maternal care have been widely considered as a critical influence in development. In the rat, variations in maternal behavior, particularly in licking\\/grooming, regulate the development of endocrine, emotional and cognitive responses to stress. These studies form the basis of a potentially useful model for the study of maternal effects in mammals. In this paper we provide a detailed

Frances A. Champagne; Darlene D. Francis; Adam Mar; Michael J. Meaney



BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels?  


Brain-derived neurotrophic factor (BDNF) is of interest because of its putative role in stress and psychiatric disorders. Maternal separation is used as an animal model of early-life stress and of irritable bowel syndrome (IBS). Animals exposed to the paradigm show altered gut function together with heightened levels of arousal and corticosterone. Some probiotic organisms have been shown to be of benefit in IBS and influence the brain-gut axis. Our objective was to investigate the effects of maternal separation on BDNF under basal conditions and in response to the probiotic Bifidobacterium breve 6330. The study implemented the maternal separation model which we have previously described. Polymerase chain reaction and in situ hybridisation were performed to measure the effect of maternal separation on both BDNF total variants and BDNF splice variant (exon) IV in the hippocampus. Maternally separated and non-separated rats were treated with B. breve 6330, to investigate the effect of this probiotic on BDNF total variant and BDNF exon IV expression. Maternal separation increased BDNF total variants (P<0.01), whilst having no effect on BDNF exon IV. B. breve 6330 increased BDNF total variants (P<0.01), and decreased BDNF splice variant IV, in non-separated rats (P<0.01). B. breve 6330 did not alter BDNF levels in the maternally separated rats. Maternal separation caused a marked increase in BDNF in the hippocampus. While B. breve 6330 influenced BDNF in normal animals, it had no significant effect on BDNF in those which were maternally separated. We have demonstrated that an orally administered probiotic can influence hippocampal BDNF. PMID:21986359

O'Sullivan, E; Barrett, E; Grenham, S; Fitzgerald, P; Stanton, C; Ross, R P; Quigley, E M M; Cryan, J F; Dinan, T G



Effects of Brain Antiestrogen Implants on Maternal Behavior and on Postpartum Estrus in Pregnant Rats  

Microsoft Academic Search

To test the hypothesis that the onset of maternal behavior is stimulated by estrogen, we examined the effects of medial preoptic area (MPOA) or ventromedial hypothalamus (VMH) implants of the antiestrogen 4-hydroxytamoxifen (OH-TAM) on pre- and postpartum maternal behavior and on postpartum estrus in rats. On day 20 of pregnancy, animals were implanted bilaterally with OH-TAM or cholesterol cannulae into

Harry B. Ahdieh; Anne D. Mayer; Jay S. Rosenblatt



A Dose–Response Study of Chronic Cocaine on Maternal Behavior in Rats  

Microsoft Academic Search

To determine if there was a dose–response relationship with regard to cocaine treatment and maternal behavior exhibited by lactating rats at doses that had not been previously investigated, we examined the effects of three doses of chronic cocaine administration throughout gestation on both onset and established maternal behavior. Dams were injected (SC) with 6.3, 13, or 25 mg\\/kg cocaine HCl

Christina J. Nelson; Kathleen E. Meter; Cheryl H. Walker; Andy A. Ayers; Josephine M. Johns



Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression  

Microsoft Academic Search

In order to study the gene–environment interaction as well as investigate prophylactic\\/ameliorative effects of early intervention on development of adult life psychopathology, we superimposed maternal separation on an animal model of depression the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL) rats and studied behavior following treatment with escitalopram. Animals were maternally separated for 180

Aram El Khoury; Susanne H. M. Gruber; Arne Mørk; Aleksander A. Mathé



Voluntary exercise in pregnant rats positively influences fetal growth without initiating a maternal physiological stress response.  


The effects of increased physical activity during pregnancy on the health of the offspring in later life are unknown. Research in this field requires an animal model of exercise during pregnancy that is sufficiently strenuous to cause an effect but does not elicit a stress response. Previously, we demonstrated that two models of voluntary exercise in the nonpregnant rat, tower climbing and rising to an erect bipedal stance (squat), cause bone modeling without elevating the stress hormone corticosterone. In this study, these same models were applied to pregnant rats. Gravid Wistar rats were randomly divided into three groups: control, tower climbing, and squat exercise. The rats exercised throughout pregnancy and were killed at day 19. Maternal stress was assessed by fecal corticosterone measurement. Maternal bone and soft tissue responses to exercise were assessed by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry. Maternal weight gain during the first 19 days of pregnancy was less in exercised than in nonexercised pregnant control rats. Fecal corticosterone levels did not differ between the three maternal groups. The fetuses responded to maternal exercise in a uterine position-dependent manner. Mid-uterine horn fetuses from the squat exercise group were heavier (P < 0.0001) and longer (P < 0.0001) and had a greater placental weight (P = 0.001) than those from control rats. Fetuses from tower-climbing dams were longer (P < 0.0001) and had heavier placentas (P = 0.01) than those from control rats, but fetal weight did not differ from controls. These models of voluntary exercise in the rat may be useful for future studies of the effects of exercise during pregnancy on the developmental origins of health and disease. PMID:21307360

Rosa, Brielle V; Firth, Elwyn C; Blair, Hugh T; Vickers, Mark H; Morel, Patrick C H



On the maternal transfer of 4-aminobiphenyl in rats.  


The potential for 4-aminobiphenyl (4-ABP) to be transferred from circulating blood into the milk of lactating Sprague-Dawley rats was determined. The distribution of 14C-labeled 4-ABP into milk was examined at time intervals of less than 1, 20, 60, 120, 240 and 480 min after i.v. dose administration. Elimination of radioactivity from blood and milk was determined to be biphasic. The levels of 4-ABP and/or metabolites were lower in milk than in blood at all time points examined. The levels of radioactivity detected in blood declined less rapidly than in milk. That is, the percent of the dose per ml of blood declined from 0.81-0.45, while the percent of the dose per ml of milk declined from 0.38-0.06 during the 8 h time period. The radioactivity present in milk was partially extractable with ethyl acetate with 43% of the radioactivity being extractable at the earliest time point while only 16% was extractable after 8 h. The level of radioactivity associated with the protein precipitate of the milk samples increased from 4-21% within 4 h after treatment. The potential of 4-ABP or its metabolites to exert a genotoxic effect on newborn pups via maternal transfer was also examined. Dams were treated on day 1 post partum and then daily with 4-ABP (10 mg/kg) in corn oil or corn oil alone for 2 weeks. Each experimental group had four liters of pups each containing 5 pups. Pups were sacrificed at 15 days of age, separated by sex and the levels of 4-ABP:DNA adducts in liver determined using 32P-postlabeling. DNA adduct profiles were similar between male and female pups with total adduct levels of 332 and 338 fmol of adducts/mg of DNA, respectively. These results indicate that the genotoxic effects of 4-ABP can be transmitted from exposed dams to the nursing offspring. PMID:2912573

La Voie, E J; Stern, S L; Burrill, C; Weyand, E H



Impact of taurine supplementation on blood pressure in gestational protein-restricted offspring: Effect on the medial solitary tract nucleus cell numbers, angiotensin receptors, and renal sodium handling.  


OBJECTIVE: The current study considers changes of the postnatal brainstem cell number and angiotensin receptors by maternal protein restriction (LP) and LP taurine supplementation (LPT), and its impact on arterial hypertension development in adult life. METHODS: and results:The brain tissue studies were performed by immunoblotting, immunohistochemistry, and isotropic fractionator analysis. The current study shows that elevated blood pressure associated with decreased fractional urinary sodium excretion (FENa) in adult LP offspring was reverted by diet taurine supplementation. Also, that 12-day-old LP pups present a reduction of 21% of brainstem neuron counts, and, immunohistochemistry demonstrates a decreased expression of type 1 angiotensin II receptors (AT1R) in the entire medial solitary tract nuclei (nTS) of 16-week-old LP rats compared to age-matched NP and LPT offspring. Conversely, the immunostained type 2 AngII (AT2R) receptors in 16-week-old LP nTS were unchanged. CONCLUSION: The present investigation shows a decreased FENa that occurs despite unchanged creatinine clearance. It is plausible to hypothesize an association of decreased postnatal nTS cell number, AT1R/AT2R ratio and FENa with the higher blood pressure levels found in taurine-deficient progeny (LP) compared with age-matched NP and LPT offspring. PMID:23468165

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



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

Microsoft Academic Search

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

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



Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats  

Microsoft Academic Search

BackgroundMaternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the

Patrick O. McGowan; Matthew Suderman; Aya Sasaki; Tony C. T. Huang; Michael Hallett; Michael J. Meaney; Moshe Szyf; Angela Sirigu



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

Microsoft Academic Search

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

S. M. Chanda; C. N. Pope



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

Microsoft Academic Search

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

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



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.



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


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

Hancock, Stephanie; Grant, Virginia




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...


The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat  

Microsoft Academic Search

Summary  Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall

M. Dunlop; R. G. Larkins; J. M. Court



Maternal Contributions to Sensory Experience in the Fetal and Newborn Rat (Rattus norvegicus )  

Microsoft Academic Search

Using videographic analyses, we identified and quantified maternal contributions to the sensory environment of the perinatal rat (Rattus norvegicus) by analyzing, from the offspring's perspective, the dam's activities during gestation, labor, and delivery. Our observations indicate that pregnant females remain highly active during the final week of gestation, as compared with nonpregnant control animals. Exploratory movements, feeding, drinking, self-grooming, and

April E. Ronca; Christopher A. Lamkin; Jeffrey R. Alberts



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

Microsoft Academic Search

In a previous study, we showed that exposure of rats to dexamethasone (Dex) selectively in late pregnancy produces permanent induction of hepatic phospho- enolpyruvate carboxykinase (PEPCK) expression and hyperglycaemia in the adult offspring. The mechanisms by which glucocorticoids cause this programming are unclear but may involve direct actions on the fetus\\/neonate, or glucocorticoids may act indirectly by affecting maternal postnatal

M J Nyirenda; LAM Welberg; J R Seckl



Early maternal separation alters neuropeptide Y concentrations in selected brain regions in adult rats  

Microsoft Academic Search

Human and animal studies support the involvement of neuropeptide Y (NPY) in the pathophysiology of depression. Thus, hippocampal NPY-LI is decreased in genetic models of depression, the Flinders Sensitive Line and Fawn Hooded rats. Maternal ‘deprivation’ has been identified as one risk factor in the development of psychopathology, including depression in adulthood. In view of these findings we hypothesized that

P. A Jiménez-Vasquez; A. A Mathé; J. D Thomas; E. P Riley; C. L Ehlers



Ultrasonic vocalizations and maternal-infant interactions in a rat model of fetal alcohol syndrome  

Microsoft Academic Search

When isolated from their dams and littermates, rat pups emit ultrasonic vocalizations to elicit attention and retrieval from their dams. This study examined the effects of perinatal alcohol exposure on ultrasonic vocalizations and maternal-infant interactions. Alcohol was administered throughout gestation to the dams and during the early postnatal period to the pups. Control groups consisted of a nontreated control and

Melissa D. Marino; Kim Cronise; Joaquin N. Lugo; Sandra J. Kelly



Differential regional brain responses to induced maternal behavior in rats measured by cytochrome oxidase immunohistochemistry  

Microsoft Academic Search

Maternal behavior (MB) in rats is expressed under neural control of vomeronasal structures. Some of these regions exert an inhibitory role, such as the accessory olfactory bulb (AOB), while others exert an excitatory role, such as the medial preoptic area (MPOA). In previous studies, using 2-DG as a marker for neuron activity at neuron terminal level, we reported that AOB

Carmen Pérez-Laso; Sandra Rubio; José Luís R. Martín; Francisco Gómez; Santiago Segovia



The prostate of weaned pups is altered by maternal malnutrition during lactation in rats  

Microsoft Academic Search

The aim of this study was to evaluate the effects of maternal malnutrition during lactation on prostate growth and estradiol serum concentration in the prostate of pups. At delivery, nine Wistar rats were separated into three groups: control group (C) with free access to a standard laboratory diet containing 22% protein; protein–energy-restricted group (PER) with free access to an isoenergy

Cristiane da F. Ramos; Marcio A. Babinski; Waldemar S. Costa; Francisco J. B. Sampaio



Maternal malnutrition during lactation reduces skull growth in weaned rat pups: Experimental and morphometric investigation  

Microsoft Academic Search

The purpose of the present study was to evaluate the effects of maternal protein and energy restriction during lactation on the bodyweight and skull dimensions of pups at weaning. At parturition, Wistar rat dams were randomly assigned to the following groups: (i) control group (C), free access to a standard laboratory diet containing 23% protein; (ii) protein-energy-restricted group (PER), free

Rodrigo M. Fernandes; Antonio V. Abreu; Roberto B. Silva; Danielle F. Silva; Gisele L. Martinez; Marcio A. Babinski; Cristiane F. Ramos



Maternal Hyperglycemia Modifies Extracellular Matrix Signaling Pathways in Neonatal Rat Lung  

Microsoft Academic Search

Background: Maternal diabetes is associated with numerous adverse effects in fetal and neonatal organs, including the lungs. Objective: To investigate the effects of intrauterine hyperglycemia on neonatal lung biological signaling, we performed a microarray analysis in the lungs of four 14-day-old rat pups born to a hyperglycemic dam and in four age mate control pup lungs. Methods: Total RNA was

Anna Koskinen; Asta Laiho; Heikki Lukkarinen; Pekka Kääpä; Hanna Soukka



Influence of the Destabilisation of the Maternal Digestive Microf lora on That of the Newborn Rat  

Microsoft Academic Search

By destabilising the digestive flora of pregnant rats by antibiotic treatment, it was shown that part of the digestive microflora of the neonate originated from the maternal faeces. A mixture of ampicillin, bacitracin neomycin and streptomycin associated with nystatin were administered ad libitum at three different times, 1-3, 3-5, and more than 5 days before the estimated date of littering.

A. Brunel; Ph. Gouet




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...


Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study  

PubMed Central

Background Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY) rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1) in SHR striatum. Consistent with this observation, the dopamine clearance time (T100) was increased in SHR. These results suggest that the chronic mild stress of maternal separation impaired the function of striatal DAT in SHR. Conclusions The present findings suggest that maternal separation failed to alter the behaviour of SHR in the open field and elevated plus maze. However, maternal separation altered the dopaminergic system by decreasing surface expression of DAT and/or the affinity of DAT for dopamine, increasing the time to clear dopamine from the extracellular fluid in the striatum of SHR.



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

PubMed Central

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

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



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.



Effect of fetal growth on maternal protein metabolism in postabsorptive rat  

SciTech Connect

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

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



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



Central Lactogenic Regulation of Maternal Behavior in Rats: Steroid Dependence, Hormone Specificity, and Behavioral Potencies of Rat Prolactin and Rat Placental Lactogen I  

Microsoft Academic Search

Adult virgin female rats display maternal behavior when contin- uously exposed to foster young for 5-6 days. Central infusions of PRL or placental lactogens (PLs) together with systemic treatment of pro- gesterone (P) and estradiol (E2) stimulate maternal behavior in 1-2 days. In the present set of studies, it was asked whether the actions of lactogenic hormones are dependent upon




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

Microsoft Academic Search

Mercury vapor released from a single amalgam restoration in pregnant rats and mercury concentrations in maternal and fetal rat tissues were studied. Dental treatment was given on day 2 of pregnancy. Mercury concentration in air sample drawn from the metabolism chamber with the rat was measured serially for 24 h on days 2, 8 and 15 of pregnancy. An average

Yoshifumi Takahashi; Shozo Tsuruta; Jiro Hasegawa; Yoichiro Kameyama; Minoru Yoshida



Late-onset exercise in female rat offspring ameliorates the detrimental metabolic impact of maternal obesity.  


Rising rates of maternal obesity/overweight bring the need for effective interventions in offspring. We observed beneficial effects of postweaning exercise, but the question of whether late-onset exercise might benefit offspring exposed to maternal obesity is unanswered. Thus we examined effects of voluntary exercise implemented in adulthood on adiposity, hormone profiles, and genes involved in regulating appetite and metabolism in female offspring. Female Sprague Dawley rats were fed either normal chow or high-fat diet (HFD) ad libitum for 5 weeks before mating and throughout gestation/lactation. At weaning, female littermates received either chow or HFD and, after 7 weeks, half were exercised (running wheels) for 5 weeks. Tissues were collected at 15 weeks. Maternal obesity was associated with increased hypothalamic inflammatory markers, including suppressor of cytokine signaling 3, TNF-?, IL-1?, and IL-6 expression in the arcuate nucleus. In the paraventricular nucleus (PVN), Y1 receptor, melanocortin 4 receptor, and TNF-? mRNA were elevated. In the hippocampus, maternal obesity was associated with up-regulated fat mass and obesity-associated gene and TNF-? mRNA. We observed significant hypophagia across all exercise groups. In female offspring of lean dams, the reduction in food intake by exercise could be related to altered signaling at the PVN melanocortin 4 receptor whereas in offspring of obese dams, this may be related to up-regulated TNF-?. Late-onset exercise ameliorated the effects of maternal obesity and postweaning HFD in reducing body weight, adiposity, plasma leptin, insulin, triglycerides, and glucose intolerance, with greater beneficial effects in offspring of obese dams. Overall, hypothalamic inflammation was increased by maternal obesity or current HFD, and the effect of exercise was dependent on maternal diet. In conclusion, even after a significant sedentary period, many of the negative impacts of maternal obesity could be improved by voluntary exercise and healthy diet. PMID:23928377

Bahari, Hasnah; Caruso, Vanni; Morris, Margaret J



Predation threat exerts specific effects on rat maternal behaviour and anxiety-related behaviour of male and female offspring  

Microsoft Academic Search

Differences in the rate of maternal behaviours received by rodent offspring are associated with differential programming of molecular and behavioural components of anxiety and stress-related functions. To determine the degree to which maternal behaviours are sensitive to environmental conditions, Long–Evans rat dams were exposed to the odour of a predator (cat) at two different time points during the first week

Rahia Mashoodh; Christopher J. Sinal; Tara S. Perrot-Sinal



Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus  

Microsoft Academic Search

Maternal care in the rat influences hippocampal development, synaptic plasticity and cognition. Previous studies, however, have examined animals under minimally stressful conditions. Here we tested the hypothesis that maternal care influences hippocampal function differently when this structure is exposed to corticosteroid and noradrenergic hormones, which are elevated during the early phase of a stress response. In the adult male offspring

Rosemary C. Bagot; Felisa N. van Hasselt; Danielle L. Champagne; Michael J. Meaney; Harm J. Krugers; Marian Joëls



Expression of intracellular progesterone receptors in rat brain during different reproductive states, and involvement in maternal behavior  

Microsoft Academic Search

Progesterone is one of a complex of hormones which influences the occurrence of maternal behavior in rats. The present study provides information on progesterone's mechanism and possible neural site(s) of action with respect to maternal responsiveness. Progesterone can exert cellular effects by acting on membrane receptors or by acting on intracellular receptors. In the first experiment we show that RU

Michael Numan; Jennifer K. Roach; M. Cruz R. del Cerro; Antonio Guillamón; Santiago Segovia; Teige P. Sheehan; Marilyn J. Numan



Alteration of pituitary hormone-immunoreactive cell populations in rat offspring after maternal dietary exposure to endocrine-active chemicals  

Microsoft Academic Search

We previously performed dose–response studies of genistein, diisononyl phthalate, 4-nonylphenol, methoxychlor (MXC), and bisphenol A to examine the impact of maternal dietary exposure from gestational day 15 to postnatal day 10 on the development of rat reproductive system in later life. Among the chemicals MXC alone showed typical estrogenic effects only at the maternally toxic 1200 ppm. The present study was

Naoya Masutomi; Makoto Shibutani; Hironori Takagi; Chikako Uneyama; Kyoung-Youl Lee; Masao Hirose



Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats.  


Inflammation-associated foetal loss is often linked to maternal coagulopathies. Here, we characterised the role of maternal inflammation in the development of various systemic maternal coagulopathies and foetal death during mid-to-late gestation in rats. Since nitric oxide (NO) functions as an inhibitor of platelet aggregation and anti-oxidant, we also tested whether the NO mimetic nitroglycerin (glyceryl trinitrate, GTN) prevents inflammation-associated coagulopathies and foetal death. To induce chronic inflammation, pregnant Wistar rats were injected with low-doses of lipopolysaccharide (LPS; 10-40 ?g/kg) on gestational days (GD) 13.5-16.5. To determine whether the effects of inflammation are mediated by tumour necrosis factor-? (TNF-?), the TNF-? inhibitor etanercept was injected on GD 13.5 and 15.5. Controls consisted of rats injected with saline. GTN was administered to LPS-treated rats via daily application of a transdermal patch on GD 12.5-16.5. Using thromboelastography (TEG), various coagulation parameters were assessed on GD 17.5; foetal viability was determined morphologically. Reference coagulation parameters were established based on TEG results obtained from control animals. LPS-treated rats exhibited distinct systemic coagulopathies: hypercoagulability, hypocoagulability, hyperfibrinolysis, and disseminated intravascular coagulation (DIC) stages I and III. A specific foetal death coagulation phenotype was observed, implicating TEG as a potential tool to identify inflammation-induced haemostatic alterations associated with pregnancy loss. Treatment with etanercept reduced the incidence of coagulopathy by 47%, while continuous delivery of GTN prevented foetal death and the inflammation-induced coagulopathies. These findings provide a rationale for investigating the use of GTN in the prevention of maternal coagulopathies and inflammation-mediated foetal death. PMID:22274747

Cotechini, Tiziana; Othman, Maha; Graham, Charles H



Early repeated maternal separation induces alterations of hippocampus reelin expression in rats.  


The long-term effects of repeated maternal separation (MS) during early postnatal life on reelin expression in the hippocampus of developing rats were investigated in the present study. MS was carried out by separating Wistar rat pups singly from their mothers for 3 h a day during postnatal days (PND) 2-14. Reelin mRNA and protein levels in the hippocampus were determined using qRT-PCR and Western blotting, at PND 22, PND 60 and PND 90. MS resulted in the loss of body weight in the developing rats, and reelin mRNA and protein levels in the hippocampus generally were down-regulated over the developing period, but the reelin mRNA and protein levels in the hippocampus of 90-day-old male rats were up-regulated. These findings suggest that the long-term effects of MS on the expression levels of hippocampal reelin mRNA and protein depends on the age at which the stressed rats' brains were collected; reelin had important implications for the maternal-neonate interaction needed for normal brain development. In conclusion, repeated MS occurring during early postnatal life may cause the alterations of hippocampal reelin expression with the increasing age of developing rats. PMID:23385810

Zhang, Jianlong; Qin, Lina; Zhao, Hu



Maternal behavior as an early modulator of neurobehavioral offspring responses by Sprague-Dawley rats.  


Maternal care plays an important role as an early modeler of neurodevelopment and brain function, and its effects remain until adulthood. Such modeling or programming has shown to influence the stress response and represents a key susceptibility factor in the development of mood disorders. In order to characterize such process which is still not clear, male offspring were classified in animals with low, medium and high licking/grooming (LG) according to the maternal behavior. Juvenile animals were subjected to the open field test (OFT) and the forced swimming test (FST), and offspring of low and high LG mothers were compared. Seven days after the FST, neurochemical and gene expression analyses were carried out in order to identify possible changes on relevant targets. Maternal care did determine locomotor behaviors in the OFT, supporting an anxiogenic effect of low maternal investment. This effect seems to be associated with the serotonergic systems in both nucleus accumbens (NAc) and hippocampus (HPC), since offspring of low LG mothers showed decreased 5-HT neurotransmission in those brain regions compared with animals of high LG mothers. Furthermore, TrkB expression was higher in offspring of high LG compared to the group of low LG mothers, supporting its influence as a mechanistic intermediate of such effect, at least in the NAc. Taken together, these findings strongly support the influence of differential maternal care on the neurodevelopment and responsivity of juvenile rats. PMID:23018125

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



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

Microsoft Academic Search

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

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



Maternal Ghrelin Plays an Important Role in Rat Fetal Development during Pregnancy  

Microsoft Academic Search

Ghrelin, an acylated peptide serving as an endogenous ligand forGHsecretagoguereceptor(GHS-R),wasoriginallyisolated from rat and human stomach. In this study, we report the critical role of maternal ghrelin in fetal development. High levels of ghrelin receptor (GHS-R) mRNA were detected in various peripheral fetal tissues beginning at embryonic d 14 and lasting until birth. Fetal GHS-R expression was also con- firmed in

Keiko Nakahara; Mari Nakagawa; Yukiko Baba; Miho Sato; Koji Toshinai; Yukari Date; Masamitsu Nakazato; Masayasu Kojima; Mikiya Miyazato; Hiroyuki Kaiya; Hiroshi Hosoda; Kenji Kangawa; Noboru Murakami



Long-term Effects of Maternal Magnesium Restriction on Adiposity and Insulin Resistance in Rat Pups  

Microsoft Academic Search

Objective:We investigated the long-term effects of maternal\\/postnatal magnesium (Mg) restriction on adiposity, glucose tolerance, and insulin secretion in the offspring and the probable biochemical mechanisms associated with them.Methods and Procedures:Female weanling Wistar\\/NIN (WNIN) rats received a control diet or 70% Mg-restricted (MgR) diet for 9 weeks and mated with control males. A third of the restricted dams were shifted to

Lagishetty Venu; Inagadapa J. N. Padmavathi; Yedla D. Kishore; Nandiwada V. Bhanu; Kalashikam R. Rao; Pothaganti B. Sainath; Manisha Ganeshan; Manchala Raghunath



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

Microsoft Academic Search

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

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



Bisphenol-A exposure during pregnancy and lactation affects maternal behavior in rats  

Microsoft Academic Search

In mammals, endogenous estrogens are crucial for sexual differentiation during the perinatal period, and the modulation in adulthood of many neuroendocrine and behavioral functions involved in reproduction. In rats, the estrogenic environment during pregnancy and lactation affects directly maternal behavior. This experiment was aimed to test whether the exposure to the estrogenic compound bisphenol-A (BPA; 0.040mg\\/kg\\/die, orally) of adult female

Daniele Della Seta; Isabelle Minder; Francesco Dessì-Fulgheri; Francesca Farabollini



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

Microsoft Academic Search

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

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



Effects of novel antipsychotics, amisulpiride and aripiprazole, on maternal behavior in rats  

Microsoft Academic Search

Rationale  Rat maternal behavior, which entails complex motivational and social factors, is disrupted by the currently available typical\\u000a and atypical antipsychotics. It is thought that this disruption reflects a side effect of antipsychotics, modeling the neuroleptic-induced\\u000a negative or deficit state. Amisulpiride and aripiprazole are new atypical antipsychotics with mechanisms of action distinct\\u000a from the current typical and atypical antipsychotics. The effects

Ming Li; Radek Budin; Alison S. Fleming; Shitij Kapur



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

Microsoft Academic Search

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

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



Maternal malnutrition during lactation reduces skull growth in weaned rat pups: experimental and morphometric investigation  

Microsoft Academic Search

The purpose of the present study was to evaluate the effects of maternal protein and energy restriction during lactation on\\u000a the bodyweight and skull dimensions of pups at weaning. At parturition, Wistar rat dams were randomly assigned to the following\\u000a groups: (i) control group (C), free access to a standard laboratory diet containing 23% protein; (ii) protein-energy-restricted\\u000a group (PER), free

Rodrigo M. Fernandes; Antonio V. Abreu; Roberto B. Silva; Danielle F. Silva; Gisele L. Martinez; Marcio A. Babinski; Cristiane F. Ramos



Calorimetric and spectroscopic studies characterization of newborn rat’ blood serum after maternal administration of cyclophosphamide  

Microsoft Academic Search

Differential scanning microcalorimetry (DSC) and UV–VIS absorption spectroscopy were used to obtain the characteristics of\\u000a blood serum from newborn rat’ after maternal treatment with cyclophosphamide in comparison with control. The obtained DSC\\u000a curves reveal a complex endothermic peak due to the unfolding process of various serum proteins. Thermal profiles and absorption\\u000a spectra of blood serum are sensitive to the age

Zofia Drzazga; Katarzyna Michalik; Tomasz Halat; Anna Michnik; Henryk I. Trzeciak



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.



Evaluation of Maternal Toxicity in Rats Exposed to Multi-Wall Carbon Nanotubes during Pregnancy  

PubMed Central

Objectives The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

Lim, Jeong-Hyeon; Kim, Sung-Hwan; Lee, In-Chul; Moon, Changjong; Kim, Sung-Ho; Shin, Dong-Ho; Kim, Hyoung-Chin



Impact of experimental diabetes on the maternal uterine vascular remodeling during rat pregnancy.  


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

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



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


Variations in maternal care influence important life history traits that determine reproductive fitness. The adult female offspring of mothers that show reduced levels of pup licking/grooming (LG; i.e., low-LG mothers) show increased defensive responses to stress, accelerated pubertal development, and greater sexual receptivity than the female offspring of high-LG mothers. Amongst several species an accelerated pattern of reproductive development is associated with increased dominance-related behaviors and higher social rank. We hypothesize that rats from low-LG dams may thus also secure higher social rank as a means to compete for limited resources with conspecifics. In this study, social interactions were observed in triads of adult female rats aged p90 that received low, mid, and high levels of pup LG over the first week of life. Low- and mid-LG females had the highest pinning scores and high-LG rats the lowest, showing that low- and mid-LG adult females engage in greater play dominance-related behavior. Likewise, low- and mid-LG rats spent significantly more time drinking following 24?hr of water deprivation in a water competition test thus allowing them to secure a limited resource more easily than high-LG rats. Interestingly, pinning by play dominant females was increased when subordinates were sexually receptive (proestrus/estrus), suggestive of a process of reproductive suppression. Some evidence suggests that low-LG and mid-LG rats also show greater fecundity than high-LG rats. Variations in maternal care may thus have a long-term influence on the development of play dominance and possibly social rank in the female rat, which might contribute to reproductive success within a competitive environment. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 745-756, 2013. PMID:22786820

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



Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain  

PubMed Central

This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life.

Spivey, Jaclyn M.; Padilla, Eimeira; Shumake, Jason D.; Gonzalez-Lima, F.



Impairment of inflammatory response in adult rats submitted to maternal undernutrition during early lactation: Role of insulin and glucocorticoid  

Microsoft Academic Search

Objective: Early nutritional environment may program permanent metabolic alterations, predisposing to later diseases. We have investigated the interference of maternal malnutrition during lactation with the development of acute inflammation in adult rats. Materials and methods: Adult rats, offspring of dams fed with either protein-free diet (UN group) or 22% protein diet (C group) during the first 10 days of lactation,

C. Barja-Fidalgo; E. P. G. Souza; S. V. Silva; A. L. Rodrigues; E. A. Anjos-Valotta; P. Sannomyia; M. S. DeFreitas; A. S. Moura



Effects of neonatal handling and maternal separation on rough-and-tumble play in the rat.  


The extent to which brief daily handling and longer periods of separation from the mother during the first 2 weeks of life can affect play behavior in juvenile rats was assessed. Rat pups were separated from the mother for either 15 min daily (handling) or for 3 hr daily (maternal separation), and play was observed as juveniles. Overall levels of playfulness were not affected by either manipulation, although certain aspects of playful responsiveness were affected in males, but not females. In particular, the pattern of responsiveness to playful contacts was feminized in both handled and separated male rats. Activity in a novel open field at 15 days of age was increased in both males and females from the separated group, but not in the handled animals, as were the number of rears exhibited during the play bouts. These data suggest that early rearing experiences can have subtle gender-dependent effects on some aspects of play in juvenile rats and that the underlying mechanism(s) responsible for these effects may differ from those associated with other effects reported for handling and maternal separation. PMID:12325135

Arnold, Jennifer L; Siviy, Stephen M



In Utero Exposure to Maternal Diabetes Impairs Vascular Expression of Prostacyclin Receptor in Rat Offspring  

PubMed Central

OBJECTIVE To evaluate modifications of arterial structure, gene expression, and function in our model of rats exposed to maternal diabetes. RESEARCH DESIGN AND METHODS Morphometric analyses of elastic vessels structure and determination of thoracic aortic gene expression profile with oligonucleotide chips (Agilent, G4130, 22k) were performed before the onset of established hypertension (3 months). RESULTS Arterial parameters of in situ fixed thoracic aorta were not significantly different between control mother offspring and diabetic mother offspring (DMO). The aortic gene expression profile of DMO is characterized by modifications of several members of the arachidonic acid metabolism including a twofold underexpression of prostacyclin receptor, which could contribute to decreased vasodilatation. This was confirmed by ex vivo experiments on isolated aortic rings. Pharmacological studies on conscious rats showed that systolic blood pressure decline in response to a PGI2 analog was impaired in DMO rats. CONCLUSIONS These results suggest an abnormal vascular fetal programming of prostacyclin receptor in rats exposed in utero to maternal hyperglycemia that is associated with impaired vasodilatation and may be involved in the pathophysiology of hypertension in this model.

Van Huyen, Jean-Paul Duong; Vessieres, Emilie; Perret, Claudine; Troise, Adrien; Prince, Sonia; Guihot, Anne-Laure; Barbry, Pascal; Henrion, Daniel; Bruneval, Patrick; Laurent, Stephane; Lelievre-Pegorier, Martine; Fassot, Celine



Abnormal behavioral and neurotrophic development in the younger sibling receiving less maternal care in a communal nursing paradigm in rats.  


Maternal behavior in rodents has been proposed to vary as a function of the external environment and, in turn, adjust offspring's stress and fear responses. Early handling (brief periods of maternal separation during the first two weeks of life) studies and analyses of spontaneously high-caring rat mothers converge to indicate that increased levels of maternal care may reduce offspring emotionality in adulthood. However, the hypothesis that environment-dependent reduction in maternal care correlates with increased offspring vulnerability to pathology has been scarcely investigated. To test this hypothesis we studied maternal care and offspring development in young, adolescent and young-adult Sprague-Dawley rats reared in a communal nursing situation, characterized by two dams delivering their offspring four days apart and communally caring for them until weaning. We show that dams of the first-born litter show increased aggression towards the pregnant female and that offspring belonging to the second-born litter receive less maternal care compared to older cage-mates. Additionally, second-born rats show increased anxiety-related behavior in a plus-maze test in adolescence and adulthood and abnormal developmental trajectories in terms of social interaction and BDNF levels in the amygdala and hippocampus compared to both the first-born litter and to animal facility reared controls. This is the first indication that adverse environments, not requiring experimenter handling, may reduce maternal care and in turn increase offspring's emotionality and modify social behavior and BDNF developmental trajectories. PMID:19762157

Macrì, Simone; Laviola, Giovanni; Leussis, Melanie P; Andersen, Susan L



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


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

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



Characterization of maternal transfer of decabromodiphenyl ether (BDE-209) administered to pregnant Sprague-Dawley rats.  


To evaluate maternal transfer of decabromodiphenyl ether (BDE-209), Sprague-Dawley rats were given daily oral doses of 5 ?mol/kgb.w. BDE-209 in peanut oil from gestation day (GD) 7 to postpartum day (PD) 4. BDE-209 was increased temporally in maternal blood, placenta, fetuses and neonates. Furthermore, more BDE-209 was found in neonate whole-body samples obtained during lactational period (PD 4) than in that of fetal whole-body samples during pregnancy GD 15 and 21. Overall an increase was observed over time for nona-BDE levels in maternal blood and placenta, but these congeners were decreased in fetuses or neonates. Slight changes were observed for octa-BDEs in both maternal blood and placenta while a significant decrease was observed in the fetuses or neonates for BDE-196 and 198/203. These results demonstrated that BDE-209 and its metabolites can transport to the placenta and milk, and eventually enter the fetuses and/or the neonates. PMID:20851178

Cai, Yunmei; Zhang, Wenbing; Hu, Junjie; Sheng, Guoying; Chen, Dunjin; Fu, Jiamo



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.



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


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



Influence of maternal dietary fat upon rat pups.  


Mother rats were fed purified rations containing different fats during gestation and lactation and at 1 day after parturition. Litter sizes were reduced to 2 male and 2 female pups. The behavior and the brain chemical composition of these selected pups were compared with similarly selected pups from dams fed a commercial ration. All offspring were fed a commercial ration after weaning. Pups from dams fed 20% safflower oil were similar to controls. Feeding 20% cocoa butter to dams resulted in pups with reduced exploratory activity and with a rapid learning performance in a T-maze, employing the aversive stimulation of an electrical shock. Feeding dams a fat-free ration produced pups which had reduced rates of growth, small brains at 2 months of age, and low brain concentrations of cholesterol, DNA, and RNA. PMID:1147334

Borgman, R F; Bursey, R G; Caffrey, B C



Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats  

Microsoft Academic Search

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal\\u000a and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200–220\\u000a g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups\\u000a (control,

Mecit Yoruk; Mehmet Kanter; Ismail Meral; Zahid Agaoglu



Corticosterone synthesis inhibitor metyrapone preserves changes in maternal behavior and neuroendocrine responses during immunological challenge in lactating rats.  


Lactation is associated with profound behavioral and physiological adaptations in the mother that support reproductive success. These include neuroendocrine adaptation to stress that reduces anxiety-related behavior and emotional responsiveness. However, the way in which endogenous glucocorticoids secreted during immunological challenge influence the neuroendocrine system and behavior of lactating rats is not well understood. To evaluate the effects of glucocorticoids on the neuroendocrine response to suckling, maternal behavior and maternal anxiolysis, lactating female rats were treated with vehicle or metyrapone prior to the administration of a saline solution or a lipopolysaccharide (LPS) solution. LPS treatment reduced oxytocin and prolactin secretion during suckling and affected a variety of maternal behaviors, such as increasing the latency of retrieval a new nest, decreasing the number of pups gathered to the nest, increasing the latency of retrieving the first pup and decreasing the percentage of time spent in the arched-nursing position. In addition, the LPS treatment increased the baseline and avoidance latencies in an elevated T-maze. Pretreatment with metyrapone counteracted effects produced by LPS, including hormonal and behavioral responses in lactating rats. Taken together, our results indicate that stress induced by LPS treatment attenuates the neuroendocrine response to suckling, followed by disruption of maternal behavior and maternal anxiolysis in lactating female rats. These changes may be due to corticosterone release, as evidenced by the reversal of behavioral and neuroendocrine responses after immunological challenge in lactating rats that had been pretreated with metyrapone. PMID:23295343

Vilela, Fabiana C; Antunes-Rodrigues, José; Elias, Lucila L K; Giusti-Paiva, Alexandre



Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I. The development of the thyroid hormones–neurotransmitters and adenosinergic system interactions  

Microsoft Academic Search

The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1 to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in

O. M. Ahmed; S. M. Abd El-Tawab; R. G. Ahmed



Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.  


The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. PMID:22173000

Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L



Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats  

PubMed Central

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods.

Ball, Evan R.; Caniglia, Mary Kay; Wilcox, Jenna L.; Overton, Karla A.; Burr, Marra J.; Wolfe, Brady D.; Sanders, Brian J.; Wisniewski, Amy B.; Wrenn, Craige C.



Cognitive, emotional and neurochemical effects of repeated maternal separation in adolescent rats.  


As an adverse early life experience, maternal separation (MS) induces profound neurochemical, cognitive and emotional dysfunction. Previous studies have reported that MS affected prepulse inhibition (PPI), anxiety-related behaviors, dopaminergic and serotonergic activity in adult rats, and in the present study, we investigated the effects of repeated (4h/day) maternal separation during postnatal days 1-21 on PPI and anxiety-related behaviors in an elevated plus maze, as well as dopamine D2 receptor (DRD2) and 5-HT1A receptor expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus in adolescent rats. Our findings show that repeated MS results in reduced PPI, increased anxiety-related behaviors, decreased DRD2 protein expression in the NAc and hippocampus, and decreased 5-HT1A protein expression in the mPFC and hippocampus in adolescent rats. These data further demonstrate that MS can be used as an animal model of neuropsychiatric disease. PMID:23623774

Li, Man; Xue, Xiaofang; Shao, Shuang; Shao, Feng; Wang, Weiwen



A Potential Gastrointestinal Link Between Enhanced Postnatal Maternal Care and Reduced Anxiety-Like Behavior in Adolescent Rats  

Microsoft Academic Search

Early life experience impacts emotional development in the infant. In rat pups, repeated, brief (i.e., 15 min) maternal separation (MS15) during the first 1–2 postnatal weeks has been shown to increase active maternal care and to reduce later anxiety-like behavior in the offspring. We hypothesized that the anxiolytic effect of MS15 is partly due to increased intestinal release of cholecystokinin

Brittany C. Weber; Heather N. Manfredo; Linda Rinaman



Restriction of Maternal Dietary Carbohydrate Decreases Fetal Brain índolesand Glycogen in Rats1«2  

Microsoft Academic Search

In spite of evidence that dietary carbohy drate can increase brain tryptophan and 5-hydroxytryp- tamine in adult rats, the possible influence of maternal dietary carbohydrate on fetal brain Índoles has received little attention. Westudied the effect of graded levels (0, 4, 12 and 60%) of maternal dietary fructose or glucose fed throughout pregnancy on fetal brain glycogen and Índoles. The



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

PubMed Central

Previous research suggests that the maternal medial prefrontal cortex (mPFC) may play a role in maternal care and that cocaine sensitization before pregnancy can affect neuronal activity within this region. The present work was carried out to test whether the mPFC does actually play a role in the expression of maternal behaviors in the rats and to understand what specific behaviors this cortical area may modulate. In the first experiment, tetrodotoxin (TTX) was used to chemically inactivate the mPFC during tests for maternal behavior latencies. Lactating rats were tested on postpartum day 7–9. The results of this first experiment indicate that there is a large effect of TTX-induced inactivation on retrieval behavior latencies. TTX nearly abolished the expression of maternal retrieval of pups without significantly impairing locomotor activity. In the second experiment, GABA-mediated inhibition was used to test maternal behavior latencies and durations of maternal and other behaviors in postpartum dams. In agreement with experiment 1, it was observed that dams capable of retrieving are rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the mPFC largely reduced retrieval without altering other indices of maternal care and non-specific behavior such as ambulation time, self-grooming, and inactivity. Moreover, in both experiments dams were able to establish contact with pups within seconds. The overall results indicate that the mPFC may play an active role in modulating maternal care, particularly retrieval behavior. External factors that affect the function of the frontal cortical site may result in significant impairments in maternal goal-directed behavior as reported in our earlier work.

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



Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation.  


The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index. PMID:19922351

Trujillo, Verónica; Masseroni, María Lujan; Levin, Gloria; Suárez, Marta Magdalena



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

Microsoft Academic Search

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

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



Maternal separation enhances object location memory and prevents exercise-induced MAPK/ERK signalling in adult Sprague-Dawley rats.  


Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague-Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus. PMID:22476924

Makena, Nokuthula; Bugarith, Kishor; Russell, Vivienne A



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


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



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


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

Bourke, Chase H; Neigh, Gretchen N



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

PubMed Central

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

Bourke, Chase H.; Neigh, Gretchen N.



Maternal Antioxidant Supplementation Prevents Adiposity in the Offspring of Western Diet-Fed Rats  

PubMed Central

OBJECTIVE Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. RESEARCH DESIGN AND METHODS Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. RESULTS Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

Sen, Sarbattama; Simmons, Rebecca A.



Dietary protein restriction rapidly reduces transforming growth factor beta 1 expression in experimental glomerulonephritis.  

PubMed Central

Dietary protein restriction has been shown to slow the rate of loss of kidney function in humans with progressive glomerulosclerosis due to glomerulonephritis or diabetes mellitus. A central feature of glomerulosclerosis is the pathological accumulation of extracellular matrix within the diseased glomeruli. Transforming growth factor beta 1 (TGF-beta 1) is known to have widespread regulatory effects on extracellular matrix and has been implicated as a major cause of increased extracellular matrix synthesis and buildup of pathological matrix within glomeruli in experimental glomerulonephritis. In the present study, it is shown that administration of a low protein diet to rats rapidly reduces the elevated expression of TGF-beta 1 mRNA and TGF-beta 1 protein that is known to occur within glomeruli after induction of glomerulonephritis. Compared to a normal protein diet, glomerulonephritic rats receiving the low protein diet did not develop an increase in glomerular extracellular matrix and showed significantly less proteinuria. Glomeruli isolated from glomerulonephritic rats fed the normal protein diet showed a marked increase in proteoglycan synthesis on day 7 of disease and were demonstrated to be secreting increased amounts of TGF-beta 1 into the medium, whereas glomeruli at the same point in time isolated from rats on a low protein diet showed no increase in proteoglycan production or TGF-beta 1 secretion. These results suggest that a mechanism of the rapid therapeutic effect of a low protein diet on experimental glomerulonephritis is through suppression of TGF-beta 1 expression and prevention of the induction of extracellular matrix synthesis within the injured glomeruli. Images

Okuda, S; Nakamura, T; Yamamoto, T; Ruoslahti, E; Border, W A



Maternal condition reduces fear behaviors but not the endocrine response to an emotional threat in virgin female rats.  


Lactating dams and maternal virgin females are less fearful in behavioral tests compared with non-maternal animals, suggesting that maternal condition per se reduces the negative value of threatening stimuli. In addition, lactating females exhibit a diminished hypothalamic-pituitary-adrenal response to potential environmental threats. Can the maternal condition, independently of the endocrine profile of lactation, promote a reduction in the behavioral as well as in the endocrine response to an emotional stressor? To answer this question, anxiety-related and fear behaviors as well as the levels of corticosterone were evaluated in response to a bright-lit open field-loud noise model in maternal and non-maternal non-ovariectomized virgin females and lactating dams in the presence of the pups. Maternal animals, both lactating and virgin, presented an increased exploration of the bright-lit open field and a significant reduction of fear behaviors, indicated by the decreased flight and immobility responses to the subsequent activation of a loud noise, in comparison to non-maternal virgins. Interestingly, maternal virgin females, as non-maternal rats, showed high corticosterone plasma levels, in contrast to the lower endocrine response exhibited by lactating dams when confronted to this threat. Present results suggest that maternal condition allows females to take risks when caring for their young, a behavioral strategy that is independent of the reduced hypothalamic-pituitary-adrenal axis response characteristic of lactation. This evidence points towards a clear dissociation in the mechanisms regulating behavioral and endocrine responses to emotional stressors during motherhood. PMID:18021777

Agrati, D; Zuluaga, M J; Fernández-Guasti, A; Meikle, A; Ferreira, A



Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress.  


Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the (51)CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability. PMID:22155491

Oines, E; Murison, R; Mrdalj, J; Grønli, J; Milde, A M



Maternal exposure to lipopolysaccharide leads to transient motor dysfunction in neonatal rats.  


Epidemiological and experimental data implicate maternal infection and inflammation in the etiology of brain white matter injury, which may lead to cerebral palsy in preterm newborns. Our aim was to investigate motor development of the offspring after maternal administration of lipopolysaccharide (LPS). Wistar rats were intraperitoneally injected with Escherichia coli LPS or saline on gestational days 19 and 20. From birth to 3 weeks, pups were tested for neurobehavioral development, neurological signs and reflexes. From 3 to 6 weeks, motor coordination was investigated. At 4 months, animals were tested for locomotion. Brain myelination was assessed by myelin basic protein immunohistochemistry. Days of appearance of several neurological reflexes were significantly delayed, and neonate LPS pups displayed retarded performance in righting, gait and negative geotaxis. At the juvenile stage, LPS animals showed important impairment in coordination. However, although the LPS group performed worse in most tests, they reached vehicle levels by 5 weeks. At 4 months, LPS animals did not show variations in locomotion performances compared to vehicle. No myelination differences have been observed in the brains at adulthood. Maternal LPS administration results in delayed motor development even though these alterations fade to reach control level by 5 weeks. Motor impairments observed at the early stage in this study could be linked to previously reported hypomyelination of the white matter induced by maternal LPS challenge in the neonates. Finally, the normal myelination shown here at adulthood may explain the functional recovery of the animals and suggest either a potential remyelination of the brain or a delayed myelination in LPS pups. PMID:23445561

Rousset, Catherine I; Kassem, Jinane; Aubert, Arnaud; Planchenault, Deborah; Gressens, Pierre; Chalon, Sylvie; Belzung, Catherine; Saliba, Elie



Maternal exposure to endotoxin delays alveolarization during postnatal rat lung development.  


Maternal bacterial infections adversely affect lung development by crossing the placental barrier and infecting the developing fetus. The underlying mechanism negatively affecting pulmonary development remains unknown. Herein, we investigated whether a systemic maternal infection affects postnatal inflammation and alveolar development. Pregnant rats were injected with 2.5 mg/kg LPS on day 20 and 21 (term = 22 days). Postnatal (PN0-21) mRNA and protein expression of cytokines (IL-1beta, IL-6, IL-10, CXCL1/2, TNFalpha) and genes implicated in alveologenesis [tropoelastin, lysyl oxidase (LOX), lysyl oxidase-like (LOXL)1, tenascin-C (TNC), fibulin 5, vascular endothelial growth factor (VEGF-A), VEGF receptor (VEGFR)2, VEGFR1, platelet-derived growth factor (PDGF)A, PDGFB, and PDGFRalpha] were quantified by real-time PCR and beadlyte technology. Lung transcript and protein levels of IL-1beta, IL-6, and CXCL1/2 were significantly greater in LPS-exposed pups than those of control pups at PN0, 2, 6, 10, and 14. Bronchoalveolar lavage fluid (BALF) of LPS-exposed animals contained significantly more macrophages at PN2 and 14 than BALF of control pups. Morphometric analysis revealed that LPS-exposed animals had fewer and larger alveoli, fewer secondary septa, and decreased peripheral vessel density when compared with control pups. This morphological delay in alveolar development disappeared after PN14. Tropoelastin, LOXL1, VEGF, VEGFR2, and PDGFRalpha mRNA expression of LPS-exposed animals was significantly greater than those of control animals in PN2-14 lungs. TNC, LOX, fibulin 5, VEGFR1, PDGFA, and PDGFB expression was not affected by maternal LPS exposure. Together, the data demonstrate that maternal exposure to endotoxin results in a prolonged pulmonary inflammation postnatally, altered gene expression of molecules implicated in alveologenesis, and delayed morphological maturation of the lung. PMID:19218354

Cao, Lei; Wang, Jinxia; Tseu, Irene; Luo, Daochun; Post, Martin



Embryotoxic effects of brief maternal insulin-hypoglycemia during organogenesis in the rat.  

PubMed Central

To test whether maternal hypoglycemia can impair organogenesis, we induced brief glucopenia with insulin in conscious pregnant rats during either the headfold stage or the early neural tube closure stage of embryogenesis. At each time, 10 pairs of animals received identical insulin infusions for 1 h. Half the animals were maintained at euglycemia during the infusions, while the others were allowed to become hypoglycemic. Euglycemia was maintained or restored in all animals immediately after the insulin was stopped. Spontaneous activity was diminished during the hypoglycemia but consciousness was preserved. Embryos were removed from mothers and examined 2 d later. This examination revealed that embryos from the hypoglycemic mothers were growth-retarded and displayed a small but significant incidence of gross developmental anomalies compared with embryos from the insulin-infused euglycemic mothers. Thus, brief, mild maternal hypoglycemia during early organogenesis can disrupt normal embryo development in the rat. The effect is due to the hypoglycemia per se rather than to the insulin employed for its induction.

Buchanan, T A; Schemmer, J K; Freinkel, N



Fetal growth retardation due to maternal tobacco smoke exposure in the rat.  


Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smoke-exposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6199726

Bassi, J A; Rosso, P; Moessinger, A C; Blanc, W A; James, L S



Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy.  


The purpose of this study was to investigate the influence of parental transgenerational genetics and maternal metabolic state on fetal maldevelopment in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain, and an inbred malformation-prone (L) strain, were cross-mated to produce two different F(1) hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and LW females were mated with normal males of the same F(1) generation to obtain WLWL and LWLW F(2) hybrids. Maternal diabetes increased malformation and resorption rates in both F(2) generations. MD-WLWL offspring had higher resorption rate but similar malformation rate compared with the MD-LWLW offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia, whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft lip and palate. The MD-WL dams showed increased ?-hydroxybutyrate levels and alterations in concentrations of several amino acids (taurine, asparagine, citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene expression of reactive oxygen species (ROS) scavenger enzymes was diminished in MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical autosomal genotypes, the WL and LW dams gave birth to offspring with markedly different malformation patterns. Together with fetal differences in enzymatic activity and expression of Gapdh, ROS scavengers, and developmental genes, these results may suggest a teratological mechanism in diabetic pregnancy influenced by maternal metabolism and parental strain epigenetics. PMID:22374754

Ejdesjö, A; Wentzel, P; Eriksson, U J



Chronic cannabinoid treatment during young adulthood induces sex-specific behavioural deficits in maternally separated rats.  


A combination of early neurodevelopmental disruptions and young-adult cannabis use may lead to the development of neuropsychiatric disorders. The aim of this study was to investigate in adult Wistar rats (12-14 weeks of age) the long-term 'two hit' behavioural effects of chronic young-adult treatment with the cannabinoid receptor agonist, CP55,940 (0.2 mg/kg, 8-10 weeks of age) in combination with maternal separation (MS) (3 h every day from postnatal days 2-14). Two weeks after chronic CP55,940 treatment had ceased, baseline locomotor activity was reduced in male, but not female rats and irrespective of MS. In male rats only, the combination of MS and cannabinoid exposure, but not either 'hit' alone, induced a significant decrease in sucrose preference. In contrast, in male rats both MS and CP55,940 treatment reduced time spent on the open arms of the plus maze or centre time in the open field and this was most pronounced after a combination of these 'hits'. Prepulse inhibition was reduced by MS in both sexes but there was no additional effect of CP55,940 treatment. Memory performance in the Y-maze and novel object recognition test was not affected by either of the two 'hits'. These results indicate that early developmental disruptions and young-adult cannabis use on their own or in combination can differentially and sex-specifically affect behaviours related to neuropsychiatric disorders. PMID:22610052

Klug, Maren; van den Buuse, Maarten



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


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

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



Peripeduncular Nucleus Lesions in the Rat: I. Effects on Maternal Aggression, Lactation, and Maternal Behavior During Pre and Postpartum Periods  

Microsoft Academic Search

Bilateral peripeduncular (PPN) lesions made on the seventh postpartum day (L7) with either radiofrequency (RF) current or N-methyl-d,l-aspartic acid (NMDA)\\/phosphate buffered saline (PBS) reduced maternal aggression (MA) and partially inhibited lactation without producing significant deficits in other items of maternal behavior (MB). RF-PPN lesions did not interfere with prolactin secretion, which suggests that there was deficient oxytocinergic activity. The deficit

Elizabeth M. Factor; Anne D. Mayer; Jay S. Rosenblatt



Periodic Maternal Deprivation Induces Gender-Dependent Alterations in Behavioral and Neuroendocrine Responses to Emotional Stress in Adult Rats  

Microsoft Academic Search

There is evidence that stressful events during the neonatal “stress hyporesponsive period” may influence both emotional behavior and the maturation of the hypothalamic–pituitary–adrenal (HPA) axis in rats. We tested whether periodic maternal deprivation (180 min daily on postnatal days 3–10, PMD) caused chronic changes in emotional behavior and HPA axis activity in either male or female adult rats, or both.

Alexandra Wigger; Inga D Neumann



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


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

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



Role of the brain dopaminergic and opioid system in the regulation of "child's" (maternal bonding) behavior of newborn albino rats.  


Administration of D(2) receptor antagonist clebopride in a dose not affecting locomotor activity was followed by a decrease in maternal bonding behavior of 10-day-old and 15-day-old albino rat pups. D(1) receptor antagonist SCH23390 had a stimulatory effect only on the behavior of 10-day-old newborns. Opioid peptide ?-casomorphin-7 abolished the effect of clebopride in rat pups of the older age group. PMID:21240335

Stovolosov, I S; Dubynin, V A; Kamensky, A A



Maternal-Fetal Transfer of Domoic Acid in Rats at Two Gestational Time Points  

PubMed Central

Background and objectives Prenatal exposure to asymptomatic doses of domoic acid (DA) causes learning and memory deficits later in life; therefore, we sought to measure distribution of DA in maternal plasma and brain, prenatal brain, and amniotic fluid 1 hr after exposure, a time frame that normally encompasses acute seizure behavior. Methods Pregnant rats were given a single intravenous dose of DA (0.6 or 1.6 mg/kg body weight) at either gestational day (GD) 13 or GD20, which correspond to the beginning of rat embryo neurogenesis and the last day of gestation, respectively. Using a direct ELISA, dose-dependent levels of DA were detected in each sample matrix tested. Results An average of 6.6 and 14 ng DA/g brain tissue was found in GD13 and GD20 prenatal rats, respectively. Brain concentrations of DA in the GD13 prenates were identical to amniotic fluid levels, consistent with no restriction for DA to enter the GD13 prenatal brain. At GD20 the prenatal brain contained half the concentration of DA in the amniotic fluid, and was approximately half that found in the brain of the dams. After 1 hr, fetal brain and amniotic fluid contained between 1 and 5% of DA found in the maternal circulation. The amniotic fluid levels of DA in this study were also within the same range measured in stranded California sea lions that showed reproductive failure. Conclusions DA crosses the placenta, enters brain tissue of prenates, and accumulates in the amniotic fluid. Amniotic fluid appears to be a useful fluid to monitor DA exposure.

Maucher, Jennifer M.; Ramsdell, John S.



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


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



Escitalopram improves memory deficits induced by maternal separation in the rat.  


Maternal separation (MS) induces depressive-like behavior and long-term changes in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the depressive-like features caused by this stress model. However, it is not known if it can ameliorate the affected cognition. We now characterized the effect of escitalopram on hippocampal-dependent memory in rats submitted to the MS protocol. Male Wistar rats were assigned either to control (CTR) or maternal separated (MS) group. MS were separated from their dams between 2-14 postnatal days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced swimming test (FST), and memory performance in the Morris water maze (MWM). Escitalopram significantly improved the FST's latency to despair in the MS group (n=6), but did not change the immobility time. All groups showed a significant learning effect in the MWM over time, but no differences have been found upon treatment (n=6). However, escitalopram treatment significantly increased the time spent on the platform quadrant in the probe trial in the MS group. We report here that chronic treatment with escitalopram is able to improve hippocampal dependent memory in a chronic stress model, while not changing the learning ability. Moreover, this is accompanied by an amelioration of the depressive like behavior. These results support the use of escitalopram to tackle underlying cognitive deficits caused by stress in early-life. PMID:22981666

Couto, Frederico Simões do; Batalha, Vânia L; Valadas, Jorge S; Data-Franca, João; Ribeiro, Joaquim A; Lopes, Luísa V



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


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

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



Fetal functional capabilities in response to maternal hypertonicity associated with altered central and peripheral angiotensinogen mRNA in rats  

Microsoft Academic Search

Although a number of studies have shown neural, hormonal, and behavioral capabilities in the control of body fluid regulation under conditions of dehydration in adults, limited information is available on the development of fetal functional abilities in response to osmotic challenge in rats. This study was performed to investigate the influence of maternal hypertonicity on fetal osmoregulatory capabilities at late

Caiping Mao; Juanxiu Lv; Hong Zhu; Yun Zhou; Rongzheng Chen; Xin Feng; Yugui Cui; Chen Wang; Pengpeng Hui; Feichao Xu; Zhice Xu



Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning  

Microsoft Academic Search

In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND)21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and

Sarah J. Borengasser; Franchesca Lau; Ping Kang; Michael L. Blackburn; Martin J. J. Ronis; Thomas M. Badger; Kartik Shankar; Giorgio Sesti



Effects of maternal undernutrition during lactation on aromatase, estrogen, and androgen receptors expression in rat testis at weaning  

Microsoft Academic Search

The goal of this study was to evaluate the effects of maternal malnutrition during lactation on serum levels of testosterone and estradiol, testicular testosterone concentration, aromatase, testicular androgen (AR) and estrogen a (ERa) receptors expression in the pups at weaning. From parturition until weaning, Wistar rats were separated into three groups: (C) control group, with free access to a standard

Cintia Vilanova Teixeira; Dorothee Silandre; Alba Marcelly de Souza Santos; Christelle Delalande; Francisco J B Sampaio; Serge Carreau; Cristiane da Fonte Ramos



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Phenytoin covalent binding and embryopathy in mouse embryos co-cultured with maternal hepatocytes from mouse, rat, and rabbit  

Microsoft Academic Search

The anticonvulsant drug phenytoin is teratogenic in a variety of species including humans. Traditional embryo culture studies have employed the addition of 9000 g supernatant (S-9) or microsomal fractions from induced rat or mouse liver as an exogenous bioactivating system to approximate a maternal contribution. However, cellular fractions, unlike cultured intact hepatocytes, may themselves be embryotoxic, and do not reflect

Terence R. S. Ozolins; Michael J. Wiley; Peter G. Wells



Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition.  


The inhibition of maternal prolactin production in late lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1?mg twice a day) or saline on days 19, 20, and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome and were reversed in the Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma lactate dehydrogenase levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats. PMID:23863192

Boaventura, G; Casimiro-Lopes, G; Pazos-Moura, C C; Oliveira, E; Lisboa, P C; Moura, E G



Maternal separation and proclivity for ethanol intake: a potential role of the endocannabinoid system in rats.  


Maternal separation (MS) during the first postnatal weeks induces alcohol intake and a reduction in the expression of glucocorticoid receptors (GR). Adults' alcohol consumption may depend on changes in the endocannabinoid system (eCBs). Our goal was to evaluate the status of the eCBs before the exposition to alcohol to support the notion that eCBs' alterations prompt rats to drink alcohol. To reach this goal we subjected rats to MS for the first 2 postnatal weeks. Then, we allowed rats to grow with no further manipulation until they reached adulthood. Thereafter, rats were exposed to an alcohol solution (10% of alcohol in water) as the only source of drinking liquid (forced alcohol ingestion). At the end of this period, tap water was added as an option for drinking liquid (voluntary alcohol ingestion) for another 10 days. Different groups of rats (non-MS, and MS) were sacrificed when adult but with no exposition to alcohol whatsoever, to dissect frontal cortex (FCx), ventral striatum (VS) and hippocampus (HIP) to analyze the following: The expression of cannabinoid receptor 1 (CB1R), CB2R, GR and methylated CpG-binding protein 2 (MeCP2). Levels of GABA and glutamate were quantified in the same brain structures. We found CB1 receptor expression increased in the VS while it was decreased in the FCx in MS subjects. No changes in the CB2R or in the MeCP2 were detected. We found GABA levels increased in FCx and HIP but decreased in VS in MS. Likewise, glutamate levels increased in the FCx but decreased in the HIP in MS subjects. These findings suggest that MS induces changes in the CB1R expression, which might contribute to induce a proclivity to ingest alcohol and, potentially, other drugs. PMID:22890080

Romano-López, A; Méndez-Díaz, M; Ruiz-Contreras, A E; Carrisoza, R; Prospéro-García, O



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

PubMed Central

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

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



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


We tested the hypothesis that neonatal maternal separation (NMS), a form of stress that affects hypothalamo-pituitary-adrenal axis (HPA) function in adult rats, alters development of the respiratory control system. Pups subjected to NMS were placed in a temperature and humidity controlled incubator 3 h per day for 10 consecutive days (P3 to P12). Control pups were undisturbed. Once they reached adulthood (8-10 weeks old), rats were placed in a plethysmography chamber for measurement of ventilatory and cardiovascular parameters under normoxic and hypoxic conditions. Measurement of c-fos mRNA expression in the paraventricular nucleus of the hypothalamus (PVH) combined with plasma ACTH and corticosterone levels confirmed that NMS effectively disrupted HPA axis function in males. In males, baseline minute ventilation was not affected by NMS. In contrast, NMS females show a greater resting minute ventilation due to a larger tidal volume. The hypoxic ventilatory response of male NMS rats was 25% greater than controls, owing mainly to an increase in tidal volume response. This augmentation of the hypoxic ventilatory response was sex-specific also because NMS females show an attenuated minute ventilation increase. Baseline mean arterial blood pressure of male NMS rats was 20% higher than controls. NMS-related hypertension was not significant in females. The mechanisms underlying sex-specific disruption of cardio-respiratory control in NMS rats are unknown but may be a consequence of the neuroendocrine disruption associated with NMS. These data indicate that exposure to a non-respiratory stress during early life elicits significant plasticity of these homeostatic functions which persists until adulthood. PMID:14634199

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



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

SciTech Connect

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

Harris, J.E. (Univ. of Kansas, Kansas City (United States))



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

PubMed Central

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

Paternain, Laura; Martisova, Eva; Milagro, Fermin I.; Ramirez, Maria J.; Martinez, J. Alfredo; Campion, Javier



Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat.  


Neonatal maternal separation (NMS) is a form of stress that exerts persistent, sex-specific effects on the hypoxic ventilatory response. Adult male rats previously subjected to NMS show a 25% increase in the response, whereas NMS females show a response 30% lower than controls (8). To assess the extent to which NMS affects ventilatory control development, we tested the hypothesis that NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats. Pups subjected to NMS were placed in a temperature- and humidity-controlled incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography chamber for measurement of ventilatory parameters under baseline and hypercapnic conditions (inspired CO(2) fraction = 0.05). After 20 min of hypercapnia, the minute ventilation response measured in NMS males was 47% less than controls, owing to a lower tidal volume response (22%). Conversely, females previously subjected to NMS showed minute ventilation and tidal volume responses 63 and 18% larger than controls respectively. Although a lower baseline minute ventilation contributes to this effect, the higher minute ventilation/CO(2) production response observed in NMS females suggests a greater responsiveness to CO(2)/H(+) in this group. We conclude that NMS exerts sex-specific effects on the hypercapnic ventilatory response and that the neural mechanisms affected by NMS likely differ from those involved in the hypoxic chemoreflex. PMID:17185497

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



Maternal Di-(2-ethylhexyl)-phthalate Exposure Influences Essential Fatty Acid Homeostasis in Rat Placenta  

PubMed Central

Maintaining essential fatty acid (EFA) homeostasis during pregnancy is critical for fetal development. As the organ that controls the maternal-to-fetal supply of nutrients, the placenta plays a significant role in guiding EFA transfer to the fetus. Many EFA homeostasis proteins are regulated by peroxisome proliferator-activated receptors (PPARs). The metabolites of di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous environmental contaminant, might influence EFA homeostasis via trans-activation of PPARs with subsequent downstream effects on EFA transporters and enzymes. To investigate DEHP’s effect on placental/fetal EFA homeostasis, female Sprague-Dawley rats were orally gavaged with either vehicle or DEHP at 750 or 1500 mg/kg/day from gestational day (GD) 0 to GD 19. Changes in the expression of several EFA homeostasis regulating proteins were determined in the junctional (JXN) and labyrinthine (LAB) zones of the placenta, including PPAR isoforms (?, ? and ?), fatty acid translocase (FAT/CD36), fatty acid transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm), heart cytoplasmic fatty acid binding protein (HFABP), cytochrome P450 (CYP) 4A1, and cyclooxygenase (COX)-1 and -2. Additionally, effects of DEHP maternal exposure on the placental transfer and fetal distribution of representative EFAs, arachidonic acid (AA) and docosahexaenoic acid (DHA), and the placental production of prostaglandins (PGs) were investigated. Expression of PPAR?, PPAR?, FAT/CD36, FATP1, HFABP and CYP4A1 was up-regulated in JXN and/or LAB while COX-2 was down-regulated in JXN. PPAR?, FABPpm, and COX-1 demonstrated variable expression. Reduced directional maternal-to-fetal placental transfer and altered fetal distribution of AA and DHA were observed in concordance with a decreased total placental PG production. These results correlate with previous in vitro data, suggesting that DEHP could influence placental EFA homeostasis with potential downstream effects in the developing fetus.

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



Maternal hypothyroidism decreases progesterone receptor expression in the cortical subplate of foetal rat brain.  


Steroid hormones exert profound effects on the development of brain areas controlling complex cognitive function in adulthood. One class, progestins, may contribute by acting on the progestin receptor (PR), which is transiently expressed in a critical layer of developing cortex: the subplate. PR expression in the subplate coincides with the establishment of ongoing cortical connectivity and may play an important organisational role. Identification of the factor(s) that regulate the precise timing of PR expression within subplate may help elucidate the function of PR. Thyroid hormone may interact with hormone response elements within the PR gene. The present study examined the effects of maternal hypothyroidism on levels of PR immunoreactivity (PR-IR) within the foetal subplate. Pregnant rats were made hypothyroid by the administration of methimazole and potassium perchlorate in drinking water. Maternal hypothyroidism significantly decreased PR-IR within the foetal subplate. Using the incorporation of 5-bromo-2'-deoxyuridine (BrDU) during subplate cell neurogenesis (embryonic day 13.5) to determine subplate cell survival in hypothyroid animals, we found that decreases in PR-IR cannot be attributed to significant subplate cell loss but are more likely the result of altered PR expression. Gestational thyroxine replacement to hypothyroid dams prevented the decrease in PR-IR within the subplate. These results identify thyroid hormone as a potential factor in the regulation of PR expression in the developing brain. These results are consistent with the idea that endocrine cross-talk between progesterone and thyroid hormone may be one mechanism by which maternal hypothyroidism alters normal cortical development. PMID:22435967

Jahagirdar, V; Zoeller, T R; Tighe, D P; Wagner, C K



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

PubMed Central

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

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



Maternal dietary canola oil suppresses growth of mammary carcinogenesis in female rat offspring.  


As suggested by rodent studies and studies using human breast cancer cells, dietary canola oil is linked with lower breast cancer risk. Here, we investigated the effect of maternal (pregnancy plus lactation) dietary canola oil on the susceptibility of female Sprague-Dawley rat offspring to mammary carcinogenesis. Although the control diet had 10% soybean oil, the treatment diet was formulated to contain 10% canola oil as a fat source. N-nitroso-N-methylurea was injected to induce mammary cancer in offspring. The offspring of canola-fed dams showed significantly decreased tumor multiplicity (1.0 ± 0.3 vs. 1.9 ± 0.3, respectively; P = 0.04) and tumor volume (1232.5 ± 771.0 mm(3) vs. 6,302.5 ± 1,747.4 mm(3), respectively; P = 0.01), along with increased survival rate (87% vs. 47%, respectively; P = 0.01). In addition, the mRNA expression of development-related gamma-glutamyltransferase 1 was significantly higher in the lactating mammary tissues of the canola group dams and mammary tumor tissues of the offspring [2.5 ± 0.6 vs. 0.5 ± 0.2, respectively (P = 0.01) and 0.98 ± 0.03 vs. 0.56 ± 0.15, respectively (P = 0.05)]. These results suggest a potential anticancer effect of maternal dietary canola oil and may be useful in devising prenatal nutritional strategies to reduce breast cancer risk in humans. PMID:23859037

Mabasa, Lawrence; Cho, Kyongshin; Walters, Mark W; Bae, Sajin; Park, Chung S



Neonatal maternal separation and early life programming of the hypoxic ventilatory response in rats.  


The neonatal period is critical for central nervous system (CNS) development. Recent studies have shown that this basic neurobiological principle also applies to the neural circuits regulating respiratory activity as exposure to excessive or insufficient chemosensory stimuli during early life can have long-lasting consequences on the performance of this vital system. Although the tactile, olfactory, and auditory stimuli that the mother provides to her offspring during the neonatal period are not directly relevant to respiratory homeostasis, they likely contribute to respiratory control development. This review outlines the rationale for the link between maternal stimuli and programming of the hypoxic ventilatory response during early life, and presents recent results obtained in rats indicating that experimental disruption of mother-pup interaction during this critical period elicits significant phenotypic plasticity of the hypoxic ventilatory response. PMID:15894516

Kinkead, Richard; Genest, Sophie-Emmanuelle; Gulemetova, Roumiana; Lajeunesse, Yves; Laforest, Sylvie; Drolet, Guy; Bairam, Aida



Neonatal maternal separation and neuroendocrine programming of the respiratory control system in rats.  


Neonatal maternal separation (NMS) disrupts central nervous system (CNS) development. Although the consequences of NMS are typically linked with abnormal psychological and behavioural development, there is growing evidence indicating that NMS affects maturation of the respiratory control system. This review discusses results from animal studies in which ventilatory responses to chemical stimuli were measured either in unrestrained rats or in an anesthetised preparation. Data show that NMS interferes with development of ventilatory chemoreflexes in a persistent, sex-specific fashion by affecting both the central and peripheral components of the respiratory control system. NMS likely disrupts the balance between inhibitory (GABAergic) and excitatory modulation within key integrative structures involved in respiratory regulation. Because enhancement of ventilatory chemoreflexes is a hallmark of several cardio-respiratory disorders in humans these results raise important questions concerning the impact of the neonatal of environment on the emergence of respiratory disease related to neural control dysfunction later in life. PMID:19737597

Kinkead, Richard; Gulemetova, Roumiana



Protein restriction in the pregnant mouse modifies fetal growth and pulmonary development: role of fetal exposure to {beta}-hydroxybutyrate.  


Maternal undernutrition during sensitive periods of pregnancy results in offspring predisposed towards the development of a number of diseases of adulthood, including hypertension and diabetes. In order to determine the nature of any gross alterations in fetal growth during early organogenesis, we supplied timed-mated pregnant mice with diets containing 6% protein (6%P), 9% protein (9%P) or 18% protein (18%P; control) from day 0 of pregnancy. At embryonic days 11 (E11), 12 (E12) and 13 (E13), females were killed and fetuses removed. Gross morphological analysis revealed that fetal limb growth was impaired between E11 and E12 in 6%P animals, but this recovered by E13. Likewise, fetal liver growth and lung branching morphogenesis were seen to exhibit an initial growth impairment at E12 followed by a rapid recovery by E13. Coincident with the observed changes in fetal growth, we noted an elevation in maternal hepatic triglyceride content, expression of the ketogenic 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) and circulating plasma ?-hydroxybutyrate (BOHB). In addition, fetal liver Hmgcs2 expression was switched on by E13 in both 6%P- and 9%P-exposed animals. Exogenous BOHB did not influence branching morphogenesis in fetal lung explant cultures; however, we cannot rule out the possibility that this may occur in vivo. In conclusion, we find that disturbance of fetal growth by maternal dietary protein restriction is associated and therefore potentially indicated by changes in maternal and fetal ketone body metabolism. PMID:20851857

Langley-Evans, Simon C; Daniel, Zoe C; Wells, Cathy A; Ryan, Kevin J P; Plant, Richard; Welham, Simon J M



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.

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



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

NASA Astrophysics Data System (ADS)

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

Groziak, Susan Marie


Periodic maternal deprivation and lesion of anterodorsal thalami nuclei induce alteration on hypophyso adrenal system activity in adult rats.  


The hypothalamic-pituitary-adrenal (HPA) axis is normally regulated by extrahypothalamic limbic structures, among these, the anterodorsal thalami nuclei (ADTN), which exert an inhibitory influence on HPA, in basal and acute stress conditions in rats. In the present work we have investigated whether neonatal maternal deprivation (MD) produces long-term changes in the ADTN regulation of HPA activity. Maternal deprivation, in female rats, for 4.5 hs daily, during the first 3 weeks of life, produced at 3 months old, a significant decrease in plasma ACTH concentration (p<0.001) and an increase in plasma corticosterone (C) (p<0.001), compared to control non-deprived rats (NMD). Also MD showed higher plasma epinephrine (E) and norepinephrine (NE) levels than NMD rats. The increase of NE (66.6% p<0.001) was higher than that observed in E (19%). After 30 days of ADTN lesion, plasma ACTH values were higher than in sham lesioned rats, in both NMD and MD animals. ACTH response was greater in MD rats. Plasma C, in NMD, was higher, whereas in MD lesioned animals, it was significantly lower than in sham lesioned. In MD rats, lesion produced a significant increase in plasma E and NE (p<0.001), and again, NE increase was higher than E increase. The more accentuated increase of NE than E, suggests sympathetic nervous system hyperactivity. In summary, neonatal maternal deprivation induces long-term alterations on HPA axis sensitivity and medullo adrenal secretion; enhanced sympathetic nervous system activity and, therefore affected the ADTN inhibitory influence on ACTH and adrenal glands secretion. PMID:11487092

Suárez, M M; Rivarola, M A; Molina, S M; Perassi, N I; Levin, G M; Cabrera, R



Central Infusions of the Recombinant Human Prolactin Receptor Antagonist, S179D-PRL, Delay the Onset of Maternal Behavior in Steroid-Primed, Nulliparous Female Rats  

Microsoft Academic Search

The expression of maternal behavior in the newly parturient rat is under endocrine regulation. Blocking endogenous PRL secretion with bromocriptine delays the normal rapid expression of maternal care shown toward foster young in steroid-primed virgin female rats. The recent development of the PRL receptor antagonist S179D-PRL, a mutant of human PRL in which the serine residue at the 179 position




Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats.  


The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85 mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p<0.001), P8 and P15 (p<0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p<0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p<0.001) and P30 (p<0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. ?-Smooth muscle actin (?-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and ?-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development. PMID:22587910

Capelari, Diego N; Sánchez, Susana I; Ortega, Hugo H; Ciuffo, Gladys M; Fuentes, Lucia B



The effect of protein restriction on the progression of renal insufficiency  

SciTech Connect

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

Ihle, B.U.; Becker, G.J.; Whitworth, J.A.; Charlwood, R.A.; Kincaid-Smith, P.S. (Royal Melbourne Hospital, Victoria (Australia))



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


Changes in lipid metabolism of fetal and maternal rat livers were investigated on day 20 of pregnancy after administration of either 3 mg/kg or 24 mg/kg triamcinolone-acetonide or 124 mg/kg hydrocortisone in crystalline suspension to the mothers on day 15 of pregnancy. Sudan black B and Nile red as well as the UV-Schiff reaction and thin layer chromatography were used to study qualitatively the response of lipids to these glucocorticoids. Generally, after application of triamcinolone-acetonide fetal livers accumulated more lipids as toxic response to this glucocorticoid than the maternal organ; the degree of lipid accumulation was clearly dose-dependent in the fetuses. After hydrocortisone treatment, lipids in maternal livers were slightly, those in the fetuses were not affected. Histochemistry and thin layer chromatography revealed an accumulation of neutral lipids, especially of triglycerides and fatty acids which both contained increased amounts of ethylene bonds after treatment with triamcinolone-acetonide. The results also show that using combined histochemistry and thin layer chromatography, the analysis of hepatic lipids is a promising tool for the assessment of toxic effects of glucocorticoids on fetal and maternal hepatocytes in rats. PMID:2475465

Frank, H G; Gossrau, R; Graf, R



Prenatal transport stress, postnatal maternal behavior, and offspring sex differentially affect seizure susceptibility in young rats.  


Epilepsy is a heterogeneous and chronic neurological condition of undefined etiology in the majority of cases. Similarly, the pathogenesis of the unprovoked seizures that lead to epilepsy is not known. We are interested in the factors that modify inherent seizure susceptibility, with a particular focus on those occurring during the prenatal and early postnatal periods. Female Sprague-Dawley rats were bred in-house or transported during pregnancy at one of two gestational days (G9 or G16). The effects of transport stress, maternal behavior, and offspring sex were then examined in terms of how they were related to provoked seizure susceptibility to kainic acid (KA) or a model of febrile convulsions (FCs) on postnatal day 14 (P14). We also examined the pattern of neuronal activation in the hippocampus and amygdala as indicated by the density of FosB protein immunoreactivity (FosB-ir). Results demonstrated only a small and inconsistent effect of transport alone, suggesting that the groups differed slightly prior to experimental manipulations. However, the influence of maternal behaviors such as licking and grooming (LG), arched back nursing (ABN), and dam-off time (DO) exerted a much stronger effect on the offspring. Dams designated as high LG gave birth to smaller litters, had pups that weighed less, had greater seizure susceptibility and severity, and had more FosB-ir neurons predominantly in the ventral hippocampus and the medial subnucleus of the amygdala (MeA). We also found a sex-dependent effect such that P14 males were smaller than their female littermates and had a greater seizure susceptibility and severity. Taken together, these results suggest an impact of prenatal and postnatal factors, as well as sex, on seizure susceptibility in young animals. PMID:23920381

Moriyama, Chikako; Galic, Michael A; Mychasiuk, Richelle; Pittman, Quentin J; Perrot, Tara S; Currie, R William; Esser, Michael J



[Maternal methyl-containing dietary supplementation alters the ability to learn in adult rats in swimming Morris test].  


Maternal choline diet influences the spatial learning processes. In this work, the learning ability of adult progeny of mothers who had received methyl diet enriched with choline and betain during pregnancy and lactation was studied in Morris test. The introduction of the diet to pregnant rats resulted in an increase in the time of search for invisible platform and time of swimming near the pool walls in offsprings, which meant a worsening of their learning ability. It was also found that change in platform searching strategy was not associated with an increase in anxiety of male rats. Possible involvement of maternal methyl diet in the change of expression of genes which control development of the nervous system is discussed. PMID:16869262

Pliusnina, I Z; Os'kina, I N; Shchepina, O A; Prasolova, L A; Trut, L N


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


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

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



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



Effect of Maternal Dietary Restriction on Fetal Growth and Placental Transfer of «Amino Isobutyric Acid in Rats1  

Microsoft Academic Search

Maternal net weight gain, plasma clearance, and placental and fetal accumulation of I.V. administered 14C-aamino isobutyric acid (AIB)on day 20 of gestation were measured in pregnant rats: 1) fed ad libitum throughout gestation (Control), 2) fed 50% of the normal daily food intake during the last week of gestation (catabolic phase), and 3) fed 50%of the normal daily food intake



Neonatal maternal separation affects endocrine and metabolic stress responses to ether exposure but not to restraint exposure in adult rats  

Microsoft Academic Search

We investigated prolactin secretion and metabolic changes in stress response in adult male rats submitted to periodic maternal\\u000a separation (MS; 180 min\\/day) at 2 weeks of life. Restraint and ether exposure were randomly performed when the animals were\\u000a 10–12 weeks of age. Restraint exposure: the animals were placed into plastic tubes (21 cm long, 4.5 cm diameter) for 20 min.\\u000a Ether exposure: the rats were exposed

Daniela Rocha Costa Fóscolo; Rodrigo Bastos Fóscolo; Umeko Marubayashi; Adelina Martha Reis; Cândido Celso Coimbra



Effect of parental malnutrition on enzyme content of rat pancreas.  


The aim of this study was to assess in rat pups the influence of protein diets ingested by their mothers during gestation and lactation on the enzyme content of the pancreas of the offspring. Rat pups born of either well-nourished mothers or of mothers fed a diet moderately restricted in protein (9% casein w/w) were studied. After weaning, the pups were fed on one of three diets: a well-balanced diet, a 5% casein diet (protein restricted), or a well-balanced diet of a similar caloric value as the protein-restricted diet (pair-fed rat pups). The pups were sacrificed after intervals of one to 25 weeks after weaning. The results showed that the enzyme content of the pancreas increased progressively with time in pups born of malnourished mothers, particularly in pups fed the protein-restricted diet. This suggests prolonged maturation of the pancreas. Pups fed the 5% casein diet had a decreased amylase content per milligram of DNA but not of other enzymes. Malnutrition in the mother increased the ratio of enzymes to DNA and the total pancreatic enzyme content at different times after weaning, indicating that maternal malnutrition had a prolonged effect on the pancreatic enzyme content of the pups' pancreas. This mechanism could play a role in the pathogenesis of tropical chronic calcific pancreatitis in man and explain some of the geographic differences in the incidence of the disease. PMID:2436866

Sarles, H; LaHaie, R; Dollet, J M; Beck, B; Michel, R; Debry, G



Maternal behavior priming in virgin and caesarean-delivered Long-Evans rats: effects of brief contact or continuous exteroceptive pup stimulation.  


The effects of 8 days of prior exposure to pups (Priming) in the form of continuous exteroceptive (smell, sight and sound), or 15 min/day physical access (taste and touch possible) stimulation on the subsequent latency to become maternal during cohabitation with pups (concaveation) was studied in Long-Evans female rats. Brief daily access was effective in hastening the onset of maternal behavior only in those virgins which engaged in pup licking during Priming and in maintaining short-latency maternal responsiveness only in those day 21 pregnancy-terminated, thelectomized rats which initiated maternal behavior during Priming. Exteroceptive stimulation was ineffective in both virgins and caesarean-sectioned rats. These findings stress the importance of physical interactions with pups (unrelated to nipple stimulation) for the development of nurturance. PMID:6665065

Stern, J M



Effects of Maternal Intravenous Nicotine Administration on Locomotor Behavior in Pre-Weanling Rats  

PubMed Central

Maternal tobacco use is associated with adverse developmental outcomes in offspring, including hyperactivity. Animal studies attempting to model this phenomenon have primarily used continuous s.c. nicotine infusion as the method of nicotine administration, which does not model the intermittent bolus delivery of nicotine associated with smoking in humans. The purpose of the present experiment was to examine the locomotor activity of pre-weanling offspring of pregnant rats exposed to an i.v. nicotine dosing protocol that approximates the pattern of nicotine exposure in moderate to heavy smokers. Pregnant rats were administered an i.v. bolus of 0.03 mg/kg nicotine (N=13) or saline (N=10) every 14 min for 16 hr/day, resulting in a total daily dose of 2 mg/kg (base), from gestational day 4 to delivery. Pups from each litter were tested for spontaneous locomotor activity on postnatal days (PND) 19–21 and nicotine-induced locomotor activity on PND 22. Mean birth weight was significantly lower in nicotine-exposed pups compared to controls, but body weights were equivalent between groups by the time of behavioral testing. Mean total distance traveled, vertical counts, and stereotypy counts were lower on PND 19 in nicotine-exposed pups compared to controls, but only the difference in mean stereotypy counts was statistically significant. Within session analysis revealed that both distance traveled and stereotypy were significantly decreased in nicotine-exposed pups in the first five minutes of the session on PND 19. Total time spent in the center of the field was also lower in nicotine exposed pups. Nicotine-induced increases in activity on PND 22 did not differ according to gestational exposure. These findings demonstrate that prenatal nicotine exposure in a model that mimics the pattern of nicotine exposure from cigarette smoking in humans results in offspring that exhibit low birth weight and hypoactivity in a novel environment.

LeSage, Mark G.; Gustaf, Erianne; Dufek, Matthew B.; Pentel, Paul R.



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.

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




EPA Science Inventory

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


Increased Mesohippocampal Dopaminergic Activity and Improved Depression-Like Behaviors in Maternally Separated Rats Following Repeated Fasting/Refeeding Cycles  

PubMed Central

We have previously reported that rats that experienced 3?h of daily maternal separation during the first 2 weeks of birth (MS) showed binge-like eating behaviors with increased activity of the hypothalamic-pituitary-adrenal axis when they were subjected to fasting/refeeding cycles repeatedly. In this study, we have examined the psychoemotional behaviors of MS rats on the fasting/refeeding cycles, together with their brain dopamine levels. Fasting/refeeding cycles normalized the ambulatory activity of MS rats, which was decreased by MS experience. Depression-like behaviors, but not anxiety, by MS experience were improved after fasting/refeeding cycles. Fasting/refeeding cycles did not significantly affect the behavioral scores of nonhandled (NH) control rats. Fasting/refeeding cycles increased dopamine levels not only in the hippocampus but also in the midbrain dopaminergic neurons in MS rats, but not in NH controls. Results demonstrate that fasting/refeeding cycles increase the mesohippocampal dopaminergic activity and improve depression-like behaviors in rats that experienced MS. Together with our previous paper, it is suggested that increased dopamine neurotransmission in the hippocampus may be implicated in the underlying mechanisms by which the fasting/refeeding cycles induce binge-like eating and improve depression-like behaviors in MS rats.

Jahng, Jeong Won; Yoo, Sang Bae; Kim, Jin Young; Kim, Bom-Taeck; Lee, Jong-Ho



Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats.  


Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses. PMID:17553622

Llorente, Ricardo; Arranz, Lorena; Marco, Eva-María; Moreno, Enrique; Puerto, Marta; Guaza, Carmen; De la Fuente, Mónica; Viveros, Maria-Paz



Maternal malnutrition during lactation affects folliculogenesis, gonadotropins, and leptin receptors in adult rats  

Microsoft Academic Search

ObjectiveThe goal of this study was to evaluate if maternal malnutrition during lactation could possibly program folliculogenesis, the ovarian expression of gonadotropins, leptin, and their receptors.

Tatiane da Silva Faria; Flávia de Bittencourt Brasil; Francisco J. B. Sampaio; Cristiane da Fonte Ramos



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


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

Ujházy, E; Mach, M; Dubovický, M; Navarová, J; Soltés, L; Juránek, I; Brucknerová, I; Zeman, M




PubMed Central

Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 21) might affect 7,12-dimethylbenz[a]anthracene (DMBA) -induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-? protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-? protein levels in the lobules and terminal end buds (TEBs). Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the TEBs, lobules or ducts. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was 7-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-? content was causally linked to increased mammary cancer risk among the offspring.

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



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

Microsoft Academic Search

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

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



The effects of postnatal maternal separation on stress responsivity and experimentally induced colitis in adult rats  

Microsoft Academic Search

In this study, we investigated the effects of three neonatal conditions on adult corticosterone (CORT) levels, acoustic startle responses (ASRs), and vulnerability to colitis induced by dextran sulfate sodium (DSS) and how these early manipulations might interact with a brief stress exposure in adulthood on the same measures. Infant animals were subjected daily to either 180-min maternal separation [prolonged maternal

Anne Marita Milde; Øystein Enger; Robert Murison



Effect of maternal excessive iodine intake on neurodevelopment and cognitive function in rat offspring  

PubMed Central

Background Iodine deficiency and iodine excess are both associated with adverse health consequences. Iodine deficiency during pregnancy leads to insufficient maternal thyroid hormone, subsequently causing irreversible adverse effects on the neurological and cognitive functions of the offspring. The results of our previous epidemiological study suggested that mild iodine excess might increase the prevalence of subclinical hypothyroidism. In the present study, female Wistar rats maintained on low-iodine grain were randomly assigned to three groups based on iodated water concentration: low iodine (LI, 1.2??g/d), normal iodine (NI, 5–6??g/d), and 3-fold high iodine (3HI, 15–16??g/d). The present study investigated whether higher-than-normal iodine intake (3HI) by rats from before pregnancy until breastfeeding affects the postnatal (PN) neurodevelopment (PN7 and PN45) of their offspring during particularly sensitive periods in brain development. Results After 12?weeks of treatment (before pregnancy), iodine concentrations in urine and thyroid tissue and circulating thyroxine of adult females correlated with iodine intake. Brain-derived neurotrophic factor (BDNF) expression in the hippocampi of pups on PN7 and PN45 was decreased in 3HI group compared to the NI controls (P??0.05). Results from the Morris water maze test revealed that pups of the 3HI group had mild learning and spatial memory deficits. Conclusions The neurodevelopmental and cognitive deficits of the 3HI pups were mild and temporary, likely related to the changes in hippocampal protein expressions of BDNF and NSP-A.



Maternal deprivation effects on brain plasticity and recognition memory in adolescent male and female rats.  


Data from both human and animal studies suggest that exposure to stressful life events at neonatal stages may increase the risk of psychopathology at adulthood. In particular, early maternal deprivation, 24 h at postnatal day (pnd) 9, has been associated with persistent neurobehavioural changes similar to those present in developmental psychopathologies such as depression and schizophrenic-related disorders. Most neuropsychiatric disorders first appear during adolescence, however, the effects of MD on adolescent animals' brain and behaviour have been scarcely explored. In the present study, we aimed to investigate the emotional and cognitive consequences of MD in adolescent male and female rats, as well as possible underlying neurobiological mechanisms within frontal cortex and hippocampus. Animals were exposed to a battery of behavioural tasks, from pnd 35 to 42, to evaluate cognitive [spontaneous alternation task (SAT) and novel object test (NOT)] and anxiety-related responses [elevated plus maze (EPM)] during adolescence. Changes in neuronal and glial cells, alterations in synaptic plasticity as well as modifications in cannabinoid receptor expression were investigated in a parallel group of control and adolescent (pnd 40) male and female animals. Notably, MD induced a significant impairment in recognition memory exclusively among females. A generalized decrease in NeuN expression was found in MD animals, together with an increase in hippocampal glial fibrillar acidic protein (GFAP) expression exclusively among MD adolescent males. In addition, MD induced in the frontal cortex and hippocampus of male and female adolescent rats a significant reduction in brain derived neurotrophic factor (BDNF) and postsynaptic density (PSD95) levels, together with a decrease in synaptophysin in frontal cortex and neural cell adhesion molecule (NCAM) in hippocampus. MD induced, in animals of both sexes, a significant reduction in CB1R expression, but an increase in CB2R that was statistically significant only for the frontal cortex. Taken together, these results indicate that adolescent females are more vulnerable than males to the cognitive deficits derived from MD despite the changes in neural cells, cannabinoid receptors, as well as the reduction in neural plasticity seem to be similar in both sexes. Further investigation is needed to understand the neurobiological mechanisms underlying the sexual dimorphisms associated to the MD effects, and thus, for a better understanding of the specific sex-dependent vulnerabilities to early life stress. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. PMID:22939999

Marco, Eva M; Valero, Manuel; de la Serna, Oscar; Aisa, Barbara; Borcel, Erika; Ramirez, Maria Javier; Viveros, María-Paz



Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses.  


We previously assessed the motivational properties of pups relative to those of cocaine in parturient female rats (dams) across the postpartum period and demonstrated that the larger subset of dams in early postpartum (PPD8) preferred the pup-associated chamber, whereas the majority of dams tested in late postpartum (PPD16) preferred the cocaine-associated chamber [Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I. 2001. Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav. Neurosci., 115, 683-694; Seip, K.M., Morrell, J.I. 2007. Increasing the incentive salience of cocaine challenges preference for pup- over cocaine-associated stimuli during early postpartum: place preference and locomotor analyses in the lactating female rat. Psychopharmacology 194, 309-319]. The present study uses a dual-choice conditioned place preference to ask how the progression of the postpartum period, including natural pup development, influences maternal motivation for pups. Preferences for cued chambers associated with pups that were age-matched to the postpartum stage of the dam in contrast to a stimulus with little incentive salience were higher during the early than the late postpartum, suggesting that the incentive salience of pups diminishes as the postpartum period progresses. Preferences of the early postpartum dams deprived of pups for 15 min, 2, 6, 12 or 22 hrs prior to conditioning and testing did not differ statistically but there was a trend of more pup preference after 22 hr deprivation; pup age was not an important factor in early postpartum. In marked contrast, late postpartum dams only exhibited robust pup-associated place preference when they were conditioned with young (4-7 day-old) pups or after a 22 hr period of deprivation from contemporaneous pups. Together these results suggest that both forces are at work in the mother-pup dyad, changes in the pups as they develop and changes in the physiological and endocrine state of the female as she progresses through the postpartum period. PMID:18457837

Wansaw, Michael P; Pereira, Mariana; Morrell, Joan I



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



Maternal hypertension induces tissue-specific modulations of the apelinergic system in the fetoplacental unit in rat.  


Apelin and its receptor APJ are expressed in fetal tissues but their function and regulation remain largely unknown. In rat, maternal treatment with a nitric oxide synthase inhibitor inducing hypertension was used to investigate apelin plasma levels in mother/fetus pairs and on the gene expression level of the apelin/APJ system in fetal tissues and placenta. At term, plasma levels of apelin were not modulated but APJ expression was increased in placenta and lung but reduced in heart. Apelin expression was increased only in the heart. We postulate that the apelinergic system may control fetal growth and cardiovascular functions in utero. PMID:22446510

Ivars, Joanna; Butruille, Laura; Knauf, Claude; Bouckenooghe, Thomas; Mayeur, Sylvain; Vieau, Didier; Valet, Philippe; Deruelle, Philippe; Lesage, Jean



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

SciTech Connect

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

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



Optical and X-ray fluorescence spectroscopy studies of bone and teeth in newborn rats after maternal treatment with indinavir.  


An experiment estimating influence of antiviral drug indinavir treatment during pregnancy on bones and teeth development in newborn rats was performed. Two different fluorescence noninvasive spectroscopy techniques, i.e. laser (407 nm)-induced fluorescence method to characterize the organic fluorescent molecules and X-ray fluorescence analysis to determine mineral components were used to study the surface response of femur, mandible and incisor during their formation in the first month of a rat's life. Differences in autofluorescence depending on the form of the bone were observed on the basis of the emission from enamel in 7-, 14- and 28-day-old newborn rats. The dependence between decrease in intensity of fluorescence and increase in mineralization with age in newborn rats was observed. An enhancement of the autofluorescence and a decrease in the concentration of Ca as a main element, as well as disturbances in the concentration of Zn as trace element were observed for bone as well as teeth in newborns during the first month of their life after maternal administration of indinavir (500 mg kg(-1) p.o.) in comparison with the control group. The results indicate that indinavir causes a delay in development of the skeleton and teeth in newborn rats. PMID:19906096

Drzazga, Zofia; Michalik, Katarzyna; Maciejewska, Karina; Kaszuba, Micha?; Nowi?ska, Barbara; Trzeciak, Hanna



Variations in maternal care associated with differences in female rat reproductive behavior in a group-mating environment.  


Maternal care influences the development of sexual behavior in pair mating rats, under laboratory conditions. This study examined the effect of variations in maternal care in a group-mating condition. Groups of two low and two high licking/grooming (LG) female offspring mated with two males in a large pacing chamber for 36?hr. Sexual behaviors were scored for the first 15 vaginal-cervical stimulations (VCS) and the entire 36?hr. Low LG females spent more time mating, required more time to receive an intromission after entering the male compartment. They also received more ejaculations compared to high LG females during the first 15 VCS. This difference disappeared as mating continued. Males were more responsive to high than low females. No pregnancy rate difference was seen between the two female phenotypes, demonstrating that variation in maternal care received results in two mating strategies that are both reproductively successful under group-mating conditions. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 838-848, 2013. PMID:22926834

Prior, Karen M; Meaney, Michael J; Cameron, Nicole M



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

PubMed Central

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

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



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


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



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


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



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))



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))



Neonatal maternal separation enhances phrenic responses to hypoxia and carotid sinus nerve stimulation in the adult anesthetized rat.  


In awake animals, our laboratory recently showed that the hypoxic ventilatory response of adult male (but not female) rats previously subjected to neonatal maternal separation (NMS) is 25% greater than controls (Genest SE, Gulemetova R, Laforest S, Drolet G, and Kinkead R. J Physiol 554: 543-557, 2004). To begin mechanistic investigations of the effects of this neonatal stress on respiratory control development, we tested the hypothesis that, in male rats, NMS enhances central integration of carotid body chemoafferent signals. Experiments were performed on two groups of adult male rats. Pups subjected to NMS were placed in a temperature-controlled incubator 3 h/day from postnatal day 3 to postnatal day 12. Control pups were undisturbed. At adulthood (8-10 wk), rats were anesthetized (urethane; 1.6 g/kg), paralyzed, and ventilated with a hyperoxic gas mixture [inspired O2 fraction (Fi(O2)) = 0.5], and phrenic nerve activity was recorded. The first series of experiments aimed to demonstrate that NMS-related enhancement of the inspiratory motor output (phrenic) response to hypoxia occurs in anesthetized animals also. In this series, rats were exposed to moderate, followed by severe, isocapnic hypoxia (Fi(O2) = 0.12 and 0.08, respectively, 5 min each). NMS enhanced both the frequency and amplitude components of the phrenic response to hypoxia relative to controls, thereby validating the use of this approach. In a second series of experiments, NMS increased the amplitude (but not the frequency) response to unilateral carotid sinus nerve stimulation (stimulation frequency range: 0.5-33 Hz). We conclude that enhancement of central integration of carotid body afferent signal contributes to the larger hypoxic ventilatory response observed in NMS rats. PMID:15790692

Kinkead, Richard; Gulemetova, Roumiana; Bairam, Aida



Maternal infection and fever during late gestation are associated with altered synaptic transmission in the hippocampus of juvenile offspring rats.  


Prenatal exposure to infection is known to affect brain development and has been linked to increased risk for schizophrenia. The goal of this study was to investigate whether maternal infection and associated fever near term disrupts synaptic transmission in the hippocampus of the offspring. We used LPS to mimic bacterial infection and trigger the maternal inflammatory response in near-term rats. LPS was administered to rats on embryonic days 15 and 16 and hippocampal synaptic transmission was evaluated in the offspring on postnatal days 20-25. Only offspring from rats that showed a fever in response to LPS were tested. Schaffer collateral-evoked field excitatory postsynaptic potentials (fEPSPs) and fiber volleys in CA1 of hippocampal slices appeared smaller in offspring from the LPS group compared with controls, but, when the fEPSPs were normalized to the amplitude of fiber volleys, they were larger in the LPS group. In addition, intrinsic excitability of CA1 pyramidal neurons was heightened, as antidromic field responses in the LPS group were greater than those from control. Short-, but not long-term plasticity was impaired since paired-pulse facilitation of the fEPSP was attenuated in the LPS group, whereas no differences in long-term potentiation were noted. These results suggest that LPS-induced inflammation during pregnancy produces in the offspring a reduction in presynaptic input to CA1 with compensatory enhancements in postsynaptic glutamatergic response and pyramidal cell excitability. Neurodevelopmental disruption triggered by prenatal infection can have profound effects on hippocampal synaptic transmission, likely contributing to the memory and cognitive deficits observed in schizophrenia. PMID:18753265

Lowe, Germaine C; Luheshi, Giamal N; Williams, Sylvain



Distal pup cues evoke dopamine responses in hormonally primed rats in the absence of pup experience or ongoing maternal behavior.  


During the early postpartum period or following estrogen/progesterone administration, pups elicit maternal behavior accompanied by a robust dopamine (DA) response in the nucleus accumbens (NAC) of female rats (Afonso et al., 2009). To determine whether DA responds to ostensibly "salient" stimuli in the absence of consummatory behaviors, we examined NAC shell DA responses during restricted (stimuli placed in a perforated box), and unrestricted access to pup and food stimuli. Microdialysis samples were collected from female rats that were either cycling and postpartum (Experiment 1), or after ovariectomy and treated with empty and hormone-filled capsules (Experiment 2). Relative to nonprimed controls, hormonally primed females had suppressed basal DA concentrations and facilitated pup-evoked DA responses, regardless of stimulus access condition. In contrast, food-evoked DA responses were unchanged by hormonal priming and were greater when females consumed food compared with distal (restricted) exposure to food. During pup and food restriction conditions, the lack of any "appetitive" behavioral differences, even in pup experienced postpartum females, was surprising. In Experiment 3, we confirmed that postpartum dams allocated time equivalently to restricted pup and food stimuli, even after pup deprivation. This was in sharp contrast to the effects of deprivation during the unrestricted access phase. Together, our data demonstrated that, in hormonally primed females, distal pup cues could evoke DA responses without prior stimulus experience, ongoing maternal (behavioral) responses, or clear evidence of robust pup saliency. The results suggest that NAC DA response reflects a state of responsiveness related to basal DA suppression in the hormonally primed female rat. PMID:23392661

Afonso, Veronica M; Shams, Waqqas M; Jin, Daniel; Fleming, Alison S



Site and behavioral specificity of periaqueductal gray lesions on postpartum sexual, maternal, and aggressive behaviors in rats.  


Bilateral electrolytic lesions of the lateral and ventrolateral caudal periaqueductal gray (cPAGl,vl) of lactating rats are known to severely reduce suckling-induced kyphosis (upright crouched nursing), which is necessary for maximal litter weight gains, and impair sexual behavior during the postpartum estrous, while heightening nursing in other postures and attacks on unfamiliar adult male intruders. In the present report, the site specificity of the cPAG with respect to the control of these behaviors was determined by comparing lesions of the cPAGl,vl with similarly sized lesions within the rostral PAG (rPAG) and surrounding mesencephalon. The previously seen effects of prepartum cPAGl,vl lesions on kyphotic nursing, sexual proceptivity and receptivity, maternal aggression, and daily litter weight gains were replicated. Additionally, the post-lesion facilitation of aggression was found to be behaviorally specific, first by being directed toward an adult, but not to a nonthreatening juvenile male rat, and second, by requiring the recent presence of the pups, being eliminated or decreased 24 h after removal of the litter. Damage to the rPAG did not affect nursing or sexual behaviors, and had only a minimal effect on maternal aggression. Lesions of the rPAG, however, greatly impaired the dams' ability to rapidly release pups held in the mouth, but not to pick them up or carry them directly to the nest during retrieval. Separate regions of the PAG, therefore, are differentially involved in the control of specific components of behaviors in lactating rats. PMID:9729249

Lonstein, J S; Stern, J M



The newborn rat's stress system readily habituates to repeated and prolonged maternal separation, while continuing to respond to stressors in context dependent fashion.  


Adrenal corticosterone secretion of newborn mice rapidly desensitizes to repeated maternal absence. The present study investigated the effects of novelty exposure, maternal care and genotype on this phenomenon. Maternal separation (MS) took place on postnatal days (pnd) 3-5. In Wistar rats, the degree of novelty in the MS-environment was varied by exposing pups to: (i) "home separation": pups remained in the home cage; (ii) "novel separation": pups were placed individually in a novel cage. Maternal care was recorded on pnd 1 to 4. To investigate the effect of genotype, we also examined Long Evans in the "home separation" condition. Basal and stress-induced ACTH and corticosterone levels were measured. Adrenal tyrosine hydroxylase (TH) and melanocortin receptor-2 (MCR-2) proteins served as markers for adrenal function. We show, in both rat strains, that the rise in plasma corticosterone induced by a single 8h-MS on pnd 5 was abolished, when this separation procedure had also been performed on pnd 3 and 4. Habituation to maternal absence occurred irrespective of housing conditions. However, pups in the "home separation" condition received less maternal care upon reunion than those placed in the "novel separation". These "home separation" pups appeared more responsive to a subsequent acute novelty-stressor, and their adrenal TH and MCR-2 were higher. Long Evans rats appeared more stress responsive than the Wistars, in the home separation condition. In conclusion, separation environment, maternal care and genotype do not affect adrenal desensitization to repeated 8 h-MS itself, but may modulate the adrenal stress-responsiveness of separated pups. PMID:21570400

Daskalakis, Nikolaos P; Claessens, Sanne E F; Laboyrie, Jasper J L; Enthoven, Leo; Oitzl, Melly S; Champagne, Danielle L; de Kloet, E Ronald



High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease  

PubMed Central

Background In earlier studies we found that a high-fat, high-energy diet (HFED) attenuates proteinuria, azotemia and lipid accumulation in the remnant kidney of rats subjected to 5/6 nephrectomy. This study was conducted to explore the mechanism of the salutary effect of HFED in association with moderate protein restriction in this model. Methods The 5/6 nephrectomized male rats were randomized to receive regular rat chow (CRF group, n = 6) or HFED diet (CRF + HFED, n = 7) for 12 weeks. Sham-operated rats served as controls (n = 6). Results The CRF group exhibited azotemia, hypertension, proteinuria, diminished body weight, oxidative stress, glomerulosclerosis, tubulo-interstitial inflammation and upregulation of pro-oxidant [NAD(P)H oxidase], pro-inflammatory (NF-?B activation, increased MCP-1, lipoxygenase, ICAM-1, VCAM-1), pro-fibrotic (TGF-?, CTGF) and pro-apoptotic pathways (Bax, caspase-3) in the remnant kidney. Consumption of the HFED resulted in a 66% increment in lipid intake, 8% increment in carbohydrate intake and a 24% reduction in protein intake. The CRF + HFED group gained weight normally, had increments in leptin and adiponectin levels, and despite increments in plasma cholesterol and fatty acids, showed significant attenuation of oxidative stress, proteinuria and inflammation, and partial reversal of the remnant kidney upregulation of pro-oxidant, pro-inflammatory, pro-fibrotic and pro-apoptotic pathways. Conclusion Consumption of high-energy diet in association with mild protein restriction results in suppression of upregulated pathways that drive progression of renal injury in the remnant kidney model. These findings may have relevance in the management of chronic kidney disease in humans.

Kim, Hyun Ju; Vaziri, Nosratola D.; Norris, Keith; An, Won Suk; Quiroz, Yasmir



Increased responsiveness of presumed 5HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation  

Microsoft Academic Search

Rationale Certain adverse events in childhood, such as loss of a parent or sexual abuse, are associated with an increased vulnerability to develop depression later in life. Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression. Objectives Because dysfunction of brain serotonergic systems has been implicated in the

Lotta Arborelius; Brian W. Hawks; Michael J. Owens; Paul M. Plotsky; Charles B. Nemeroff



Effects in Rats of Maternal Exposure to Raspberry Leaf and Its Constituents on the Activity of Cytochrome P450 Enzymes in the Offspring  

Microsoft Academic Search

The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes

Emilija Makaji; Shirley H. Y. Ho; Alison C. Holloway; Denis J. Crankshaw



Comparison of the effects of maternal protein malnutrition and intrauterine growth restriction on redox state of central nervous system in offspring rats  

Microsoft Academic Search

Both maternal protein malnutrition and intrauterine growth restriction (IUGR) have deleterious effects on brain development, but a comparison of these effects has not been previously reported. The objectives of this study were to investigate and compare the effects of both factors on the oxidative status of the central nervous system (CNS), including the spinal cord, in offspring rats. We evaluated

Mehmet Tatli; Aslan Guzel; Goksel Kizil; Vatan Kavak; Murat Yavuz; Murat Kizil



Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth  

Microsoft Academic Search

Objective:Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from

M J Morris; H Chen




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...


Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver.  


Ethanol is able to cross the placenta, which may cause teratogenicity. Here we investigated whether ethanol consumption during pregnancy (ECDP), even at doses unable to cause malformation, might increase the susceptibility of fetal rat liver to oxidative insults. Since cholestasis is a common condition in alcoholic liver disease and pregnancy, exposure to glycochenodeoxycholic acid (GCDCA) has been used here as the oxidative insult. The mothers received drinking water without or with ethanol from 4 weeks before mating until term, when placenta, maternal liver, and fetal liver were used. Ethanol induced a decreased GSH/GSSG ratio in these organs, together with enhanced gamma-glutamylcysteine synthetase and glutathione reductase activities in both placenta and fetal liver. Lipid peroxidation in placenta and fetal liver was enhanced by ethanol, although it had no effect on caspase-3 activity. Although the basal production of reactive oxygen species (ROS) was higher by fetal (FHs) than by maternal (AHs) hepatocytes in short-term cultures, the production of ROS in response to the presence of varying GCDCA concentrations was higher in AHs and was further increased by ECDP, which was associated to a more marked impairment in mitochondrial function. Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3. In sum, our results indicate that although AHs are more prone than FHs to producing ROS, at doses unable to cause maternal liver damage ethanol consumption causes oxidative stress and apoptosis in fetal liver. PMID:16824660

Perez, Maria J; Velasco, Elena; Monte, Maria J; Gonzalez-Buitrago, Jose M; Marin, Jose J G



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

PubMed Central

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

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



Enhanced Sensitivity to Naltrexone-induced Drinking Suppression of Fluid Intake and Sucrose Consumption in Maternally Separated Rats  

PubMed Central

Early-life stress has been identified as a risk factor in the development of a host of disorders, including substance abuse; however the link between early postnatal stress and changes in measures of reward has not been thoroughly researched. The current study had two main objectives: 1) to determine the impact of maternal separation (an animal model of early-life stress) on the consumption of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female offspring, and 2) to determine the effect of the opioid antagonist naltrexone (0.1 - 3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred for varying lengths of time during the first two postnatal weeks. In experiment 1, a two-bottle choice test (sucrose solution vs. water) was administered across five days to both nonhandled (NH) and maternally-separated (MS) offspring as adults and to dams 2-4 weeks post-weaning. In experiment 2, naltrexone was administered prior to two-bottle choice tests. MS males and the dams of MS litters exhibited increased intake of total fluid and sucrose solutions, whereas results from females were less consistent. Naltrexone elicited a greater decrease in fluid intake and sucrose intake in male MS offspring compared to male NH offspring. These results indicate that early postnatal stress alters both sucrose consumption, a non-drug measure of reward, and apparently the brain opioid systems that mediate naltrexone-induced drinking suppression.

Michaels, Clifford C.; Holtzman, Stephen G



Alteration of pituitary hormone-immunoreactive cell populations in rat offspring after maternal dietary exposure to endocrine-active chemicals.  


We previously performed dose-response studies of genistein, diisononyl phthalate, 4-nonylphenol, methoxychlor (MXC), and bisphenol A to examine the impact of maternal dietary exposure from gestational day 15 to postnatal day 10 on the development of rat reproductive system in later life. Among the chemicals MXC alone showed typical estrogenic effects only at the maternally toxic 1200 ppm. The present study was performed to examine the sensitivity of immunohistochemical analysis of pituitary cells of offspring similarly exposed to each chemical for detection of endocrine-disrupting effects. For this purpose, ratios of pituitary cells expressing luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), were measured at 3 and 11 weeks of age. Ethinylestradiol (EE) at 0.5 ppm was used as a reference chemical. At week 3, decrease in the relative proportions of LH, FSH, and PRL cells in males and LH cells in females was evident with MXC at 1200 ppm. At week 11, increase was found for PRL cells from 240 ppm MXC, and FSH cells at 1200 ppm in females. On the other hand, EE increased the PRL cell percentage in females at week 3 but no effects were apparent at week 11. The other chemicals were without influence at either time point. The results suggest that the assessment of the pituitary cell populations might be a more sensitive approach to detect perinatal endocrine-disrupting effects than other methods. The difference in the pituitary effect between MXC and EE is discussed. PMID:14598022

Masutomi, Naoya; Shibutani, Makoto; Takagi, Hironori; Uneyama, Chikako; Lee, Kyoung-Youl; Hirose, Masao



Maternal hyperthyroidism alters the pattern of expression of cardiac renin-angiotensin system components in rat offspring.  


INTRODUCTION: Changes in perinatal environment can lead to physiological, morphological, or metabolic alterations in adult life. It is well known that thyroid hormones (TH) are critical for the development, growth, and maturation of organs and systems. In addition, TH interact with the renin-angiotensin system (RAS), and both play a critical role in adult cardiovascular function. The objective of this study was to evaluate the effect of maternal hyperthyroidism on cardiac RAS components in pups during development. MATERIALS AND METHODS: From gestational day nine (GD9), pregnant Wistar rats received thyroxine (T4, 12 mg/l in tap water; Hyper group) or vehicle (control group). Dams and pups were killed on GD18 and GD20. RESULTS: Serum concentrations of triiodothyronine (T3) and T4 were higher in the Hyper group than in the control group dams. Cardiac hypertrophy was observed in Hyper pups on GD20. Cardiac angiotensin-converting enzyme (ACE) activity was significantly lower in Hyper pups on both GD18 and GD20, but there was no difference in Ang I/Ang II levels. Ang II receptors expression was higher in the Hyper pup heart on GD18. CONCLUSIONS: Maternal hyperthyroidism is associated with alterations in fetal development and altered pattern of expression in RAS components, which in addition to cardiac hypertrophy observed on GD20 may represent an important predisposing factor to cardiovascular diseases in adult life. PMID:23257210

Lino, Caroline A; Shibata, Caroline Er; Barreto-Chaves, Maria Luiza M



Tonic Pain Response during Inflammation and Stress-Induced Corticosterone Variations in Prenatally Stressed Infant Rats: Effects of Maternal Buspirone Injected during Pregnancy.  


We studied the effects of injections of 5-HT1A-agonist buspirone to pregnant rats before stress exposure on corticosterone level in the dynamics of stress response to inflammatory-induced pain in 7-day-old offspring. During the period of the hypothalamic-pituitary-adrenal system hyporeactivity, the pain response in the formalin test was associated with stress-related corticosterone variations. Maternal buspirone normalized the pain reaction in prenatally stressed rats during all periods of the formalin test and modified the dynamics of the corticosterone response. In 1 day after the formalin test, the basal level of this hormone in blood plasma remained increased. Maternal buspirone increased the resistance of the nociceptive and stress-systems to inflammatory-induced pain response in prenatally stressed rats. PMID:24130987

Butkevich, I P; Mikhailenko, V A; Makukhina, G V; Bagaeva, T R; Stolyarova, Yu A



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.

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



Maternal dietary omega-3 fatty acid supplementation reduces placental oxidative stress and increases fetal and placental growth in the rat.  


Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders including intrauterine growth restriction. Oxidative stress occurs when accumulation of reactive oxygen species damages DNA, proteins, and lipids, an outcome normally limited by antioxidant defenses. Dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may limit oxidative stress by increasing antioxidant capacity, but n-3 PUFAs are also highly susceptible to lipid peroxidation; so n-3 PUFA supplementation is potentially harmful. Here we examined the effect of n-3 PUFAs on placental oxidative stress and on placental and fetal growth in the rat. We also investigated whether diet-induced changes in maternal plasma fatty acid profiles are associated with comparable changes in placental and fetal tissues. Rats were fed either standard or high n-3 PUFA diets from Day 1 of pregnancy, and tissues were collected on Day 17 or 22 (term = Day 23). Dietary supplementation with n-3 PUFAs increased fetal (6%) and placental (12%) weights at Day 22, the latter attributable primarily to growth of the labyrinth zone (LZ). Increased LZ weight was accompanied by reduced LZ F(2)-isoprostanes (by 31% and 11% at Days 17 and 22, respectively), a marker of oxidative damage. Maternal plasma PUFA profiles were altered by dietary fatty acid intake and were strongly predictive of corresponding profiles in placental and fetal tissues. Our data indicate that n-3 PUFA supplementation reduces placental oxidative stress and enhances placental and fetal growth. Moreover, fatty acid profiles in the mother, placenta, and fetus are highly dependent on dietary fatty acid intake. PMID:23269667

Jones, Megan L; Mark, Peter J; Mori, Trevor A; Keelan, Jeffrey A; Waddell, Brendan J



Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat.  


As fetal overexposure to glucocorticoids has been postulated to induce intrauterine growth retardation (IUGR) in humans, we investigated the effects of maternal 50% food restriction (FR50) in rats during the last week of gestation on the hypothalamo-pituitary adrenal (HPA) axis activity in both mothers and their fetuses. In mothers, FR50 increased both the plasma corticosterone (B) level from embryonic days 19-21 and the relative adrenal weight at term. FR50 decreased at term both the maternal plasma corticosteroid-binding globulin level and placental 11beta-hydroxysteroid dehydrogenase type 2 expression. In newborns, maternal FR50 reduced body and adrenal weights, glucocorticoid and mineralocorticoid receptor expressions in the hippocampus, corticoliberin expression in the hypothalamic paraventricular nucleus, and plasma ACTH. In FR50 newborns, the plasma B level was increased at birth and decreased 2 h later. When maternal circulating B was maintained at the basal level by adrenalectomy and B supply, FR50 induced IUGR in pups and decreased placental 11beta- hydroxysteroid dehydrogenase type 2 expression at term, but did not disturb the offspring's HPA axis. These results suggest that maternal undernutrition during late gestation induces both IUGR and an overexposure of fetuses to maternal B, which disturb the development of the HPA axis. PMID:11316731

Lesage, J; Blondeau, B; Grino, M; Bréant, B; Dupouy, J P




PubMed Central

Extracellular single unit activity was recorded from medial prefrontal cortex (mPFC) of postpartum dams over the course of 3 days while they engaged in spontaneous pup-directed behaviors and non-specific exploratory behavior. Out of 109 units identified over the course of the experiment, 15 units were observed to be pup-responsive and 15 increased their discharge rates non-specifically while not attending to pups. An association between neuronal activity and typical maternal behaviors (e.g., retrieval, pup-grooming, nursing) was not observed. Instead, brief bouts of snout contact with pups were accompanied by phasic increases and decreases in spike rates. The observed pup contact responsive cells might play a role in processing of sensory feedback from pups or the transmission of modulatory output to other subcortical maternal brain areas.

Febo, Marcelo



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


Maternal obesity at conception increases the risk of offspring obesity, thus propagating an intergenerational vicious cycle. Male offspring born to obese dams are hyperresponsive to high fat-diets, gaining greater body weight, fat mass, and additional metabolic sequelae compared to lean controls. In this report, we identify the impact of maternal obesity before conception, on the embryo, and intrauterine milieu during the periimplantation period. We conducted global transcriptomic profiling in the uterus and periimplantation blastocyst, gene/protein expression analyses of inflammatory pathways in conjunction with endocrine and metabolic characterization in the dams at implantation. Uterine gene expression profiles of lean and obese dams revealed distinct signatures for genes regulating inflammation and lipid metabolism. Both pathway and gene-set enrichment analysis revealed uterine nuclear factor-?B and c-Jun N-terminal kinase signaling to be up-regulated in the uterus of obese dams, which was confirmed via immunoblotting. Obese uteri also evidenced an inflammatory secretome with higher chemokine mRNA abundance (CCL2, CCL5, CCL7, and CxCL10) and related regulators (TLR2, CD14, and Ccr1). Increased inflammation in the uterus was associated with ectopic lipid accumulation and expression of lipid metabolic genes. Gene expression in sex-identified male periimplantation blastocyst at day postcoitum 4.5 was clearly influenced by maternal obesity (359 transcripts, ±1.4-fold), including changes in developmental and epigenetic regulators. Akin to the uterus, nuclear factor-?B-regulated proinflammatory genes (CCL4 and CCL5) increased and expression of antioxidant (GPx3) and mitochondrial (TFAM and NRF1) genes decreased in the obese embryos. Our results suggest that ectopic lipid and inflammation may link maternal obesity to increased predisposition of offspring to obesity later in life. PMID:21862610

Shankar, Kartik; Zhong, Ying; Kang, Ping; Lau, Franchesca; Blackburn, Michael L; Chen, Jin-Ran; Borengasser, Sarah J; Ronis, Martin J J; Badger, Thomas M



Maternal naltrexone prevents morphological and behavioral alterations induced in rats by prenatal stress  

Microsoft Academic Search

The influence of opioid receptor blockade on the developmental and behavioral effects of prenatal stress was studied. Time-mated dams were implanted with minipumps on day 17 of gestation containing vehicle (V) or naltrexone (NTX, 10 mg\\/kg\\/day). Noise and light stress was applied on an unpredictable basis, three times a week throughout gestation to half the dams. Maternal NTX completely prevented

Gilmore I. Keshet; Marta Weinstock



Paralemniscal TIP39 is induced in rat dams and may participate in maternal functions  

PubMed Central

The paralemniscal area, situated between the pontine reticular formation and the lateral lemniscus in the pontomesencephalic tegmentum contains some tuberoin-fundibular peptide of 39 residues (TIP39)-expressing neurons. In the present study, we measured a 4 times increase in the level of TIP39 mRNA in the paralemniscal area of lactating mothers as opposed to nulliparous females and mothers deprived of pups using real-time RT-PCR. In situ hybridization histochemistry and immunolabeling demonstrated that the induction of TIP39 in mothers takes place within the medial paralemniscal nucleus, a cytoarchitectonically distinct part of the paralemniscal area, and that the increase in TIP39 mRNA levels translates into elevated peptide levels in dams. The paralemniscal area has been implicated in maternal control as well as in pain perception. To establish the function of induced TIP39, we investigated the activation of TIP39 neurons in response to pup exposure as maternal, and formalin injection as noxious stimulus. Both stimuli elicited c-fos expression in the paralemniscal area. Subsequent double labeling demonstrated that 95% of neurons expressing Fos in response to pup exposure also contained TIP39 immunoreactivity and 91% of TIP39 neurons showed c-fos activation by pup exposure. In contrast, formalin-induced Fos does not co-localize with TIP39. Instead, most formalin-activated neurons are situated medial to the TIP39 cell group. Our data indicate that paralemniscal neurons may be involved in the processing of maternal and nociceptive information. However, two different groups of paralemniscal neurons participate in the two functions. In particular, TIP39 neurons may participate in the control of maternal functions.

Varga, Tamas; Mogyorodi, Bence; Bago, Attila G.; Cservenak, Melinda; Domokos, Dominika; Renner, Eva; Gallatz, Katalin; Usdin, Ted B.; Palkovits, Miklos



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

PubMed Central

Objective To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS) and/or restraint stress in adulthood (AS) in Wistar rats. Design Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3×109 CFU/mL) and Propionibacterium jensenii 702 (8.0×108 CFU/mL) from 10 days before conception until postnatal day (PND) 22 (weaning day), or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. Results Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. Conclusion Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the immune environment of stressed animals and protected, in part, against stress-induced disturbances in adult gut microflora.

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




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....


Maternal Experience Produces Long-Lasting Behavioral Modifications in the Rat  

Microsoft Academic Search

From 5 to 22 months of age, cognitive and emotional responses of nulliparous, primiparous, and multiparous rats were assessed using a dry land maze (DLM) and an elevated plus-maze (EPM) at 4-month intervals. Parous rats exhibited improved spatial memory in the probe and competitive versions of the DLM, and more exploration in the EPM and a novel stimulus test relative

Gennifer Love; Nicole Torrey; Ilan McNamara; Melissa Morgan; Margaret Banks; Naomi W. Hester; Erica R. Glasper; A. Courtney DeVries; Craig H. Kinsley; Kelly G. Lambert



Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring  

Microsoft Academic Search

In previous work it has been shown that adult male, but not female, offspring of rats that have either been injected with Prolamine Zinc Insulin on days 15–20 of gestation, or undernourished during the first 2 weeks of gestation, develop significant obesity commencing at about 50 days of age. The present experiment examines the question of whether rats with these

A. P. Jones; E. N. Pothos; P. Rada; D. H. Olster; B. G. Hoebel



Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats.  


The expression of maternal behavior in the newly parturient rat is under endocrine regulation. Blocking endogenous PRL secretion with bromocriptine delays the normal rapid expression of maternal care shown toward foster young in steroid-primed virgin female rats. The recent development of the PRL receptor antagonist S179D-PRL, a mutant of human PRL in which the serine residue at the 179 position is replaced with aspartate, provides a potentially useful tool to examine the role of PRL in neural processing. In the present report, three experiments were conducted that examined the effects of this PRL antagonist on the induction of maternal behavior. In each experiment, ovariectomized, nulliparous rats were treated sequentially with SILASTIC capsules implanted sc with progesterone (days 1-11) and estradiol (days 11-17), a treatment that stimulates a rapid onset of maternal behavior in virgin rats. On day 11, females were implanted with Alzet miniosmotic pumps connected to cannulae directed unilaterally at the lateral ventricle (Exp 1) or bilaterally at the medial preoptic area (MPOA; Exp 2 and 3). Pumps contained either doses of S179D-PRL (0.115 or 1.15 mg/ml; Exp 1 and 2), wild-type human PRL (1.15 mg/ml; Exp 3), or the saline vehicle (Exp 1-3). Testing for maternal behavior began on day 12, a day after pump insertion, and animals were tested daily for 6 days. Latencies to contact, retrieve, and group foster test young were recorded. Administration of both the high and low doses of S179D-PRL infused into the lateral ventricle (Exp 1) or MPOA (Exp 2) significantly delayed the onset of maternal behavior. In contrast, MPOA infusions of the control hormone, wild-type human PRL, in Exp 3 did not delay the onset of maternal behavior. These findings support the concept that the effects of S179D-PRL are caused by its actions as a PRL receptor antagonist rather than by a nonspecific effect of the protein. Overall, these results demonstrate the effectiveness of S179D-PRL acting at the level of the central nervous system (and, more specifically, within the MPOA) to regulate maternal behavior, a PRL-mediated response. PMID:11159845

Bridges, R; Rigero, B; Byrnes, E; Yang, L; Walker, A



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


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

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



Hypercapnic ventilatory response of anesthetized female rats subjected to neonatal maternal separation: insight into the origins of panic attacks?  


Neonatal maternal separation (NMS) is a form of stress that interferes with the regulation of the stress response, an effect that predisposes to the emergence of panic and anxiety related disorders. We previously showed that at adulthood, awake female (but not male) rats subjected to NMS show a hypercapnic ventilatory response (HCVR; 5% CO2) that is 63% greater than controls (Genest et al., 2007). To understand the mechanisms underlying the sex-specific effects of NMS on the ventilatory response to CO2, we used two different anesthetized female rat preparations to assess central CO2 chemosensitivity and contribution of sensory afferents (stretch receptors and peripheral chemoreceptors) that influence the HCVR. Data show that anesthesia eliminated the respiratory phenotype observed previously in awake females and CO2 chemosensitivity did not differ between groups. Finally, the assessment of the ovarian hormone levels across the oestrus cycle failed to reveal significant differences between groups. Since anesthesia did not affect the manifestation of NMS-related respiratory dysfunction in males (including the hypercapnic ventilatory response) (Kinkead et al., 2005; Dumont and Kinkead, 2010), we propose that the panic or anxiety induced by CO2 during wakefulness is responsible for enhancement of the HCVR in NMS females. PMID:21147276

Dumont, Frédéric S; Biancardi, Vivian; Kinkead, Richard




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...


Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats  

PubMed Central

Background Nitric oxide (NO) is implicated in the pathogenesis of irritable bowel syndrome (IBS) but the underlying mechanism is unclear. Thus, the aim of the present study is to examine the role of NO synthase (NOS) expression in the distal colon of neonatal maternal separation (NMS) model rats employed in IBS studies. Methods Male neonates of Sprague-Dawley rats were randomly assigned into NMS and normal control (N) groups. Rats of NMS group were subjected to 3-hr daily maternal separation on postnatal day 2–21. Rats were administrated non-selective NOS inhibitor L-NAME (100mg/kg), selective neuronal NOS (nNOS) inhibitor 7NINA (10mg/kg), selective inducible NOS (iNOS) inhibitor, endothelial NOS (eNOS) inhibitor (10mg/kg) or Vechicle (Veh; distilled water) intraperitoneally 1 hour prior to the experiment for the test and control groups, respectively. Key results The amount of NO was significantly higher in the NMS Veh rats compared with unseparated N rats. Western-blotting and real-time quantitative PCR studies showed that protein and mRNA expression of nNOS were higher in the NMS group than that in the N rats; whereas no significant change in iNOS and eNOS was found in either groups. NMS Veh rats showed low pain threshold and increased electromyogram (EMG) activity in response to colonic distension stimuli. L-NAME and 7NINA increased pain threshold pressure and attenuated EMG activity in the NMS rats. In addition, L-NAME and 7-NINA substantially reduced oxidative marker malondialdehyde level in NMS rats. Conclusions & Inferences NMS increased the NO generation by nNOS upregulation that interact with reactive oxygen species contributing to the visceral hypersensitivity in IBS.

Tjong, Yung-Wui; Ip, Siu-Po; Lao, Lixing; Wu, Justin; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Che, Chun-Tao



Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.  


A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases ?5 desaturase activity but decreases mRNA levels, decreases ?6 desaturase activity but not mRNA levels as compared to control. mRNA level of ?5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver. PMID:22133376

Wadhwani, Nisha S; Manglekar, Rupali R; Dangat, Kamini D; Kulkarni, Asmita V; Joshi, Sadhana R



Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring.  


The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes were prepared from animals at birth (postnatal day 1 [PND1]), weaning (PND21), PND65, and PND120 to determine the biotransformation of 8 fluorogenic substrates. The pattern of biotransformation of all but 2 of the substrates was gender specific. Maternal consumption of RRL increased biotransformation of 3 substrates by female offspring at PND120 resulting in a more masculine profile. Kaempferol and quercetin had a similar effect to RRL. These results suggest that maternal consumption of either RRL or some of its constituents leads to long-term alterations of CYP activity in female offspring. PMID:21115944

Makaji, Emilija; Ho, Shirley H Y; Holloway, Alison C; Crankshaw, Denis J



A gestational low-protein diet represses p21(WAF1/Cip1) expression in the mammary gland of offspring rats through promoter histone modifications.  


Maternal exposure to environmental agents throughout pregnancy may change certain metabolic processes during the offspring's mammary gland development and alter the epigenome. This may predispose the offspring to breast cancer later in life. The purpose of the present study was to examine the effect of maternal protein restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene expression in the mammary gland of rat offspring. Timed-mated Sprague-Dawley rats were fed one of the two isoenergetic diets, control (C, 18 % casein) or low protein (LP, 9 % casein), during gestation. Compared with the C group, LP offspring showed a decrease of p21 in the mammary gland at both the mRNA and protein levels. Chromatin immunoprecipitation assay demonstrated that the down-regulation of p21 transcription in LP offspring was associated with reduced acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter region, but was not associated with acetylation of histone H4 or histone methylation. DNA methylation analysis using bisulphite sequencing did not detect differences in methylation at the p21 promoter between the offspring of the C and LP groups. We conclude that maternal protein restriction inhibits p21 gene expression in the mammary gland of offspring through histone modifications at the promoter region of the p21 gene. PMID:22152918

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



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

PubMed Central

Summary Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target-of-rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP and low calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high, and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions.

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



Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age.  


In this study, we evaluated whether maternal obesity (MO) affects testis development and gonocyte differentiation in the rat from 0.5 to 14.5 postnatal days. Male Wistar rats were used at 0.5, 4.5, 7.5, and 14.5 days post partum (dpp). These rats were born from obese mothers, previously fed with a high-fat diet (20% saturated fat), for 15 weeks, or normal mothers that had received a balanced murine diet (4% lipids). MO did not affect testis weight or histology at birth but changed the migratory behavior of gonocytes. The density of relocated cells was higher in MO pups at 0.5 dpp, decreased at 4.5 dpp, and differed from those of control pups, where density increased exponentially from 0.5 to 7.5 dpp. The numerical density of gonocytes within seminiferous cords did not vary in MO, in relation to control neonates, for any age considered, but the testis weight was 50% lower at 4.5 dpp. A wide variation in plasmatic testosterone and estrogen levels was observed among the groups during the first week of age and MO pups exhibited higher steroid concentrations at 4.5 dpp, in comparison with controls. At this age, higher estrogen levels of MO pups impaired the gonocyte proliferation. At 7.5 dpp, the testicular size and other parameters of gonocyte development are retrieved. In conclusion, MO and saturated lipid diets disturb gonocyte development and sexual steroid levels during the first days of life, with recovery at prepubertal age. PMID:24043845

Christante, Caroline Maria; Taboga, Sebastião Roberto; Pinto-Fochi, Maria Etelvina; Góes, Rejane Maira



Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.  


The non-medical use of prescription opiates, such as Vicodin(®) and MSContin(®), has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females' spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring. PMID:21713113

Johnson, Nicole L; Carini, Lindsay; Schenk, Marian E; Stewart, Michelle; Byrnes, Elizabeth M



Adolescent Opiate Exposure in the Female Rat Induces Subtle Alterations in Maternal Care and Transgenerational Effects on Play Behavior  

PubMed Central

The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal–offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

Johnson, Nicole L.; Carini, Lindsay; Schenk, Marian E.; Stewart, Michelle; Byrnes, Elizabeth M.



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


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

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



Individual Variations in Maternal Care Early in Life Correlate with Later Life Decision-Making and c-Fos Expression in Prefrontal Subregions of Rats  

Microsoft Academic Search

Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology–e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and

Felisa N. van Hasselt; Leonie de Visser; Jacintha M. Tieskens; Sandra Cornelisse; Annemarie M. Baars; Marla Lavrijsen; Harm J. Krugers; Ruud van den Bos; Marian Joëls



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



The set point for maternal glucose homeostasis is lowered during late pregnancy in the rat: the role of the islet beta-cell and liver  

Microsoft Academic Search

Summary  The aim of this study was to determine the effects of late pregnancy on the ability of insulin to suppress maternal hepatic\\u000a glucose production in the rat. Unlike in most previous studies, suppression of hepatic glucose production was measured at\\u000a levels of glycaemia above the relatively hypoglycaemic basal pregnant level. Glucose kinetics were measured using steady-state\\u000a tracer methodology in chronically

C. J. Nolan; J. Proietto



Combined c- fos and 14 C -2-deoxyglucose method to differentiate site-specific excitation from disinhibition: analysis of maternal behavior in the rat  

Microsoft Academic Search

On the basis of evidence that 14C-2-deoxyglucose (2-DG) autoradiography indicates activity at axonal terminals, whereas c-fos immunocytochemistry indicates activity of neuronal cell bodies, we combined these techniques in adjacent histological brain sections to assess excitatory and disinhibitory synaptic relations in selected sites in female rats in which maternal behavior was elicited by natural parturition, sensitization (7- to 10-day cohabitation with

Barry R Komisaruk; Jay S Rosenblatt; Maria Luz Barona; Sandra Chinapen; Jonathan Nissanov; Robert T O'Bannon; Byron M Johnson; Maria Cruz Rodriguez Del Cerro



Maternal deprivation-caused behavioral abnormalities in adult rats relate to a non-methylation-regulated D2 receptor levels in the nucleus accumbens  

Microsoft Academic Search

In this study we investigated the effects of maternal deprivation on adult rats’ spatial learning and memory, exploratory, and limbic activity and their correlations with the gene expression of dopamine transporter (DAT) and dopamine D1, D2, D3 receptors (DRD1, DRD2, DRD3) in the nucleus accumbens (NAc). We further investigated whether DNA methylation is involved in the regulation of DRD2 gene

Xiongzhao Zhu; Ting Li; Sufang Peng; Xiuling Ma; Xiaogang Chen; Xiuwu Zhang



The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care  

Microsoft Academic Search

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,

Nicole M. Cameron; Frances A. Champagne; Carine Parent; Eric W. Fish; Kumi Ozaki-Kuroda; Michael J. Meaney



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

PubMed Central

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

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



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

PubMed Central

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

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



Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction  

Microsoft Academic Search

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control,

Elizabeth A. Levay; Antonio G. Paolini; Antonina Govic; Agnes Hazi; Jim Penman; Stephen Kent



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




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...


Adverse effects of maternal alcohol consumption on pregnancy and foetal growth in rats  

Microsoft Academic Search

JONES et al. have recorded several combined aspects of dysmorphogenesis, severe physical growth retardation and mental deficiency in the human and named it ``foetal alcoholic syndrome'', suggesting the defects to be associated with offspring of chronically alcoholic mothers1. Sandor and Amels2 found that ethanol seemed to produce distinct teratological effects in Wistar rats and chick embryos when it was administered

Wah Jun Tze



Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups  

Microsoft Academic Search

Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. More- over, suckling pups from dams fed a high fat diet had in- creased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) de- ficiency on serum leptin levels in dams and their

M. Korotkova; B. Gabrielsson; L. Å. Hanson; B. Strandvik


Maternal Obesity Induced by Diet in Rats Permanently Influences Central Processes Regulating Food Intake in Offspring  

Microsoft Academic Search

Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin

Shona L. Kirk; Anne-Maj Samuelsson; Marco Argenton; Hannah Dhonye; Theodosis Kalamatianos; Lucilla Poston; Paul D. Taylor; Clive W. Coen; Paul A. Bartell



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


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




Microsoft Academic Search

Female rats maintained on a protein-deficient diet during gestation gave birth to stunted offspring. The progeny, raised on a well balanced diet, grew at a normal rate until the age of twelve to sixteen weeks when their rate of growth became abnormally slow. This slowing down of the rate of growth was associated with an excessive loss of urea, creatinine

Katrine I McLeod; RB Goldrick; HM Whyte



Maternal–fetal Distribution of Manganese in the Rat Following Inhalation Exposure to Manganese Sulfate  

Microsoft Academic Search

Studies examining the pharmacokinetics of manganese during pregnancy have largely focused on the oral route of exposure and have shown that the amount of manganese that crosses the rodent placenta is low. However, limited information exists regarding the distribution of manganese in fetal tissues following inhalation. The objective of this study was to determine manganese body burden in CD rats

David C. Dorman; Anna M. McElveen; Marianne W. Marshall; Carl U. Parkinson; R. Arden James; Melanie F. Struve; Brian A. Wong



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


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

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



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

PubMed Central

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

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



Suppression of retinoic acid receptors may contribute to embryonic skeleton hypoplasia in maternal rats with chronic vitamin A deficiency.  


Vitamin A (VA) is essential for embryonic development and the retinoic acid receptors (RARs) are crucial in mediating the diverse actions of VA in embryogenesis. However, the association between RARs and teratogenicity on skeleton growth and development of vitamin A deficiency (VAD) is not clear. In this present study, weaning female Sprague-Dawley rats were fed purified diets containing graded levels of VA (0, 0.4, 4 IU/g diet) for 70 days before mating, and some of them were supplemented with VA (10 IU/g diet) through pregnancy. Embryos were recovered at embryonic day 19.5 (E19.5) for the analysis of skeleton growth and development and the E12.5 embryos were collected for analysis of select mRNA of RARalpha, RARbeta, RARgamma, Hoxa2, Hoxa5 and Hoxa9. Normal gene expressions and morphogenesis were observed in all embryos from group fed 4 IU/g diet. The embryos from group fed VA-free diet showed a comprehensive suppression of all the genes and general fetal resorption. The embryos from group fed 0.4 IU/g diet exhibited a moderate down-regulation on RARbeta, RARgamma, Hoxa2 and Hoxa5, and the E19.5 fetuses displayed a series of skeletal hypoplasia. The VA supplement groups fed 10 IU/g diet displayed normal gene expressions and morphologic appearances. These findings suggested that the suppression of RARs resulted from VAD could disturb the proper expression of homeobox genes, which might, at least in part, contribute to the embryonic skeletal hypoplasia due to maternal rats with chronic VAD. PMID:19616926

Li, Na; Sun, Shanshan; Wang, Di; Yao, Ping; Yang, Xuefeng; Yan, Hong; Du, Yukai; Ying, Chengjiang; Liu, Liegang



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

PubMed Central

Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring. Preliminary genome-wide analyses of gene transcription and DNA methylation of the molecular basis for such maternal effects suggested differences in the epigenetic state and transcriptional activity of the Grm1 gene in the rat as a function of maternal care. Grm1 encodes the type I metabotropic glutamate receptor (mGluR1), and we found increased mGluR1 mRNA and protein in hippocampus from the adult offspring of mothers showing an increased frequency of pup licking/grooming (i.e., high-LG mothers) that was associated with a decrease in the methylation of Grm1. ChIP assays showed increased levels of histone 3 lysine 9 acetylation and histone 3 lysine 4 trimethylation of Grm1 in hippocampus from the adult offspring of high-LG compared with low-LG mothers. These histone posttranslational modifications were highly correlated, and both associate inversely with DNA methylation and positively with transcription. Studies of mGluR1 function showed increased hippocampal mGluR1-induced long-term depression in the adult offspring of high-LG compared with low-LG mothers, as well as increased paired-pulse depression (PPD). PPD is an inhibitory feedback mechanism that prevents excessive glutamate release during high-frequency stimulation. The maternal effects on both long-term depression and PPD were eliminated by treatment with an mGluR1-selective antagonist. These findings suggest that variations in maternal care can influence hippocampal function and cognitive performance through the epigenetic regulation of genes implicated in glutamatergic synaptic signaling.

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



Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses  

Microsoft Academic Search

We previously assessed the motivational properties of pups relative to those of cocaine in parturient female rats (dams) across the postpartum period and demonstrated that the larger subset of dams in early postpartum (PPD8) preferred the pup-associated chamber, whereas the majority of dams tested in late postpartum (PPD16) preferred the cocaine-associated chamber [Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I.

Michael P. Wansaw; Mariana Pereira; Joan I. Morrell



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



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


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



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


The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness. PMID:9560276

Caldji, C; Tannenbaum, B; Sharma, S; Francis, D; Plotsky, P M; Meaney, M J



Maternal diabetes mellitus and changes in neonatal rat lung and alveolar surfactant phospholipids.  


We investigated the extent of the influence of maternal diabetes on the phospholipid composition and exchange activity of the neonatal lung alveolar surfactant. The results show that each phospholipid fraction (as well as the total phospholipid content) of the surfactant of neonates with diabetic mothers are decreased to about 30% of the control values. Phosphatidylcholine and phosphatidylglycerol, which are the most important surface active phospholipid fractions, were decreased to 27% and 34% respectively. In lung tissue of the neonates with diabetic mothers, all phospholipid fractions were increased. We found that the phosphatidylcholine-exchange activity in the alveolar surfactant does not exist in neonates with diabetic mothers. This inhibited phospholipid-exchange activity may be the reason for the decrease in the surfactant phospholipids and their increase in the lungs of neonates with diabetic mothers. The cholesterol content in the surfactant of such neonates decreased by almost half in comparison with the controls, while in lung tissue it remained unchanged. Producing an experimental respiratory distress syndrome could permit to study more deeply the causes which provoke it and the accompanying metabolic changes. PMID:6688958

Koumanov, K; Boyanov, A; Neicheva, T; Markovska, T; Momchilova, A


Maternal ethanol ingestion: effect on maternal and neonatal glucose balance  

SciTech Connect

Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rate. Female rats were placed on 1) the Lieber-DeCarli liquid ethanol diet, 2) an isocaloric liquid pair-diet, or 3) an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat.

Witek-Janusek, L.



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

PubMed Central

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

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



Assessment of the perinatal effects of maternal ingestion of Solanum malacoxylon in rats.  


A perinatal study was performed to verify the toxic effects of Solanum malacoxylon, which contains a glycoside conjugated to Vitamin D(3). In the gestational study, female rats received S. malacoxylon leaves in the diet at 0, 0.1, 0.2, 0.5, and 1% from days 6 to 21 of pregnancy. At 21 days of gestation, blood samples were taken from the dams for evaluation of serum Ca and P. A laparotomy was performed and the rats were examined for standard parameters of reproductive performance. Fetuses were examined for skeletal changes and histopathologic evaluation. In the second trial, dams were fed diets containing 0 or 0.1% S. malacoxylon leaves during the gestation and lactation periods. After weaning, all animals were euthanized and biochemical and histopathologic evaluations were performed. The biochemical evaluation showed increase in Ca and P levels in females from all experimental groups; however, this effect did not occurred in a dose-related manner. Pups from dams exposed during gestation and lactationi also showed increased Ca and P levels. Fetal data suggested a delay of fetal development manifested by decreased body weight and skeletal alterations. There was also a reduction in live fetuses. Histopathologic study revealed alterations of the soft tissue in litters from dams given 1% dietary S. malacoxylon during pregnancy and 0.1% during pregnancy and lactation. These findings support our hypothesis that Vitamin D(3) glycoside crosses the placenta and suggests milk transfer of this substance. PMID:12507660

Górniak, Silvana Lima; Maiorka, Paulo Cesar; Raspantini, Paulo Cesar; Hosomi, Rosana; Moraes, Ana Paula; Dagli, Maria Lucia Zaidan


Cellular mechanisms underlying failed beta cell regeneration in offspring of protein-restricted pregnant mice.  


Low birth weight and poor foetal growth following low protein (LP) exposure are associated with altered islet development and glucose intolerance in adulthood. Additionally, LP-fed offspring fail to regenerate their ?-cells following depletion with streptozotocin (STZ) in contrast to control-fed offspring that restore ?-cell mass. Our objective was to identify signalling pathways and cellular functions that may be critically altered in LP offspring rendering them susceptible to developing long-term glucose intolerance and decreased ?-cell plasticity. Pregnant Balb/c mice were fed a control (C; 20% protein) or an isocaloric LP (8% protein) diet throughout gestation and C diet thereafter. Female offspring were injected intraperitoneally with 35?mg/kg STZ or vehicle on days 1 to 5 for each dietary treatment. At 30 days of age, total RNA was extracted from pancreatic tissue for microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0. Gene and protein expression were quantified from isolated islets. Finally, ?-cell proliferation was determined in vitro following REG1? treatment. The microarray data and GO enrichment analysis indicated that foetal protein restriction alters the early expression of genes necessary for many cell functions, such as oxidative phosphorylation and free radical scavenging. Expression of Reg1 was upregulated following STZ, whereas protein content was decreased in LP?+?STZ islets. Furthermore, REG1? failed to stimulate ?-cell proliferation in vitro in LP?+?STZ islets. Therefore, early nutritional insults may programme the Reg1 pathway resulting in a limited ability to increase ?-cell mass during metabolic stress. In conclusion, this study implicates the Reg1 pathway in ?-cell regeneration and describes altered programming of gene expression in LP offspring, which underlies later development of cell dysfunction and glucose intolerance in adulthood. PMID:23986224

Cox, Aaron R; Beamish, Christine A; Carter, David E; Arany, Edith J; Hill, David J



2,3,7,8-Tetrachlorodibenzo-p-dioxin in pregnant Long Evans rats: disposition to maternal and embryo/fetal tissues.  


Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with fetal development at doses lower than those causing overt toxicity in adult animals. In a multigeneration study (Murray et al., 1979), female rats that were administered 0.01 microgram TCDD/kg/day in their diet did not experience reduced fertility; however, reduced fertility was seen in the F1 and F2 generations. Exposure to TCDD during development produces alterations in the reproductive system of the developing pups, such as delayed puberty and reduced sperm counts in males (Mably et al., 1992a; Gray et al., 1995) and malformations in the external genitalia of females (Gray and Ostby, 1995). Therefore, the objectives of this study were to determine maternal and fetal tissue concentrations of TCDD that are associated with the adverse reproductive effects seen by Gray and co-workers. Pregnant Long Evans rats received a single oral dose of 1.15 micrograms [3H]TCDD/kg on Gestation Day (GD) 8 and maternal as well as fetal tissue concentrations of TCDD were measured on GD9, GD16, and GD21. On GD9, the highest level of TCDD localized in the maternal liver (25.1% dose). In addition, the amount reaching all the embryos on GD9 was 0.01% of the administered dose, which resulted in a concentration of 0.02% dose/g. The amount of TCDD reaching the fetal compartment (fetuses + placentas) increased to 0.12% dose/tissue on GD16 and 0.71% by GD21. The concentration of TCDD within the fetal compartment (0.01% dose/g) on GD16 was comparable to that found in the maternal blood and spleen. Concentrations of TCDD in a single embryo/fetus were 39.6, 18.1, and 22.1 pg/g on GD9, GD16, and GD21, respectively. Estimates of hepatic half-life of elimination in pregnant rats suggested that TCDD may be eliminated faster in pregnant LE rats. Therefore, measurements of biliary elimination were made in pregnant and nonpregnant LE rats to compare rates of metabolism; however, biliary elimination of TCDD is not affected by pregnancy. In conclusion, this dose administered during a critical period of organogenesis causes adverse effects on the developing reproductive system of rodents. This dose produced a body burden of 22.1 pg TCDD/g within a single fetus on GD21. This indicates that low-level TCDD exposure during the perinatal stage of life can produce adverse effects within the developing pups. PMID:9848119

Hurst, C H; Abbott, B D; DeVito, M J; Birnbaum, L S



Interaction between neonatal allopregnanolone administration and early maternal separation: effects on adolescent and adult behaviors in male rat.  


Endogenous neurosteroid level fluctuations are related to several emotional and behavioral alterations. Neurosteroids also have important roles during neurodevelopment, with there being a relationship between modification of their levels in neurodevelopmental periods and behavioral alterations in adolescence and adulthood. Early maternal separation (EMS) is a stressful event that also alters neurodevelopment and adolescent and adult behaviors. The aim of the present study is to analyze the interaction between the effects of the neonatal alteration of allopregnanolone (AlloP), neurosteroid that increase its levels after acute stress presentation, and EMS on adolescent exploration and adult anxiety and sensorimotor gating in male rats. AlloP (10 mg/kg s.c.) was administrated between postnatal day 5 (PN5) and PN9, and a single 24-hour period of EMS was carried out on PN9. Exploration was analyzed at PN40 and PN60. At adult age (PN85), anxiety was tested by means of the elevated plus-maze test (EPM), and sensorimotor gating by means of prepulse inhibition test (PPI). PPI deterioration has been considered as a reliable indicator of diseases such as schizophrenia. Results showed that the previous neonatal AlloP administration neutralized the effects of EMS in the adolescent exploration (increase of traveled distance and decrease of head-dips). In adult age, an anxiolytic-like profile was observed as a consequence of EMS. Finally, EMS and neonatal AlloP disrupted PPI. Taken together, these data show the important role that physiological neonatal AlloP levels and stressful events play in neural development, adult behavior and vulnerability to neurodevelopmental disorders such as schizophrenia. PMID:23410958

Llidó, Anna; Mòdol, Laura; Darbra, Sònia; Pallarès, Marc



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


Neonatal maternal separation (NMS) affects respiratory control development as adult male (but not female) rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. The paraventricular nucleus of the hypothalamus (PVN) is an important modulator of respiratory activity. In the present study, we hypothesized that in awake rats, altered GABAergic inhibition within the PVN contributes to the enhancement of hypoxic ventilatory response observed in rats previously subjected to NMS. During normoxia, the increase in minute ventilation following microinjection of bicuculline (1 mm) within the PVN is greater in NMS versus control rats. These data show that regulation of ventilatory activity related to tonic inhibition of the PVN is more important in NMS than control rats. Microinjection of GABA or muscimol (1 mM) attenuated the ventilatory response to hypoxia (12% O2) in NMS rats only. The higher efficiency of microinjections in NMS rats is supported by results from GABAA receptor autoradiography which revealed a 22% increase in GABAA receptor binding sites within the PVN of NMS rats versus controls. Despite this increase, however, NMS rats still show a larger hypoxic ventilatory response than controls, suggesting that within the PVN the larger number of GABAA receptors either compensate for (1) a deficient GABAergic modulation, (2) an increase in the efficacy of excitatory inputs converging onto this structure, or (3) both. Together, these results show that the life-long consequences of NMS are far reaching as they can compromise the development of vital homeostatic function in a way that may predispose to respiratory disorders. PMID:17569732

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



Maternal postnatal high-fat diet, rather than gestational diet, affects morphology and mTOR pathway in skeletal muscle of weaning rat.  


The positive regulation of insulin pathway in skeletal muscle results in increased activity of the mammalian target of rapamycin (mTOR), a positive effector of mRNA translation rate and protein synthesis. Studies that assess the activity of this protein in response to chronic high-fat diet (HFD) are scarce and controversial, and to date, there are no studies evaluating the mTOR pathway in infants exposed to gestational and postgestational HFD. This study investigated the effect of maternal HFD on skeletal muscle morphology and on phosphorylation of proteins that comprise the intracellular mTOR signaling pathway in soleus muscle of offspring at weaning. For this purpose, 10 days prior to conception, 39 female Wistar rats were randomly assigned to either control diet (CTL) or HFD. Later, rats were distributed into four groups according to gestational and postpregnancy diet: CTL/CTL (n=10), CTL/HF (n=11), HF/HF (n=10) and HF/CTL (n=8). After 21 days of lactation, pups were killed, and blood samples and soleus and gastrocnemius skeletal muscle were collected for analysis. We observed an influence of maternal postgestational diet, rather than gestational diet, in promoting an obese phenotype, characterized by body fat accumulation, insulin resistance and high serum leptin, glucose, triglycerides and cholesterol levels (P<.05). We have also detected alterations on skeletal muscle morphology--with reduced myofiber density--and impairment on S6 kinase 1 and 4E binding protein-1 phosphorylation (P<.05). These results emphasize the importance of maternal diet during lactation on muscle morphology and on physiological adaptations of infant rats. PMID:23333087

Pantaleão, Lucas C; Teodoro, Gabriela F R; Torres-Leal, Francisco L; Vianna, Daiana; de Paula, Tatyana D; de Matos-Neto, Emídio M; Trindade, Michele C C; Rogero, Marcelo M; Bueno, Carlos R; Tirapegui, Julio



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

PubMed Central

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

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



Sexually dimorphic effects of maternal separation stress on corticotrophin-releasing factor and vasopressin systems in the adult rat brain  

Microsoft Academic Search

Neonatal maternal separation has been widely used to model the well-established causal relationship between stress in early life and the later development of depression. As corticotrophin-releasing factor (CRF) and vasopressin (AVP) have been implicated in depression, we aimed to determine the long-term effects of maternal separation stress on these neuropeptide systems, and also to explore whether these effects are gender-dependent.

Lieve Desbonnet; Lillian Garrett; Emma Daly; Kieran W. McDermott; Timothy G. Dinan



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

PubMed Central

Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system.

Knaepen, Liesbeth; Rayen, Ine; Charlier, Thierry D.; Fillet, Marianne; Houbart, Virginie; van Kleef, Maarten; Steinbusch, Harry W.; Patijn, Jacob; Tibboel, Dick; Joosten, Elbert A.; Pawluski, Jodi L.



Maternal hypoxia increases the susceptibility of adult rat male offspring to high-fat diet-induced nonalcoholic Fatty liver disease.  


Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD. PMID:24002036

Su, Yi-Ming; Lv, Guo-Rong; Xie, Jing-Xian; Wang, Zhen-Hua; Lin, Hui-Tong



Twisted Maternalism  

Microsoft Academic Search

Much of the recent work on Palestinian female suicide bombers (shahidas) explains their violence in domestic and maternal language. These descriptions read shockingly similar to the maternalist position. Maternalism typically equates women's participation in the political arena with peace and non-violence, and is criticized for essentializing women's role. The application of a ‘twisted’ maternalism to women's political violence also appears

Caron E. Gentry



Nerve growth factor-mediated neuronal plasticity in spinal cord contributes to neonatal maternal separation-induced visceral hypersensitivity in rats.  


Visceral hyperalgesia is a multifactorial gastrointestinal disorder which featured with alterations of abdominal motility and/or gut sensitivity, and is believed to be triggered by environmental stressor or psychological factors. However, its etiology remains incompletely understood. In this study, we aimed to investigate whether nerve growth factor (NGF)-mediated neuronal plasticity is involved in neonatal maternal separation (NMS)-induced visceral hypersensitivity in adult rats, and whether NGF antagonist can attenuate or block such development. In our experiments, animals subjected to NMS were developed with visceral hyperalgesia at age of 8 weeks. The threshold for visceral pain among these NMS rats was remarkably lowered than that of the normal handling (NH) rats; however, the expression levels of NGF, c-fos, calcitonin gene-related peptide (CGRP), Substance P, and tyrosine kinases A (TrkA) were notably elevated in lumbosacral spinal cord and/or dorsal root ganglion (DRG) when comparing to those of the NH rats. Further, as intra-peritoneal administration of NGF (10??l at 1??g/kg/day) was given to NH rats during neonatal period, effects that comparable to NMS induction were observed in the adulthood. In contrast, when NMS rats were treated with NGF antagonist K252a (10??l/day from postnatal days 2-14), which acts against tyrosine kinases, the neonatal stress-induced down-shifted visceral pain threshold was restored and neuronal activation, specifically NGF and neuropeptide production, was attenuated. In conclusion, our data strongly suggest that NGF triggers neuronal plasticity and plays a crucial role in NMS-induced visceral hypersensitivity in which NGF antagonism provides positive inhibition via blocking the tyrosine phosphorylation of TrkA. PMID:22396076

Tsang, S W; Zhao, M; Wu, J; Sung, J J Y; Bian, Z-X



The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular steroidogenesis in infantile male rats.  


Exposure of adult male animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases serum androgen concentrations. Reduction in androgen levels after maternal exposure has also been reported, but these results have not been reproduced. We have earlier shown that TCDD stimulates rather than inhibits testosterone synthesis in the prenatal rat testis. The aim of the present study was to elucidate in utero-induced effects of TCDD on testicular steroidogenesis in the 14-day-old infant rats. At that time the foetal Leydig cell population is still the prevailing source of androgens. Pregnant Sprague-Dawley dams were given a single oral dose of TCDD (0, 0.04, 0.2, or 1.0 microg/kg) on day 13 of pregnancy. On postnatal day 14, the body weight of male offspring was reduced after exposure to 1.0 microg/kg TCDD (from 33.9 +/- 1.66 g to 31.6 +/- 2.67 g). Relative testis weight, plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels remained unaltered in all exposure groups. Moreover, in ex vivo incubations, testosterone and cAMP production was not affected. StAR protein level in the freshly isolated testes was increased in the 0.2 microg/kg group, and seminiferous cord diameter in the 0.04 microg/kg group. The present study confirms our earlier findings in in utero TCDD-exposed foetal testis indicating that maternal TCDD exposure does not negatively influence the developmental testosterone production of foetal type Leydig cells in rats. PMID:16533353

Haavisto, T E; Myllymäki, S A; Adamsson, N A; Brokken, L J S; Viluksela, M; Toppari, J; Paranko, J



Neonatal maternal separation enhances dopamine D(2)-receptor and tyrosine hydroxylase mRNA expression levels in carotid body of rats.  


Adult male (but not female) rats previously subjected to neonatal maternal separation (NMS) are hypertensive and show a significant increase (25%) in their hypoxic ventilatory response. To begin investigating the mechanisms involved in this gender-specific disruption in cardiorespiratory regulation, we tested the hypothesis that NMS alters the expression of dopamine D(2)-receptors and tyrosine hydroxylase mRNA in 3 peripheral organs involved in cardio respiratory regulation: the carotid bodies, superior cervical ganglia, and adrenals. Pups subjected to NMS were placed in a temperature- and humidity-controlled incubator 3 h per day for 10 consecutive days (P3-P12). Control pups were undisturbed. Once they reached adulthood (8-10 weeks), male and female rats were anesthetised. The carotid bodies, superior cervical ganglia, and adrenals were harvested for semi-quantitative analyses of dopamine D(2)-receptors and tyrosine hydroxylase mRNA expression using reverse transcription-polymerase chain reaction (carotid bodies only) and Northern blot. In the carotid bodies, comparison of densitometric analyses showed that NMS enhanced tyrosine hydroxylase mRNA expression in male, but not female, rats. Neonatal maternal separation increased dopamine D(2)-receptor mRNA expression also, but the effect was not gender specific. No changes in mRNA expression related to dopaminergic neurotransmission were observed in superior cervical ganglia or the adrenals. These results indicate that subsequent mechanistic investigations should focus on the carotid bodies, as enhancement of dopaminergic neurotransmission within this organ likely contributes to the gender-specific effects of NMS on cardiorespiratory regulation. PMID:15759053

Kinkead, Richard; Joseph, Vincent; Lajeunesse, Yves; Bairam, Aida



Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.  


The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis. PMID:20617189

Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika



A Morphometeric Study on CA3 Hippocampal Field in Young Rats Following Maternal Administration of Boswellia Serrata Resin During Gestation  

Microsoft Academic Search

Objective It has previously been shown that prenatal maternal administration of Boswellia serrata gum resin (Frankincense) improved learning and memory performance associated with an increase in the size of neuronal bodies in CA3 (Cornu Ammonis) of hippocampus. Continuing the previous work, a morphometric study was designed on CA3 field to examine precisely the effect of prenatal administration of frankincense on

Mohamad Hosseini Sharifabad; Ebrahim Esfandiary



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

Microsoft Academic Search

Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint\\/illumination\\/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation

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



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


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



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.



[Maternal phenylketonuria].  


Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently. PMID:23628728

Bókay, János; Kiss, Erika; Simon, Erika; Sz?nyi, László



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

PubMed Central

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

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



Early-life stress affects extinction during critical periods of development: an analysis of the effects of maternal separation on extinction in adolescent rats.  


Adolescence is a period of heightened susceptibility to anxiety disorders, yet we have little experimental evidence on what factors may lead to psychopathology in adolescence. Preclinical models of extinction are commonly used to study the treatment of anxiety symptoms. Interestingly, recent research has shown that there are fundamental changes in the process of extinction across development, which may have implications for our understanding of psychopathology across the lifespan. Specifically, this research shows that the process of extinction parallels the nonlinear function of prefrontal cortex development, such that extinction behaviour is similar in juvenile and adult rats, but involves different processes in infancy and adolescence (periods of rapid growth and pruning, respectively). Our previous studies have shown that early-life stress accelerates the transition between infant and juvenile extinction systems. In the current series of experiments, we examined whether the same early-life stress, maternal separation (MS), would lead to an earlier transition between the juvenile and adolescent extinction systems, and between the adolescent and adult extinction systems. We show that MS adolescent rats exhibit more adult-like extinction behaviour, and that adolescent-like extinction emerges earlier in development (i.e. in pre-adolescent rats). These results may have important implications for the understanding and treatment of anxiety symptoms in adolescent populations. PMID:22356214

Callaghan, Bridget L; Richardson, Rick



Maternal behavior in F344/N and LEW/N rats. Effects on carrageenan-induced inflammatory reactivity and body weight.  


Inbred Fischer (F344/N) and Lewis (LEW/N) rats differ on a myriad of behavioral and physiological endpoints, such as inflammatory, startle and drug responsivity. These differences point to underlying genetic differences between the strains. However, genetic models of hypertension have shown the importance of the maternal environment in the development of high blood pressure, suggesting that maternal influences might also play a role in adult phenotypes of the LEW/N and F344/N strains. This was tested in the present series of experiments in which the effects of crossfostering on carrageenan-induced inflammation and on body weight were examined in the two strains. Following the demonstration that the two strains differed in maternal behavior (Experiment 1), which was independent of the pup being reared (Experiment 2), crossfostered and in-fostered pups from the LEW/N and F344/N strains were injected with carrageenan (at 60 days of age) and subsequently assessed for the accumulation of exudate in response to the injection. Body weights were also monitored from birth through 60 days of age. Although crossfostering affected body weight of the two strains, specifically, reducing weights in LEW/N pups reared by F344/N dams and increasing weights of F344/N pups reared by LEW/N dams, crossfostering did not affect inflammatory reactivity to carrageenan. Specifically, LEW/N pups had a greater level of exudate than F344/N pups, independent of the conditions under which they were reared, suggesting that differences in the inflammatory response between these two strains are under a high degree of genetic control. These results were discussed in terms of genetic factors mediating the early form of immune reactivity induced by carrageenan. PMID:12062314

Gomez-Serrano, Maria A; Sternberg, Esther M; Riley, Anthony L



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:; Tonucci, David A. [Givaudan Flavors Corp., 1199 Edison Drive, Cincinnati, OH 45216 (United States)], E-mail:; 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:; Napoli, Joseph L. [Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA 94720 (United States)], E-mail:; 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:



Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats.  


Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. PMID:22693577

van Hasselt, Felisa N; de Visser, Leonie; Tieskens, Jacintha M; Cornelisse, Sandra; Baars, Annemarie M; Lavrijsen, Marla; Krugers, Harm J; van den Bos, Ruud; Joëls, Marian



Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus axis and improves depression-like behaviors in female rats that experienced neonatal maternal separation.  


This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females. PMID:23010142

Yoo, Sang Bae; Kim, Bom-Taeck; Kim, Jin Young; Ryu, Vitaly; Kang, Dong-Won; Lee, Jong-Ho; Jahng, Jeong Won



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

PubMed Central

Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal “junk-food” diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 g/kg/d; P<0.01). mRNA expression of ?-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.—Ong, Z. Y., Muhlhausler, B. S. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.

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



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

PubMed Central

Exposure to stress during early development causes long-lasting alterations in behavior and hypothalamic pituitary adrenal (HPA) axis activity, including increased expression of corticotropin releasing hormone (CRH). To determine whether early life stress causes epigenetic changes in the CRH promoter leading to increased CRH transcription, 8-week old female and male rats, subjected to maternal deprivation (MD) between days 2 and 13 post-birth, were studied for HPA axis responses to stress and CRH promoter methylation in the hypothalamic paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA). Plasma corticosterone and PVN CRH hnRNA responses to acute restraint stress were higher in MD rats of both sexes. DNA methylation analysis of the CRH promoter revealed a significantly lower percent of methylation in 2 CpGs preceding (CpG1) and inside (CpG2) the cyclic AMP-responsive element (CRE) at ?230 bp in the CRH promoter in the PVN but not the CeA of MD rats. Gel-shift assays, using nuclear proteins from forskolin treated hypothalamic 4B cells and CRH promoter CRE oligonucleotides, unmethylated or methylated at CpG1, revealed a strong band which was supershifted by phospho-CREB antibody. This band was 50% weaker using oligonucleotides methylated at CpG2 (intra-CRE), or methylated at both CpG1 and CpG2. These findings demonstrate that HPA axis hypersensitivity caused by neonatal stress causes long-lasting enhanced CRH transcriptional activity in the PVN of both sexes. Hypomethylation of the CRH promoter CRE, a region critical for CRH transcriptional activation, could serve as a mechanism for the increased transcriptional responses to stress observed in MD rats.

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



Specific effects of maternal zinc depletion or repletion on the deposition of zinc and metallothionein in newborn rat livers: a longitudinal study  

SciTech Connect

High levels of metallothionein (MT) have been reported in association with elevated zinc (Zn) in the livers of newborn rats. Previous studies in this laboratory have demonstrated that maternal Zn-deficiency (Zn-D) specifically reduces the storage of Zn as MT in one day old pup liver. To further investigate how dietary Zn levels influence the storage of Zn as MT, newborn Zn-D pups were allowed to suckle from Zn-sufficient (Zn-S) dams and vice versa. Pups were injected with 2.5 of Zn/sup 65/ and whole body retention monitored. Pups were sacrificed at varying time periods up to weaning and hepatic levels of Zn and MT were measured. A gradual increase in the abnormally low hepatic levels of Zn and MT was observed in Zn-D pups suckling from Zn-S dams up to about day 10. Zn-S pups suckling from Zn-D dams showed a much faster rate of decline of MT and Zn than in age-matched controls, suggesting a rapid turnover of Zn-MT. Whole body retention of Zn/sup 65/ was lower in the Zn-repleted pups than in the pups which were subjected to Zn-D postnatally. These results demonstrate that the Zn-MT levels fluctuate directly in response to the Zn status of the pups, supporting the role of MT as a Zn storage protein in newborn rats.

Gallant, K.R.; Cherian, M.G.



Comparative analysis of maternal care in the high-yawning (HY) and low-yawning (LY) sublines from Sprague-Dawley rats.  


High- and low-yawning rats (HY and LY) were selectively bred as a function of their spontaneous yawning frequency with the LY subline about 2 yawns/hr and the HY 20 yawns/hr. The HY rats have more grooming bouts and travel longer distances in an open field. HY dams spent less time in the nest, retrieved their pups faster, and show a longer latency to licking and mouthing the pups than the LY or outbred Sprague-Dawley (SD) animals. The percentage of HY dams that had atypical retrieving was higher, with a lower nest quality, and produced offspring whose weights were lower than those from the LY subline. We also showed that the pregnant HY dams have fewer pups and the percentage that had lost at least three pups during lactation was higher than the SD and LY dams. In conclusion, HY dams are motivated to take care of their pups, but the "fine tuning" of maternal care is disturbed. PMID:20886537

Ugarte, Araceli; Eguibar, Jose R; Cortés, Ma Del Carmen; León-Chávez, Bertha A; Melo, Angel I



Maternal mortality.  


This article comments on the causes of maternal mortality which are considered preventable if reproductive health services is adequately provided among women belonging to reproductive age. A report from the UN International Children's Emergency Fund announced that 585,000 women die each year from pregnancy and childbirth, which is a 20% increase from the estimates made a decade ago. About 140,000 maternal mortality victims die from violent hemorrhaging, while others perish from blood infections, obstructive deliveries, brain and kidney diseases, and self-administered abortions. It has also been discovered that for every maternal death in childbirth 30 more are grievously wounded. Modest improvements on modern obstetric facilities and proper sanitation and training have been found to dramatically decrease maternal injury and death rates. A foreign aid bill has also been passed to provide a US$600 million fund to address the health issues of both women and children. PMID:12295799



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

PubMed Central

Background The abortifacient claim of Senna alata (S. alata) was scientifically validated recently with alkaloids speculated to be the bioactive agent. This speculation is yet to be substantiated or refuted by scientific evidence. The present study was aimed to investigate the pregnancy terminating effects of the alkaloids from S. alata leaves. Methods Twenty four Pregnant rats (143.99±1.21 g) allocated randomly to four groups: A, B, C and D respectively received, 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the S. alata extracted alkaloids orally, once daily from day 10 until day 18 post-coitum. The indices of abortifacient were evaluated at the end of the exposure period. The results were analyzed by both the analysis of variance and Duncan's multiple range test and p < 0.05 was considered as statistically significant. Results Thin-layer chromatographic separation produced five spots with Rf values of 0.28, 0.33, 0.39, 0.47 and 0.55 which gave positive reaction with Meyer's and Wagner's reagents, respectively. The number of implantation sites and corpora lutea, as well as the concentrations of FSH, LH, progesterone, weight of uterus, uterine/ body weight ratio, glucose and cholesterol decreased significantly (p < 0.05) whereas the resorption index, pre- and post-implantation losses, uterine protein content and alkaline phosphatase activity increased significantly. None of the alkaloid treated animals presented with provoked vaginal opening or bleeding except fetal deaths. The alkaloid decreased the maternal weight gain, as well as feed and water intake. Conclusion Overall, the alkaloids from S. alata leaves exhibited anti-implantation, anti-gonadotropic, anti-progesteronic, embryonic resorptive, feto-maternal toxic activities but not complete abortifacient. The alkaloids alone may not be the sole abortifacient bioactive agent in the leaf extract.

Yakubu, Musa Toyin; Musa, Isa Fakai



Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat.  


We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta. PMID:16282365

Friesen, Russell; Innis, Sheila M



Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats  

Microsoft Academic Search

The activation of extracellular signal-regulated protein kinase (ERK) is essential for pain sensation and development of hyperalgesia\\u000a in chronic pathological pain. Neonatal maternal separation (NMS) could trigger behavioral hyperalgesia and upregulate central\\u000a neuronal activity in rats. The present study aims to investigate whether ERK associates with the colorectal distension (CRD)-evoked\\u000a neuronal response and the upregulated central sensitivity to CRD in

X.-J. Zhang; Z. Li; E. K. Y. Chung; H.-Q. Zhang; H.-X. Xu; J. J. Y. Sung; Z.-X. Bian



Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring  

Microsoft Academic Search

In previous work it has been shown that adult male, but not female, offspring of rats that have been injected with protamine zinc insulin (6 IU\\/kg) on days 15–20 of gestation, develop significant obesity beginning about 50 days of age. This obesity is accompanied by elevated medial hypothalamic extracellular norepinephrine levels. To examine whether the expression of obesity in male

A. P. Jones; D. H. Olster; B. States



Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans  

PubMed Central

Summary Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg ?1 of body weight per day to 0.95 g kg ?1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL ?1 to 152 ng mL ?1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.

Fontana, Luigi; Weiss, Edward P.; Villareal, Dennis T.; Klein, Samuel; Holloszy, John O.



Reversible aberration of neurogenesis affecting late-stage differentiation in the hippocampal dentate gyrus of rat offspring after maternal exposure to manganese chloride.  


To examine the effects of developmental manganese (Mn)-exposure on hippocampal neurogenesis, pregnant rats were treated with MnCl(2)·4H(2)O in the diet at 32, 160 or 800 ppm from gestation day 10 to day 21 after delivery. Serum concentrations of thyroid-related hormones were examined in offspring exposed to MnCl(2)·4H(2)O at 800 or 1600 ppm. Immunohistochemical analysis revealed increased doublecortin-positive cells in the subgranular zone of the dentate gyrus on postnatal day (PND) 21 following exposure to MnCl(2)·4H(2)O at 800 ppm, indicating an increase of type-3 progenitor or immature granule cells. Reelin-positive cells, suggestive of ?-aminobutyric acid-ergic interneurons in the dentate hilus, also increased at 800 ppm on PND 21. Brain Mn concentrations increased in offspring on PND 21 at 160 and 800 ppm, whereas brain concentrations in the dams were unchanged. Serum concentrations of triiodothyronine and thyroxine decreased at 800 and 1600 ppm, whereas thyroid-stimulating hormone increased only after exposure at 800 ppm. All changes disappeared on PND 77. Thus, maternal exposure to MnCl(2)·4H(2)O at 800 ppm mildly and reversibly affects neurogenesis targeting late-stage differentiation in the hippocampal dentate gyrus of rat offspring. Direct effects of accumulated Mn in the developing brain might be implicated in the mechanism of the development of aberrations in neurogenesis; however, indirect effects through thyroid hormone fluctuations might be rather minor. PMID:22561194

Ohishi, Takumi; Wang, Liyun; Akane, Hirotoshi; Shiraki, Ayako; Goto, Ken; Ikarashi, Yoshiaki; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto



Impact of maternal dietary exposure to endocrine-acting chemicals on progesterone receptor expression in microdissected hypothalamic medial preoptic areas of rat offspring.  


We have previously examined the impact of perinatal exposure to ethinylestradiol (EE), methoxychlor (MXC), diisononyl phthalate (DINP), and genistein (GEN) in maternal diet on rat offspring, and found developmental and/or reproductive toxicity with 0.5 ppm EE, 1200 ppm MXC, and 20,000 ppm DINP. Although the toxicological profile with MXC was similar to the EE case, the population changes in pituitary hormone-producing cells totally differed between the two cases, changes being evident from 240 ppm with MXC. In the present study, to assess the impact of these agents on brain sexual differentiation, region-specific mRNA expression of estrogen receptors (ER) alpha and beta, the progesterone receptor (PR), gonadotrophin-releasing hormone, steroid receptor coactivators (SRC)-1 and -2, and calbindin-D in microdissected hypothalamic medial preoptic areas (MPOAs) at postnatal day 10 was first analyzed in rats exposed to 0.5 ppm-EE from gestational day 15 by real-time RT-PCR. Sexually dimorphic expression of ER alpha and PR was noted with predominance in females and males, respectively, EE up-regulating SRC-1 in males and ER beta and PR in females. Next, we similarly examined expression changes of ER alpha and beta, PR, and SRC-1 in animals exposed to MXC at 24, 240, and 1200 ppm, DINP at 4000 and 20,000 ppm, and GEN at 1000 ppm. MXC at 1200 ppm down- and up-regulated PR in males and females, respectively, and DINP at 20,000 ppm down-regulated PR in females, while GEN did not exert any clear effects. The results thus suggest that agents causing developmental and/or reproductive abnormalities in later life may affect hypothalamic PR expression during the exposure period in early life. PMID:16183386

Takagi, Hironori; Shibutani, Makoto; Lee, Kyoung-Youl; Masutomi, Naoya; Fujita, Haruka; Inoue, Kaoru; Mitsumori, Kunitoshi; Hirose, Masao



Effects of a maternal diet supplemented with chocolate and fructose beverage during gestation and lactation on rat dams and their offspring.  


1. Consumption of a high-fat and high-energy diet during pregnancy leads to a risk of long-term consequences on fetal development, as well as on the postnatal health of offspring. To investigate the effects of such a diet on fetal programming, we established a high-energy intake pregnant rat model using chocolate and fructose beverage as supplements to a normal chow diet. 2. Pregnant Sprague-Dawley rats were assigned to either chow (control) or a diet supplemented with chocolate and fructose beverage throughout gestation and lactation. The male F(1) pups received normal chow diet after weaning. Physiological or pathological changes in dams and pups (e.g. glucose and lipid metabolism) were evaluated. 3. The results showed that dams offered the high-fat (mainly from chocolate) and high-calorie diet during gestation consumed more energy and gained more weight than chow-fed dams. Over-consumption of chocolate reduced chow intake in dams, leading to low maternal protein supply. As a result, pups from these dams exhibited reduced birth weight that lasted until adulthood. The high-energy diet during lactation led to increased total body fat, as well as impaired liver function, in offspring; thus, the lactational diet is suggested to be a stronger determinant of offspring fat metabolism than gestational diet. 4. The results of the study suggest that over-supply of carbohydrates, such as chocolate and fructose, either during gestation or lactation has a negative impact on the well-being of offspring. PMID:21722163

Zhang, Zhi-Yun; Zeng, Jin-Jing; Kjaergaard, Marina; Guan, Ni; Raun, Kirsten; Nilsson, Cecilia; Wang, Ming-Wei



Maternal Overweight Induced by a Diet with High Content of Saturated Fat Activates Placental mTOR and eIF2alpha Signaling and Increases Fetal Growth in Rats.  


The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover, mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content, i) up-regulates placental mTOR activity and nutrient transport, resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha); and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high-saturated-fat (HF) diet for 7 wk before mating and during pregnancy. At Gestational Day 21, the HF diet significantly increased maternal and fetal triglyceride, leptin, and insulin (but not glucose) levels and maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher, and phosphorylated rpS6 (S235/236) tended to increase, in the placentas of dams fed an HF diet, indicating an activation of mTOR Complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways, were not altered by the maternal diet. We conclude that maternal overweight induced by an HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth. PMID:24006279

Gaccioli, Francesca; White, Veronica; Capobianco, Evangelina; Powell, Theresa L; Jawerbaum, Alicia; Jansson, Thomas



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

Microsoft Academic Search

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

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



Site and behavioral specificity of periaqueductal gray lesions on postpartum sexual, maternal, and aggressive behaviors in rats  

Microsoft Academic Search

Bilateral electrolytic lesions of the lateral and ventrolateral caudal periaqueductal gray (cPAGl,vl) of lactating rats are known to severely reduce suckling-induced kyphosis (upright crouched nursing), which is necessary for maximal litter weight gains, and impair sexual behavior during the postpartum estrous, while heightening nursing in other postures and attacks on unfamiliar adult male intruders. In the present report, the site

Joseph S. Lonstein; Judith M. Stern



Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats  

Microsoft Academic Search

Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg\\/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3),

Josephine M. Johns; Christina J. Nelson; Kathleen E. Meter; Deborah A. Lubin; C. Destine Couch; Andy Ayers; Cheryl H. Walker



Maternal transfer of 14 C- p,p? - DDT via Placenta and milk and its metabolism in infant rats  

Microsoft Academic Search

Female rats were dosed orally with 0.9 mg14C-ring-labeledp,p?-DDT during pregnancy or lactation. The results from the lactation experiment showed that the mean concentration of14C-DDT in milk was 15.26?g per g dry weight the first day after dosing, and decreased gradually with a rate constant of clearance of ?0.096. The half-life of DDT and its metabolites in milk was approximately 7.2

S. C. Fang; Elizabeth Fallin; V. H. Freed



Influence of pregnancy and lactation on maternal deposition and perinatal uptake of 241Am in the rat.  


To investigate the metabolism of 241Am as affected by pregnancy and lactation, female rats were injected with 5 muCi of 241Am intravenously while nulliparous, pregnant or lactating. The females and subsequent litters were killed at various times after injection to determine 241Am distribution and retention. The temporal relationship between injection and pregnancy influenced the tissue retention of 241Am in both dams and progeny. The half-time of 241Am in livers of pregnant or lactating rats was more than twice that of nulliparous rats, although the initial uptake was approximately 50% of the activity in all groups. Both spleen and femur accumulated more 241Am at 7-10 weeks after injection than at earlier times, but this increase could not be related to pregnancy. Approximately 10 times more 241Am was transferred to offspring from dams that were lactating when exposed than was transferred via the placenta when exposure occurred late in gestation. Furthermore, more 241Am was transmitted to the progeny via milk if exposure of the dam occurred during lactation rather than during pregnancy. PMID:3700111

Sasser, L B; Mahlum, D D; Rommereim, R L



Influence of pregnancy and lactation on maternal deposition and perinatal uptake of /sup 241/Am in the rat  

SciTech Connect

To investigate the metabolism of /sup 241/Am as affected by pregnancy and lactation, female rats were injected with 5 muCi of /sup 241/Am intravenously while nulliparous, pregnant or lactating. The females and subsequent litters were killed at various times after injection to determine /sup 241/Am distribution and retention. The temporal relationship between injection and pregnancy influenced the tissue retention of /sup 241/Am in both dams and progeny. The half-time of /sup 241/Am in livers of pregnant or lactating rats was more than twice that of nulliparous rats, although the initial uptake was approximately 50% of the activity in all groups. Both spleen and femur accumulated more /sup 241/Am at 7-10 weeks after injection than at earlier times, but this increase could not be related to pregnancy. Approximately 10 times more /sup 241/Am was transferred to offspring from dams that were lactating when exposed than was transferred via the placenta when exposure occurred late in gestation. Furthermore, more /sup 241/Am was transmitted to the progeny via milk if exposure of the dam occurred during lactation rather than during pregnancy.

Sasser, L.B.; Mahlum, D.D.; Rommereim, R.L.



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



Mesolimbic dopaminergic activity responding to acute stress is blunted in adolescent rats that experienced neonatal maternal separation.  


Neonatal maternal separation (MS), stressful experience early in life, leads to the development of depression-like behaviors in the offspring later in life. This study was conducted to define the neural basis of depression-like behaviors observed in our MS model. Sprague-Dawley pups were separated from dam for 3 h daily during the first 2 weeks of birth (MS) or left undisturbed (NH). All pups were sacrificed on postnatal day 41 with/without 1 h of restraint stress. Restraint stress significantly increased c-Fos expression in the nucleus accumbens (NAcb) of NH pups, but not in MS. In NH pups, restraint stress increased dopamine levels not only in the NAcb but also in the midbrain dopamine neurons; however, these increases were not observed in MS. Gene expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) was increased by acute restraint in NH pups, but not in MS pups. The raphe serotonin level was lower in MS than in NH, and not significantly changed by acute restraint neither in NH nor in MS. Results reveal that experience of neonatal MS may lead to a long-term suppression in the mesolimbic dopamine system of the offspring later in life, in which an epigenetic control may be implicated, such as suppressed gene expression of TH in the midbrain. We conclude that a decreased activity of the mesolimbic dopamine system may play a role in the pathophysiology of depression-like behaviors by neonatal MS, in addition to a decreased serotonin level in the raphe nucleus. PMID:20828601

Jahng, J W; Ryu, V; Yoo, S B; Noh, S J; Kim, J Y; Lee, J H



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


The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared with female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared with females and a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls. PMID:23426656

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



Separation stress, litter size, and the rewarding effects of low-dose morphine in the dams of maternally separated rats.  


Potential differences in sensitivity to the rewarding effects of morphine as a function of litter separation stress were assessed in post-weaning rat dams. During the first two weeks postnatal, Sprague-Dawley rat litters were subjected to daily 15- or 180-min sessions of dam-pup separation while control litters only experienced twice-weekly animal facility care. One week after weaning, the dams (n=7 per group) underwent a fully unbiased conditioned place preference (CPP) procedure to 1 mg/kg subcutaneous morphine. CPP responses after each conditioning cycle were recorded. Rates of acquisition and asymptotic levels of CPP were comparable in all groups; however, an inverse relationship between litter size and magnitude of morphine CPP was revealed. Although these initial data indicate no differential sensitivity to the rewarding effects of low-dose morphine produced by the stress of litter separation, this assessment of litter size and drug-induced place conditioning in post-weaning litter-separated dams is the first of its kind. Potential effects of other doses, drugs of abuse and post-partum manipulations remain to be evaluated within this emerging etiological model. PMID:17182163

Roma, Peter G; Huntsberry, Mary E; Riley, Anthony L



Perinatal maternal food restriction induces alterations in hypothalamo-pituitary-adrenal axis activity and in plasma corticosterone-binding globulin capacity of weaning rat pups.  


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) or both periods (PP group) in order to compare the long-term effects of gestational and/or lactational restriction. FR50 reduced the body growth of pups from the Post and PP groups as soon as day 11 until day 21 after birth. At weaning, pups of the Post and PP groups showed reduced adrenal, thymus and liver weights. Although the plasma adrenocorticotropic hormone (ACTH) level was reduced in pups, FR50 affected neither corticotropin-releasing hormone expression and peptide synthesis in the hypothalamus nor proopiomelanocortin expression in the adenohypophysis. Basal circulating levels of corticosterone were not markedly affected by FR50, but free corticosterone concentration was increased in the PP group. Plasma corticosterone-binding globulin (CBG) was decreased in newborns from both the Post and PP groups. Mineralocorticoid receptor gene expression was significantly increased in both CA1 and CA3 hippocampal areas in the PP group. Glucocorticoid receptor gene expression was increased in CA1, CA2 and dentate gyrus hippocampal areas in the Pre group, as well as in CA1, CA3 and DG areas in the Post group. The ether inhalation-induced plasma ACTH increase was weaker in pups from the Post and PP groups. Similarly, the ether inhalation-induced plasma corticosterone increase returned to basal levels in the Post group, or to weaker values than baseline in the PP group 90 min after this stressful procedure. The present work suggests that maternal food restriction during the perinatal period (gestation and lactation) or during lactation only reduces the postnatal somatic growth of pups and disturbs the activity of the HPA axis at weaning under both resting and stress conditions. A reduction in the plasma CBG-binding capacity, associated with a probable increase in hippocampal corticosteroid receptors, could reinforce glucocorticoid-mediated negative feedback and shorten stress-induced activation of the HPA axis in pups at weaning. PMID:11810034

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



Inflammation of the dam has different effects on the binding of maternal and fetal rat liver nucleoproteins to the rat haptoglobin gene promoter.  


Transcriptional regulation of binding interactions between nucleoproteins and the hormone response element (RE) of the rat haptoglobin (Hp) gene was investigated in adult and fetal livers of rats exposed to inflammation on day 19 of pregnancy. Nuclear extracts from the embryonal liver displayed a barely detectable binding-affinity for hormone RE, but in extracts from the adult liver it was noticeable. The acute phase reaction of the mother promoted an increase of Hp gene expression in both adult and fetal livers, relying on stage-specific changes in hormone RE binding activities of nucleoplasmic proteins. The results indicated that the elevation of Hp gene expression in fetal liver to the steady basal level found in adults required the induction of new trans-acting proteins, whereas an overexpression of this gene in adult acute phase liver relied essentially on an increase in the binding-affinity of the preexisting hormone RE binding proteins. PMID:7957771

Sevaljevi?, L; Petrovi?, M; Bogojevi?, D



Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats: influence of maternal Mg2+ supplementation.  


Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol- induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics itself. PMID:12213974

Wold, L E; Norby, F L; Hintz, K K; Colligan, P B; Epstein, P N; Ren, J



Exposure to maternal consumption of cafeteria diet during the lactation period programmes feeding behaviour in the rat.  


Lactational overfeeding programmes obesity in the adult rat, and also impacts on adult emotional behaviour. The present study investigated the impact of exposing the lactating female to a hypercaloric diet on structural aspects of feeding behaviour in the adult offspring as measured by the behavioural satiety sequence (BSS). Lactating Wistar rats were fed a hypercaloric cafeteria diet (CD) in addition to chow. Controls were fed on chow only. All offspring were chow fed after weaning. BSS was tested in 12-15 week old offspring. At 20 weeks of age, monoamine neurotransmitter levels were measured in selected brain regions. When exposed to a palatable 1-h test meal, offspring responded with the same latency to feed, regardless of lactational diet. Total food intake during the test was unaffected by lactational diet. Control offspring showed a normal BSS pattern. Male CD offspring displayed shorter feeding bouts (P<0.05) with an overall higher bout frequency (P<0.001) and their latency to rest was delayed (P<0.001). Overall eating frequency (P<0.05), but not duration was increased in male CD offspring. Although the transition from feeding to resting was not affected by lactational CD, CD males fed for longer at the beginning of the test meal and were more active towards the end. CD females displayed an increased number of feeding bouts (P<0.05) and they spent more time eating (P<0.05). Resting latency was delayed (P<0.05) and overall time spent resting was shortened (P<0.01). Frequency of eating was increased in the middle of the test meal. The onset of satiety as indicated by the transition point between eating and resting was delayed in CD females (P<0.001). In both sexes, hypothalamic 5-hydroxytryptamine (5-HT) was increased (P<0.05 in females, P<0.01 in males) and 5-HT turnover was reduced by lactational CD (P<0.001 in females, P<0.01 in males). Lactational CD led also to an increase in dopamine (DA) (P<0.01). Hypothalamic DA metabolism (DOPAC+HVA/DA ratio) was overall lower in females than in males (P<0.01). This study indicates a programming effect of lactational CD on feeding behaviour and brain monoaminergic neurons. PMID:22004940

Wright, Thomas M; Fone, Kevin C F; Langley-Evans, Simon C; Voigt, Jörg-Peter W




EPA Science Inventory

We hypothesize that maternal metallothionein (MT) induction by toxic dosages of chemicals may contribute to or cause developmental toxicity by the following chain of events: ) maternal hepatic MT induction; 2) redistribution of Zn to the newly synthesized MT; 3) decreased circula...


Insulin-like growth factors and binding proteins in the fetal rat: Alterations during maternal starvation and effects in fetal brain cell culture  

Microsoft Academic Search

Maternal malnutrition adversely affects fetal body and brain growth during late gestation. We utilized a fetal brain cell culture model to examine whether alternations in circulating factors may contribute to reduce brain growth during maternal starvation; we then used specific immunoassay and western blotting techniques, and purified peptides to investigate the potential role that altered levels of insulin-like growth factors

G. E. Shambaugh; J. A. Radosevich; R. P. Glick; D. S. Gu; B. E. Metzger; T. G. Unterman



Maternal food restriction during gestation elevates insulin-like growth factor I and insulin-like growth factor binding protein 1 in adult male rat offspring  

Microsoft Academic Search

Low birth weight due to maternal malnutrition is associated with increased risk of developing diseases in adulthood, for example, cardiovascular disease. Postnatal oxytocin treatment has previously been shown to have positive effects on blood pressure and corticosterone levels in adult offspring from malnourished dams. The aims of this study were to investigate if maternal food restriction during gestation alters plasma

Hanna Olausson; Moira Lewitt; Kerstin Brismar; Kerstin Uvnas-Moberg; Annica Sohlstrom



Maternal Gestational Dietary Fat has Minimal Effects on Serum Lipid Profiles and Hepatic Glucose Transporter 2 and No Effect on Glucokinase Expression in Neonatal Wistar Rat Offspring  

PubMed Central

The study investigated the effects of maternal diets, varying in fat content, on lipid profiles and the expression of hepatic glucose transporter 2 (GLUT2) and glucokinase (GK) in neonatal Wistar rat offspring. Dams were maintained on diets of 10% (control), 20% (20F), 30% (30F) and 40% (40F) fat as energy throughout gestation; daily food intakes and weekly body weights were measured. Circulating fasting glucose, insulin and glucagon concentrations were determined in dams and their neonatal offspring. In neonates, total serum triglyceride, total and individual serum fatty acid concentrations, hepatic GLUT2 and GK mRNA and protein expression were determined. In dams, overall food intake of 20F (645.50 ± 25.26 g) and 40F (716.30 ± 14.15 g) dams was reduced compared to control (1007.00 ± 44.83 g) and 30F (924.50 ± 21.16 g) dams. The 20F neonates displayed elevated blood glucose concentrations (4.63 ± 0.153 mmol/l) compared to control neonates (4.14 ± 0.112 mmol/l). In 30F neonates, serum palmitoleic acid was reduced (1.63 ± 0.21% vs. 3.56 ± 0.38%) whereas stearic acid was elevated (10.05 ± 0.40% vs. 7.40 ± 0.72%) compared to control neonates. Further, the palmitoleic acid/palmitic acid ratio was reduced in 30F neonates (0.085 ± 0.009% vs. 0.165 ± 0.020% in control neonates). The 40F neonates displayed elevated GLUT2 immunoreactivity (22.86 ± 0.760%) compared to 20F (11.46 ± 2.701%) and 30F (6.45 ± 1.759%) neonates. Gestational programming with different dietary fat proportions minimally affects lipid profiles and hepatic GLUT2 immunoreactivity in neonatal offspring.

Cerf, Marlon E.; Williams, Keith; Muller, Christo J.; Louw, Johan



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

PubMed Central

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

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



Sex-dependent effects of early maternal deprivation on MDMA-induced conditioned place preference in adolescent rats: possible neurochemical correlates.  


The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of abuse. In the present study we have used the conditioned place preference (CPP) paradigm to address the influence of MD on the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in adolescent animals of both sexes. We have previously observed in adolescent rats that MD induces modifications in the serotonergic and endocannabinoid systems, which play a role in the rewarding effects of MDMA. In light of this evidence, we hypothesized that MD would alter the psychobiological consequences of exposure to MDMA. Neonatal Wistar rats underwent MD (24h, on PND 9) or were left undisturbed (controls). The animals were conditioned with 2.5mg/kg MDMA during the periadolescent period (PND 34-PND 43) and were tested in the open-field test at the end of adolescence (PND 60). Animals were sacrificed on PND 68-75 and levels of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid were measured in the striatum, hippocampus and cortex, while the expression of hippocampal CB1 cannabinoid receptor (CB1R) and circulating levels of corticosterone and leptin were also measured. Control males showed CPP after administration of MDMA. However, no MDMA-induced CPP was detected in control females or MD males, and MD had no effect on open field activity in any group. A reduction in striatal and cortical 5-HT levels, increased expression of hippocampal CB1R and a marked trend towards higher circulating leptin levels were observed in MDMA-treated MD males. Our results demonstrate for the first time that MD reduces the rewarding effects of MDMA in a sex-dependent manner. We propose that this effect is related, at least in part, with alterations of the serotonergic and cannabinoid systems. PMID:23246480

Llorente-Berzal, Alvaro; Manzanedo, Carmen; Daza-Losada, Manuel; Valero, Manuel; López-Gallardo, Meritxell; Aguilar, María A; Rodríguez-Arias, Marta; Miñarro, José; Viveros, Maria-Paz



Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function.  


We have previously reported that offspring of mothers fed a high fat (HF) diet during pregnancy and lactation enter puberty early and are hyperleptinaemic, hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also impact offspring development and disease risk.We therefore hypothesized that prenatal nutrition would affect maternal care and that an interaction may exist between a maternal HF diet and maternal care, subsequently impacting on offspring phenotype.Wistar rats were mated and randomized to control dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Maternal care was assessed by observing maternal licking and grooming of pups between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a control (–con) or HF (–hf) diet. From P27, pubertal onset was assessed. At ?P105 oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF-fed mothers licked and groomed pups less than CON dams.Maternal fat:lean ratio was higher in HF dams at weaning and was associated with higher maternal plasma leptin and insulin concentrations, but there was no effect of maternal care on fat:lean ratio or maternal hormone levels. Both female and male offspring of HF dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF offspring were heavier than controls. Prepubertal retroperitoneal fat mass was greater in pups from HF-fed dams compared to CON and was associated with elevated circulating leptin concentrations in females only, but there was neither an effect of maternal care, nor an interaction between maternal diet and care on prepubertal fat mass. Pups from HF-fed dams went into puberty early and this effect was exacerbated by a postweaning HF diet.Maternal and postweaning HF diets independently altered oestrous cyclicity in females: female offspring of HF-fed mothers were more likely to have prolonged or persistent oestrus, whilst female offspring fed a HF diet postweaning were more likely to have irregular oestrous cycles and were more likely to have prolonged or persistent oestrus. These data indicate that maternal HF nutrition during pregnancy and lactation results in a maternal obese phenotype and has significant impact on maternal care during lactation. Maternal and postweaning nutritional signals, independent of maternal care, alter offspring body fat pre-puberty and female reproductive function in adulthood, which may be associated with advanced ovarian ageing and altered fertility. PMID:22411006

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



Comparison of DNA alkylation, fragmentation, and repair in maternal and fetal tissues of pregnant rats treated with a single dose of ethyl methanesulfonate, ethyl-N-nitrosourea, N-nitrosodiethylamine, and methyl-N-nitrosourea.  


The occurrence and persistence of DNA damage, as detected by the alkaline elution technique, have been studied in some tissues of both fetal and adult Sprague-Dawley rats (18th day of gestation) after administration of a single equimolar dose (0.5 mmol/kg) of ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), N-nitrosodiethylamine (NDEA), and N-methyl-N-nitrosourea (MNU). EMS, ENU, and MNU, injected intravenously, produced a statistically significant increase of DNA elution rate, which is considered indicative of DNA fragmentation, in both maternal and fetal liver, kidney, and brain. NDEA, introduced by gastric gavage, induced DNA breaks in both liver and kidney of dams, but only in the liver of fetuses. The frequency of DNA lesions was found to vary with the four alkylating agents and in the three organs tested, to exhibit a different time course, and usually to be higher in maternal than in fetal tissues. Results provided by the concomitant determination of DNA binding levels demonstrated a satisfactory correlation with the amounts of DNA fragmentation. In contrast, the values of both these parameters did not show any positive correlation with the different susceptibility of the three organs to tumor induction. In conclusion, these findings suggest that when a compound is not available in radiolabeled form, measurement of DNA fragmentation may represent a useful alternative to the determination of DNA binding level in order to obtain information on the distribution of its reactive species in maternal and fetal tissues. PMID:2570470

Robbiano, L; Parodi, A; Venturelli, S; Brambilla, G



Role of Metallothionein Induction and Altered Zinc Status in Maternally Mediated Developmental Toxicity: Comparison of the Effects of Urethane and Styrene in Rats.  

National Technical Information Service (NTIS)

The authors hypothesize that maternal metallothionein (MT) induction by toxic dosages of chemicals may contribute to or cause developmental toxicity by a chain of events leading to a transient but developmentally adverse decrease in Zn availability to the...

G. P. Daston G. J. Overmann M. W. Taubeneck L. D. Lehman-McKeeman J. M. Rogers



Sister-Chromatid Exchange Induction in Rat Maternal, Embryonic and Extra-Embryonic Cells After in vivo Exposure to 4-Nitroquinoline 1-Oxide.  

National Technical Information Service (NTIS)

Genetic damage is associated with various embryo pathologies; and many teratogens and transplacental carcinogens are known to be genotoxic. The present study was aimed at charaterizing SCE induction levels in rodent maternal, embryonic and extra-embryonic...

R. K. Sharma R. Dunn J. W. Allen



Folic Acid and Protein Content in Maternal Diet and Postnatal High-Fat Feeding Affect the Tissue Levels of Iron, Zinc, and Copper in the Rat  

Microsoft Academic Search

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies\\u000a present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present\\u000a study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys\\u000a of adult

Ewelina Król; Zbigniew Krejpcio; Agata Chmurzynska


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



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



Development of maternal identity  

Microsoft Academic Search

Reva Rubin suggested in her theoretical framework that developmental tasks were necessary for a woman to achieve maternal identity post partum. Rubin defined maternal identity as the woman's internal sense of competence in the maternal role and her knowledge of her infant. If measures of pregnancy developmental tasks could predict maternal identity such measures would be helpful in determining women

Sharon Lynn Dore



Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting.  


Evidence suggests that insulin-like growth factors-I and -II (IGF-I and II) play a role in regulating fetal growth and development. In the fetus, IGF-I and -II are complexed with two specific binding proteins (IGFBP-1 and -2), which are thought to modulate the actions of the IGFs in target tissues. We examined regulation of the genes for IGF-I, IGF-II, IGFBP-1, and IGFBP-2 in fetal rat liver in an experimental model for intrauterine growth retardation caused by maternal fasting on days 17-21 of gestation. The mean weight of fetuses from the fasted dams was 27-32% lower than the mean weight of fetuses from the fed dams. The concentration of immunoreactive IGF-I was decreased by 71% in serum of fetuses from the fasting dams. The concentration of immunoreactive IGF-II was slightly decreased (by 12%) in serum of fetuses from the fasting dams, whereas the concentration of immunoreactive pro-IGF-II E-domain peptide was decreased by 31%. The abundance of hepatic IGF-I mRNA was decreased by 55% in fetuses from the fasting dams. In contrast, the abundance of IGF-II mRNA in fetal liver was not significantly decreased by maternal fasting. Maternal fasting caused a 2-fold increase in the abundance of IGFBP-1 mRNA in fetal liver, whereas it did not change the abundance of IGFBP-2 mRNA. The induction of IGFBP-1 mRNA in liver of the growth-retarded fetuses is similar to the induction that occurs in liver of fasting adults, while the lack of regulation of IGFBP-2 mRNA differs from the strong induction of IGFBP-2 mRNA that occurs in liver of fasting adults. In summary, these results indicate that maternal fasting causes a decrease in fetal IGF-I gene expression, a decrease in fetal serum IGF-I, and a slight decrease in fetal serum IGF-II and pro-IGF-II E-domain peptide concentrations. Maternal fasting also causes an increase in fetal IGFBP-1 gene expression. Changes in fetal insulin and glucose may be related to changes in expression of the IGF-I and IGFBP-1 genes in the growth-retarded fetuses. The decreased expression of IGF-I and -II and increased expression of the IGFBP-1 gene may contribute to the fetal growth retardation observed in this model system. PMID:1846108

Straus, D S; Ooi, G T; Orlowski, C C; Rechler, M M



Down-regulation of GAT1 mRNA expression in the microdissected hypothalamic medial preoptic area of rat offspring exposed maternally to ethinylestradiol  

Microsoft Academic Search

Steroid hormones are powerful regulators of gene transcription in the brain and have the potential to permanently alter the structure and function of the developing brain. Steroid-mediated altered gene expression may thus be responsible for the molecular cascade for sexual differentiation. In this study, to assess effects of maternal exposure to ethinylestradiol (EE) on brain sexual differentiation of offspring, region-specific

Makoto Shibutani; Naoya Masutomi; Chikako Uneyama; Naoko Abe; Hironori Takagi; Kyoung-Youl Lee; Masao Hirose



Maternal deprivation and early handling affect density of calcium binding protein-containing neurons in selected brain regions and emotional behavior in periadolescent rats  

Microsoft Academic Search

Adverse early life experiences can induce neurochemical changes that may underlie modifications in hypothalamic–pituitary–adrenal axis responsiveness, emotionality and cognition. Here, we investigated the expression of the calcium binding proteins (CBPs) calretinin, calbindin and parvalbumin, which identify subpopulations of GABAergic neurons and serve important functional roles by buffering intracellular calcium levels, following brief (early handling) and long (maternal deprivation) periods of

C. Giachino; N. Canalia; F. Capone; A. Fasolo; E. Alleva; M. A. Riva; F. Cirulli; P. Peretto



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...


Natural variations in postpartum maternal care in inbred and outbred mice  

Microsoft Academic Search

The role of maternal care in mediating variation in offspring phenotype has been examined in the rat and demonstrates that mother–infant interactions are critical for inducing long-term changes in behavior. Though phenotypic differences between mice strains are often attributed to genetic factors, the influence of early maternal environment has not been extensively explored. To understand maternal influence on phenotype in

Frances A. Champagne; James P. Curley; Eric B. Keverne; Patrick P. G. Bateson



Does maternal dietary mineral restriction per se predispose the offspring to insulin resistance?  

Microsoft Academic Search

Background: Maternal undernutrition is hypothesized to predispose the offspring to disease in adult life. The relevance of maternal macronutrient deficiency has been well studied but not that of micronutrients. Objective: To assess the effect of maternal dietary mineral restriction per se on oral glucose tolerance (OGT), insulin resistance (IR) and fat metabolism in offspring. Design: Female weanling Wistar\\/NIN rats received

Lagishetty Venu; Nemani Harishankar; Tripuraribhatla Prasanna Krishna; Manchala Raghunath



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



Foetal mortality in moderately zinc-deficient rats is strictly related to the process of parturition: effect of maternal essential fatty acid supplementation.  


1. Although disrupted parturition and high foetal losses have previously been reported in pregnant rats maintained on zinc-deficient diets this is the first report to differentiate between the effects of reduced Zn intake and the effects of reduced food intake on the outcome of pregnancy in the rat. 2. Rats maintained on a 0.5 mg Zn/kg diet for the last 7 d of gestation or on a 5 mg Zn/kg diet throughout gestation did not consume significantly less food than rats given 10 or 20 mg Zn/kg diets except during the last 2d of gestation. Pair-feeding of Zn-adequate rats (20 mg/kg) to those given low-Zn diets for the last 2 d of gestation did not affect the outcome of pregnancy in these rats. 3. In the rats maintained throughout gestation on 5 mg Zn/kg or on 0.5 mg Zn/kg in the last 7 d of gestation, parturition onset and duration were not significantly altered. Foetal survival was very significantly reduced but only from day 22 onwards; before the onset of parturition, foetal survival was not significantly affected by Zn deficiency during gestation. 4. Subcutaneous injection of evening primrose (Oenothera biennis) oil into rats throughout gestation enhanced foetal and neonatal survival in rats given 5 mg Zn/kg but reduced foetal survival in rats given 0.5 mg Zn/kg in the last 7 d of gestation. 5. The results suggest three points: (1) subtotal Zn deficiency during gestation in the rat jeopardises foetal survival at parturition without affecting the onset or duration of parturition, (2) foetal death in rats maintained on Zn-deficient diets occurs only in relation to parturition itself, (3) provided that Zn intake near term is at least 5 mg/kg, supplemental essential fatty acids (evening primrose oil) will reduce foetal mortality during parturition and in the neonatal period. PMID:7082621

Cunnane, S C



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



Role of the Midbrain Periaqueductal Gray in Maternal Nurturance and Aggression: c-fos and Electrolytic Lesion Studies in Lactating Rats  

Microsoft Academic Search

The upright crouched, or kyphotic, nursing posture of lactating rats is dependent on suckling stimulation from pups. Because of the neuroanatomical connections of the periaqueductal gray (PAG) and its sensorimotor integration of the analogous lordo- sis posture displayed by sexually receptive female rats, the possible role of the PAG in kyphosis was investigated using c-fos immunocytochemistry and electrolytic lesions. Lactating

Joseph S. Lonstein; Judith M. Stern



Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood  

Microsoft Academic Search

Objective: This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. Methods: For two experiments, pregnant rats were injected with LPS (250 ?g\\/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6)

Maria M. Bernardi; Thiago B. Kirsten; Suzana M. Matsuoka; Elizabeth Teodorov; Soraya F. Habr; Sandra H. W. N. Penteado; João Palermo-Neto



Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system.  


Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system. PMID:18666205

Llorente, Ricardo; Llorente-Berzal, Alvaro; Petrosino, Stefania; Marco, Eva-María; Guaza, Carmen; Prada, Carmen; López-Gallardo, Meritxell; Di Marzo, Vincenzo; Viveros, María-Paz



Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription.  


Caffeine is a widely used psychostimulant freely crossing the placental barrier. At the doses usually absorbed, it acts as an antagonist of both A1 and A2A adenosine receptors. Pregnant women are generally not advised to limit their caffeine consumption and thus expose their progeny to the drug during the whole of gestation and lactation. The possibility that such caffeine exposure may have long-term consequences on brain development has led to several behavioral investigations on animal models. Despite the crucial role played by adenosine receptor systems in neonatal breathing control, few studies in vitro have been concerned with the consequences of maternal caffeine absorption on breathing, and none in the unrestrained intact animal. The present investigation analyzed the influence of caffeine exposure via placental and milk transfer on resting ventilation and on the response to moderate alveolar hypoxia of 0 to 2-day-old newborn rat (P0-P2) together with the possible underlying mechanisms. Dams absorbed caffeine (46+/-3 mg/kg/day) via drinking fluid (0.2 g/L) throughout gestation, in conditions mimicking moderate human consumption. Caffeine exposure did not significantly affect basal respiratory parameters. In contrast, it attenuated both the early increase and the secondary decrease in ventilation triggered by moderate alveolar hypoxia (11% O2 inhaled). The abolition of Fos protein expression evoked by hypoxia suggested that caffeine exposure may decrease the activity of O2-sensing peripheral chemoreceptor pathway. From real-time PCR data, those functional alterations were associated to increases in A2A adenosine receptor and alpha2 GABA(A) receptor subunit mRNAs in the medulla. This indicates that, even at moderate doses, maternal caffeine consumption may induce a series of subtle developmental alterations that may affect modulation of breathing control in the neonate in pathological situations such hypoxia. PMID:18706486

Picard, N; Guénin, S; Larnicol, N; Perrin, Y



Quantitative estimation of dietary energy deficiency and effects of its supplementation on protein nutritional status of nondiabetic uremic patients undergoing protein restricted dietary regimens.  


In chronic renal failure (CRF) patients with a reduced protein intake, if the patients' energy intake could be estimated on the basis of biochemical data together with protein intake, it would be easier to provide them with adequate dietary treatment. Thus, from the relationship among the normalized protein catabolic rate (nPCR) and the intrinsic creatinine generation rate (%GCr) both calculated on the basis of 24-hr urine creatinine, as well as the daily dietary energy intake evaluated by a skilled nutritionist, we devised the following equation to estimate the amount of dietary energy deficiency (delta E) whose supplementation increases the %GCr of patients on protein-restricted dietary regimens to the target level (i.e., the dietary energy deficient amount). This was done by taking the %GCr of average nondiabetic hemodialysis patients of the same age and sex as a temporal target level: delta E = [31.22 - 1.97 (%GCr)0.6]/(nPCR)0.15. In order to examine the clinical usefulness of this equation, the daily dietary energy deficient amount calculated by the equation was supplemented with protein-free jelly. As a result, the %GCr increased from approximately three-fourths of the target level to the target level within 4 months. PMID:11486599

Iwayama, N; Shinzato, T; Nakai, S; Ando, S; Nagake, Y; Makino, H; Maeda, K




Microsoft Academic Search

When female rats are fed a protein-deficient diet (6% protein by weight) for 2 weeks prior to and during gestation, the offspring exhibit deficits in body weight, epididymal fat pad weight and the size and number of adipocytes which cannot be corrected by an adequate post-natal diet. However, the plasma cholesterol, triglyceride and glucose concentrations are similar in the progeny

Katrine I McLeod; PJ Nestel; RB Goldrick



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


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

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



The neurobiology of infant maternal odor learning  

PubMed Central

Infant rats must learn to identify their mother’s diet-dependent odor. Once learned, maternal odor controls pups’ approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Raineki, C.; Pickenhagen, A.; Roth, T.L.; Babstock, D.M.; McLean, J.H.; Harley, C.W.; Lucion, A.B.; Sullivan, R.M.



Effects of maternal ingestion of aroclor 1254 (PCB) on the development pattern of oxygen consumption and body temperature in neonatal rats  

SciTech Connect

Polychlorinated biphenyl (PCB) is an environmental pollutant that has been implicated in depression of reproductive success in Great Lakes gulls, production of congenital deformities in humans, and increased incidence of carcinogenesis in laboratory mice. PCB has also been shown to be a thyrotoxin in both adult and developing animals. Most recently, the hypothyroid effects of PCB exposure have been reported to elicit effects similar to those of hypothyroidism caused by other methods. This study was done to determine the effects of PCB ingestion in pregnant and lactating rats on the development of thermoregulation in neonatal animals. Body temperature and rate of oxygen consumption was evaluated in rat puts on days 4 through 14 after birth. Because the major thermomregulatory hormones are thyroid hormones, thyroid hormone status and thyroid weights were evaluated at the end of the study on postnatal day 15. 19 refs., 2 figs., 1 tab.

Seo, B.W.; Meserve, L.A. [Bowling Green State Univ., OH (United States)



Maternal behavior in cattle  

Microsoft Academic Search

We provide a critical summary of the literature on maternal behavior in cattle. The studies we review increase our basic understanding of this behavior and provide insights into practical problems in cattle production. When domesticated cattle are permitted to rear their young, the behaviors associated with maternal care are for the most part similar to those observed in wild ungulates.

Marina A. G. von Keyserlingk; Daniel M. Weary



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

Microsoft Academic Search

The goal of the present study is to assess the effects of anticancer treatment with cyclophosphamide and cytarabine during pregnancy on the mineralization of mandible bones in 7-, 14- and 28-day-old rats. Each bone sample was described by its X-ray fluorescence spectrum characterizing the mineral composition. The data collected are multivariate in nature and their structure is difficult to visualize

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



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

Microsoft Academic Search

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

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



Fetal Dexamethasone Exposure Affects Basal Ornithine Decarboxylase Activity in Developing Rat Brain Regions and Alters Acute Responses to Hypoxia and Maternal Separation  

Microsoft Academic Search

Although glucocorticoids are widely used to stimulate fetal\\/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg\\/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions.

R. Q. Carlos; F. J. Seidler; S. E. Lappi; T. A. Slotkin



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


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

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



Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration  

Microsoft Academic Search

Rationale  Early environment can shape the development and function of the mesocorticolimbic dopamine (DA) system and represents a possible\\u000a risk factor for adult pathologies. One critical variable in the early environment is nutrition, and exposure to high fat (HF)\\u000a in adulthood is known to change this DA system.\\u000a \\u000a \\u000a \\u000a Objectives  We tested whether perinatal HF intake in rats could have long-term effects on

Lindsay Naef; Lalit Srivastava; Alain Gratton; Howard Hendrickson; S. Michael Owens; Claire-Dominique Walker



The maternal autopsy  

PubMed Central

Careful study of reports prepared for the Confidential Enquiries into Maternal Deaths in England and Wales has made it clear that many maternal autopsy reports are not as informative as they might be. This is, in part at least, because no pathologist who does not work in a maternity unit can expect to see more than a handful of such deaths in a working lifetime. This paper describes briefly the particular features to look for at autopsy, stresses the importance of taking adequate material for histology and discusses some of the more significant histological findings, both of conditions which cause death and of those commonly associated with it. Images

Rushton, DI; Dawson, IMP



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

Microsoft Academic Search

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

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



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


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

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



Maternal inexperience as a risk factor of innate fear and PTSD-like symptoms in mice  

Microsoft Academic Search

In laboratory rats and mice, differences in maternal care during the first week of life have been shown to exert long-lasting consequences on cognitive functioning and stress processing of the offspring. Such epigenetic programming is also assumed to play an important role in the transgenerational transmission of PTSD in humans. Here we studied whether even subtle within-subject differences in maternal

Anja Siegmund; Maik Dahlhoff; Ursula Habersetzer; Anna Mederer; Eckhard Wolf; Florian Holsboer; Carsten T. Wotjak



Global uterine and blastocyst gene expression patterns associated with maternal overweight at conception  

Technology Transfer Automated Retrieval System (TEKTRAN)

Exposure to maternal overweight (OW) increases the risk of obesity in adult-life. Maternal OW was induced in rats by overfeeding via total enteral nutrition. Male offspring from OW dams gain greater body weight, fat mass and develop insulin resistance when fed high fat diets (45% fat). This is assoc...


Maternal obesity during conception programs offspring's body composition: Modulation of fatty acid synthase expression  

Technology Transfer Automated Retrieval System (TEKTRAN)

The risk of obesity in later 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 by intragastric feeding of diets using total...


Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring  

Microsoft Academic Search

Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study

Richard O. C Oreffo; Benjamin Lashbrooke; Helmtrud I Roach; Nicholas M. P Clarke; Cyrus Cooper



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

National Technical Information Service (NTIS)

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

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