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Sample records for adult offspring rats

  1. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring.

  2. Prenatal nicotine exposure results in the myocardial fibrosis in the adult male offspring rats.

    PubMed

    Yu, Feng; Zheng, Aiqiang; Qian, Jin; Li, Yuexia; Wu, Lei; Yang, Jian; Gao, Xiren

    2016-09-01

    Our previous study showed that prenatal nicotine exposure could increase the heart rate of adult male offspring rats, but little is known about the mechanism. The aim of this study was to investigate the mechanism. Nicotine was subcutaneously administered to pregnant rats at a dose of 1.5mgkg(-1) from the gestational days 3-21; the control group received the same volume of saline by the same route. The offsprings' heart weight, ejection function, ultrastructure, and blood hormones were determined. The present study exhibited that prenatal nicotine exposure significantly decreased the offsprings' heart and body weight at gestational day 21 and at day 15 after birth, but had no effect on the heart and body weight at 90 days after birth. The hearts were fibrosed in the nicotine exposed male offsprings, and the heart ejection functions of the nicotine male offsprings at 90 days after birth were decreased, including SV, FS and EF. In addition, prenatal nicotine exposure significantly increased the offspring's blood adrenaline and norepinephrine levels. These data suggest that the increased heart rate caused by prenatal nicotine exposure may be a result of myocardial fibrosis, which leads to heart function decreases, and these data imply a myocardial fibrosis risk of prenatal nicotine exposure.

  3. Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

    PubMed

    Pittet, Florent; Babb, Jessica A; Carini, Lindsay; Nephew, Benjamin C

    2017-04-01

    We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

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

    SciTech Connect

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

    2011-03-01

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

  5. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    PubMed

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  6. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)--a phytoalexin known to confer cardiovascular protection--could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg; P=0.007), and nitric oxide synthase inhibition (with L-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment with L-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%; P<0.05), and this difference could be normalized by L-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats.

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

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

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

  8. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life.

  9. Estrogen normalizes perinatal nicotine-induced hypertensive responses in adult female rat offspring.

    PubMed

    Xiao, Daliao; Huang, Xiaohui; Yang, Shumei; Zhang, Lubo

    2013-06-01

    Perinatal nicotine exposure caused a sex-dependent heightened vascular response to angiotensin II (Ang II) and increased blood pressure in adult male but not in female rat offspring. The present study tested the hypothesis that estrogen normalizes perinatal nicotine-induced hypertensive response to Ang II in female offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. Ovariectomy and 17β-estradiol replacement were performed on 8-week-old female offspring. At 5 months of age, Ang II-induced blood pressure responses were not changed by nicotine treatment in the sham groups. In contrast, nicotine significantly enhanced Ang II-induced blood pressure responses as compared with saline control in the ovariectomy groups, which was associated with increased Ang II-induced vascular contractions. These heightened responses were abrogated by 17β-estradiol replacement. In addition, nicotine enhanced Ang II receptor type I, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase type 2 protein expressions, and reactive oxygen species production of aortas as compared with saline control in the ovariectomy groups. Antioxidative agents, both apocynin and tempol, inhibited Ang II-induced vascular contraction and eliminated the differences of contractions between nicotine-treated and control ovariectomy rats. These findings support a key role of estrogen in the sex difference of perinatal nicotine-induced programming of vascular dysfunction, and suggest that estrogen may counteract heightened reactive oxygen species production, leading to protection of females from development programming of hypertensive phenotype in adulthood.

  10. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  11. The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats.

    PubMed

    Karbalaei, Narges; Ghasemi, Asghar; Hedayati, Mehdi; Godini, Aliashraf; Zahediasl, Saleh

    2014-04-01

    Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of β-cells.

  12. Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

    PubMed

    Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

    2015-01-01

    Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.

  13. Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring.

    PubMed

    Karbaschi, Roxana; Sadeghimahalli, Forouzan; Zardooz, Homeira

    2016-09-01

    This study attempts to further clarify the potential effects of maternal high-fat (HF) diet on glucose homeostasis in dams and young adult male rat offspring. Female rats were divided into control (CON dams) and HF (HF dams) diet groups, which received the diet 4 weeks prior to and through pregnancy and lactation periods. Blood samples were taken to determine metabolic parameters, then an intraperitoneal glucose tolerance test (IPGTT) was performed. Maternal HF diet increased intra-abdominal fat mass and plasma corticosterone level, but decreased leptin concentration in dams. In HF offspring intra-abdominal fat mass, plasma leptin, and corticosterone levels decreased. Following IPGTT, the plasma insulin level of HF dams was higher than the controls. In HF offspring plasma insulin level was not significantly different from the controls, but a steeper decrease of their plasma glucose concentration was observed.

  14. Maternal arachidonic acid supplementation improves neurodevelopment in young adult offspring from rat dams with and without diabetes.

    PubMed

    Zhao, Jinping; Del Bigio, Marc R; Weiler, Hope A

    2011-01-01

    Maternal diabetes may compromise infant arachidonic acid (AA) status and development. This study tested if maternal AA supplementation improves neurodevelopment in adult offspring. Rat dams were randomized into 6 groups: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed either a Control or AA (0.5% fat) diet throughout reproduction. Weaned-offspring were fed regular chow to 12 weeks of age. Testing included exploratory behavior, rota rod and water maze (WM). Poorly controlled offspring showed longer (p≤0.018) escape-latency on testing-day 1 WM but not thereafter (p>0.05). Maternal glucose concentration positively correlated with (p=0.006) male offspring testing-day 1 WM latency. The AA-diet offspring performed better in WM and rota rod (p≤0.032) and showed higher exploratory behavior (p=0.008) than Control-diet offspring. These data suggest maternal hyperglycemia has longstanding consequences to initial stages of learning in the offspring. Maternal AA supplementation and training positively influence learning outcomes.

  15. Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

    PubMed Central

    Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

    2016-01-01

    A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

  16. Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

    PubMed

    Casimiro-Lopes, G; Lisboa, P C; Koury, J C; Boaventura, G; Passos, M C F; Moura, E G

    2012-02-01

    Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.

  17. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  18. Prenatal Inflammation-Induced Hypoferremia Alters Dopamine Function in the Adult Offspring in Rat: Relevance for Schizophrenia

    PubMed Central

    Aguilar-Valles, Argel; Flores, Cecilia; Luheshi, Giamal N.

    2010-01-01

    Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring's dopamine function. Using a rat model of localized injury induced by turpentine, which triggers the innate immune response and inflammation, we investigated the effects of maternal iron supplementation on the offspring's dopamine function by assessing behavioral responses to acute and repeated administration of the dopamine indirect agonist, amphetamine. In addition we measured protein levels of tyrosine hydroxylase, and tissue levels of dopamine and its metabolites, in ventral tegmental area, susbtantia nigra, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Offspring of turpentine-treated mothers exhibited greater responses to a single amphetamine injection and enhanced behavioral sensitization following repeated exposure to this drug, when compared to control offspring. These behavioral changes were accompanied by increased baseline levels of tyrosine hydroxylase, dopamine and its metabolites, selectively in the nucleus accumbens. Both, the behavioral and neurochemical changes were prevented by maternal iron supplementation. Localized prenatal inflammation induced a deregulation in iron homeostasis, which resulted in fundamental alterations in dopamine function and behavioral alterations in the adult offspring. These changes are characteristic of schizophrenia symptoms in humans. PMID:20532043

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  20. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    SciTech Connect

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-05-28

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  1. Targeting arachidonic acid pathway to prevent programmed hypertension in maternal fructose-fed male adult rat offspring.

    PubMed

    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

    2016-12-01

    Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ2. In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ2 treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE2 levels in adult offspring kidney exposed to maternal HF. 15dPGJ2 therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake.

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

    PubMed Central

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

    2016-01-01

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

  3. Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring.

    PubMed

    Porter, James P; King, Summer H; Honeycutt, April D

    2007-07-01

    Several animal models have been developed to study fetal programming of hypertension. One model involves feeding high-salt (HS) diet to rats before and during pregnancy, during lactation, and after weaning for 10 days. In the present investigation, we limited HS diet to the prenatal period in an attempt to find a narrower critical window for fetal programming. The HS diet did not result in low-birth weight offspring. In the adult offspring, radiotelemetry was used to assess blood pressure and heart rate in the conscious unstressed state. As adults, the HS offspring were not hypertensive compared with normal-salt (NS) control animals. However, the pressor and tachycardic responses to 1-h of restraint were significantly enhanced in HS female offspring, and recovery after restraint was delayed. This was accompanied by an increase in relative expression of corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus during basal and stressed conditions. There was no augmented stress response or relative increase in CRH mRNA in adult HS male offspring. When challenged with 1 wk of 8% NaCl diet as adults, neither HS male nor female offspring exhibited salt sensitivity compared with NS groups. These data show that a high-salt diet limited to the prenatal period is not sufficient to program hypertension in adult offspring. However, this narrower critical period is sufficient to imprint a lasting hyperresponsiveness to stress, at least in adult female offspring. These data indicate that excessive maternal salt intake during pregnancy can adversely affect the cardiovascular health of adult offspring.

  4. Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring.

    PubMed

    Lacy, Ryan T; Brown, Russell W; Morgan, Amanda J; Mactutus, Charles F; Harrod, Steven B

    2016-01-01

    In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth weight in offspring, but it can also negatively influence neurodevelopmental outcomes in later stages of life, such as an increased incidence of obesity and drug abuse. Animal models demonstrate that prenatal nicotine (PN) alters the development of the mesocorticolimbic system, which is important for organizing goal-directed behavior. In the present study, we determined whether intravenous (IV) PN altered the initiation and/or expression of methamphetamine (METH)-induced locomotor sensitization as a measure of mesocorticolimbic function in adult rat offspring. We also determined whether PN and/or METH exposure altered protein levels of BDNF (brain-derived neurotrophic factor) in the nucleus accumbens, the dorsal striatum, and the prefrontal cortex of adult offspring. BDNF was of interest because of its role in the development and maintenance of the mesocorticolimbic pathway and its ability to modulate neural processes that contribute to drug abuse, such as sensitization of the dopamine system. Dams were injected with IV nicotine (0.05 mg/kg/injection) or saline, 3×/day on gestational days 8-21. Testing was conducted when offspring reached adulthood (around postnatal day 90). Following 3 once daily habituation sessions the animals received a saline injection and baseline locomotor activity was measured. PN and prenatal saline (PS)-exposed offspring then received 10 once daily injections of METH (0.3 mg/kg) to induce locomotor sensitization. The animals received a METH injection (0.3 mg/kg) to assess the expression of sensitization following a 14-day period of no injections. A day later, all animals were injected with saline and conditioned hyperactivity was assessed. Brain tissue was harvested 24 h later. PN animals habituated more slowly to the activity chambers

  5. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats

    PubMed Central

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure. PMID:27760213

  6. Altered Health Outcomes in Adult Offspring of Sprague Dawley and Wistar Rats Undernourished During Early or Late Pregnancy

    EPA Science Inventory

    Gestational undernutrition in humans can result in birth weight reductions (an indicator of a suboptimal intrauterine environment) and predisposition to adult disease in offspring including high blood pressure, insulin resistance, glucose intolerance, and obesity (key components ...

  7. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    EPA Science Inventory

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  8. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  9. Ingestion of Carbohydrate-Rich Supplements during Gestation Programs Insulin and Leptin Resistance but not Body Weight Gain in Adult Rat Offspring.

    PubMed

    Beck, Bernard; Richy, Sébastien; Archer, Zoe A; Mercer, Julian G

    2012-01-01

    Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important modifications in hormonal status is a period of changes in normal feeding habits with pulses of consumption or avoidance of certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their daily intake with either a restricted control (Cr), high-fat (HF), or high-carbohydrate (HC) diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca) served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin) were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females (-16%; p < 0.001) and their offspring presented a weight deficit from birth until 6 (HC group) and 10 (Cr group) weeks of age (p < 0.05 or less). Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose, and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%; p < 0.001), but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC, and HF offspring (+33-100% vs Ca; p < 0.05 or less). HC supplement ingestion during gestation therefore leads to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest that attention should be paid to the carbohydrate snacking and overall carbohydrate content in the diet during the last weeks (or months) preceding delivery to limit development of later metabolic disorders in offspring.

  10. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

    PubMed Central

    Chowdhury, Sabiha S.; Lecomte, Virginie; Erlich, Jonathan H.; Maloney, Christopher A.; Morris, Margaret J.

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  11. Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

    PubMed Central

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J.; Poston, Lucilla; Taylor, Paul D.

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  12. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.

  13. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring1

    PubMed Central

    Tsoulis, Michael W.; Chang, Pauline E.; Moore, Caroline J.; Chan, Kaitlyn A.; Gohir, Wajiha; Petrik, James J.; Vickers, Mark H.; Connor, Kristin L.; Sloboda, Deborah M.

    2016-01-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  14. Alteration of mitochondrial function in adult rat offspring of malnourished dams

    PubMed Central

    Reusens, Brigitte; Theys, Nicolas; Remacle, Claude

    2011-01-01

    Under-nutrition as well as over-nutrition during pregnancy has been associated with the development of adult diseases such as diabetes and obesity. Both epigenetic modifications and programming of the mitochondrial function have been recently proposed to explain how altered intrauterine metabolic environment may produce such a phenotype. This review aims to report data reported in several animal models of fetal malnutrition due to maternal low protein or low calorie diet, high fat diet as well as reduction in placental blood flow. We focus our overview on the β cell. We highlight that, notwithstanding early nutritional events, mitochondrial dysfunctions resulting from different alteration by diet or gender are programmed. This may explain the higher propensity to develop obesity and diabetes in later life. PMID:21954419

  15. Trans and interesterified fat and palm oil during the pregnancy and lactation period inhibit the central anorexigenic action of insulin in adult male rat offspring.

    PubMed

    Bispo, Kenia Pereira; de Oliveira Rodrigues, Letícia; da Silva Soares de Souza, Érica; Mucci, Daniela; Tavares do Carmo, Maria das Graças; de Albuquerque, Kelse Tibau; de Carvalho Sardinha, Fatima Lucia

    2015-01-01

    Palm oil and interesterified fat have been used to replace partially hydrogenated fats, rich in trans isomers, in processed foods. This study investigated whether the maternal consumption of normolipidic diets containing these lipids affects the insulin receptor and Akt/protein kinase B (PKB) contents in the hypothalamus and the hypophagic effect of centrally administered insulin in 3-month-old male offspring. At 90 days, the intracerebroventricular injection of insulin decreased 24-h feeding in control rats but not in the palm, interesterified or trans groups. The palm group exhibited increases in the insulin receptor content of 64 and 69 % compared to the control and trans groups, respectively. However, the quantifications of PKB did not differ significantly across groups. We conclude that the intake of trans fatty acid substitutes during the early perinatal period affects food intake regulation in response to centrally administered insulin in the young adult offspring; however, the underlying mechanisms remain unclear.

  16. Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behaviour in adult male rat offspring.

    PubMed

    Götz, Alexander A; Stefanski, Volker

    2007-01-30

    Exposure to prenatal stress can impair the behavioural and hormonal development in mammals. However, the consequences for the immune system are rarely investigated and there is only limited evidence that naturalistic prenatal stressors do also have the potential to affect the offspring. Thus, by using a social conflict model in female Long-Evans rats, we investigated the effects of prenatal social stress on several behavioural, hormonal and immunological parameters. Offspring from stressed and non-stressed pregnant females were housed in pairs after weaning, and tested at an age of 4-6 months. Prenatally stressed (PS) males were more active in the elevated plus-maze test as indicated by significantly more frequent entries into the open arms compared to prenatal control males (PC). In addition, PS males had significantly lower serum corticosterone concentrations under basal conditions as well as after ACTH-challenge. The basal number of total leukocytes was significantly lower in the PS group due to significantly lower lymphocyte counts. In particular, the CD4+ T-helper cell subset was affected. The lymphocyte proliferation to pokeweed mitogen was lower in PS males. Because some of the present findings do not correspond to previous studies using conventional stressors, we assume that the nature of the stressor plays an important role for pregnancy outcome and behaviour and physiology of the offspring in later life.

  17. Chronic exposure to cigarette smoke during gestation results in altered cholinesterase enzyme activity and behavioral deficits in adult rat offspring: potential relevance to schizophrenia.

    PubMed

    Zugno, Alexandra I; Fraga, Daiane B; De Luca, Renata D; Ghedim, Fernando V; Deroza, Pedro F; Cipriano, Andreza L; Oliveira, Mariana B; Heylmann, Alexandra S A; Budni, Josiane; Souza, Renan P; Quevedo, João

    2013-06-01

    Prenatal cigarette smoke exposure (PCSE) has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. The present study investigated locomotor activity and cholinesterase enzyme activity in rats, following PCSE and/or ketamine treatment in adulthood. Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day for a period of 28 days. We evaluated motor activity and cholinesterase activity in the brain and serum of adult male offspring that were administered acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg), which serves as an animal model of schizophrenia. To determine locomotor activity, we used the open field test. Cholinesterase activity was assessed by hydrolysis monitored spectrophotometrically. Our results show that both PCSE and ketamine treatment in the adult offspring induced increase of locomotor activity. Additionally, it was observed increase of acetylcholinesterase and butyrylcholinesterase activity in the brain and serum, respectively. We demonstrated that animals exposed to cigarettes in the prenatal period had increased the risk for psychotic symptoms in adulthood. This also occurs in a dose-dependent manner. These changes provoke molecular events that are not completely understood and may result in abnormal behavioral responses found in neuropsychiatric disorders, such as schizophrenia.

  18. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to {delta}{sup 9}-tetrahydrocannabinol

    SciTech Connect

    Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

    2007-08-15

    The present study evaluated the consequences of perinatal {delta}{sup 9}-tetrahydrocannabinol ({delta}{sup 9}-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB{sub 1} receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with {delta}{sup 9}-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, {delta}{sup 9}-THC, or EtOH + {delta}{sup 9}-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to {delta}{sup 9}-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB{sub 1} receptor antagonists may represent interesting

  19. Gestational N-hexane inhalation alters the expression of genes related to ovarian hormone production and DNA methylation states in adult female F1 rat offspring.

    PubMed

    Li, Hong; Zhang, Chenyun; Ni, Feng; Guo, Suhua; Wang, Wenxiang; Liu, Jing; Lu, Xiaoli; Huang, Huiling; Zhang, Wenchang

    2015-12-15

    Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes.

  20. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    PubMed

    Cunha, Fábio da Silva; Dalle Molle, Roberta; Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

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

    PubMed

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

    2013-11-01

    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.

  2. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

    PubMed Central

    Burns, S P; Desai, M; Cohen, R D; Hales, C N; Iles, R A; Germain, J P; Going, T C; Bailey, R A

    1997-01-01

    Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-h- starved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region. PMID:9312176

  3. Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.

    PubMed

    Li, Min; Li, Xiaobai; Zhang, Xinxin; Ren, Jintao; Jiang, Han; Wang, Yan; Ma, Yuchao; Cheng, Wenwen

    2014-06-01

    Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.

  4. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

    PubMed Central

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-01-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

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

    PubMed Central

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

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

  6. The influence of hypoxia during different pregnancy stages on cardiac collagen accumulation in the adult offspring.

    PubMed

    Wang, Lingxing; Li, Meimei; Huang, Ziyang; Wang, Zhenhua

    2014-01-01

    We evaluated whether the timing of maternal hypoxia during pregnancy influenced cardiac extracellular matrix accumulation in the adult offspring. Rats in different periods of pregnancy were assigned to maternal hypoxia or control groups. Maternal hypoxia from day 3 to 21 of pregnancy or day 9 to 21 of pregnancy increased collagen I and collagen III expression in the left ventricle of adult offspring (both P<0.05). Maternal hypoxia from day 15 to 21 of pregnancy had no effect on adult collagen levels. Our results indicate that maternal hypoxia at critical windows of cardiovascular development can induce pathological cardiac remodeling in the adult rat offspring.

  7. Aluminium and Acrylamide Disrupt Cerebellum Redox States, Cholinergic Function and Membrane-Bound ATPase in Adult Rats and Their Offspring.

    PubMed

    Ghorbel, Imen; Amara, Ibtissem Ben; Ktari, Naourez; Elwej, Awatef; Boudawara, Ons; Boudawara, Tahia; Zeghal, Najiba

    2016-12-01

    Accumulation of aluminium and acrylamide in food is a major source of human exposure. Their adverse effects are well documented, but there is no information about the health problems arising from their combined exposure. The aim of the present study was to examine the possible neurotoxic effects after co-exposure of pregnant and lactating rats to aluminium and acrylamide in order to evaluate redox state, cholinergic function and membrane-bound ATPases in the cerebellum of adult rats and their progeny. Pregnant female rats have received aluminium (50 mg/kg body weight) via drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination from the 14th day of pregnancy until day 14 after delivery. Exposure to these toxicants provoked an increase in malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels and a decrease in SOD, CAT, GPx, Na(+)K(+)-ATPase, Mg(2+)-ATPase and AChE activities in the cerebellum of mothers and their suckling pups. A reduction in GSH, NPSH and vitamin C levels was also observed. These changes were confirmed by histological results. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in the cerebellum of mothers and their progeny.

  8. PRENATAL COCAINE EXPOSURE DIFFERENTIALLY CAUSES VASCULAR DYSFUNCTION IN ADULT OFFSPRING

    PubMed Central

    Xiao, DaLiao; Huang, Xiaohui; Xu, Zhice; Yang, Shumei; Zhang, Lubo

    2009-01-01

    Epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of cardiovascular diseases and hypertension in adult life. The present study tested the hypothesis that prenatal cocaine exposure causes reprogramming of vascular reactivity, leading to an increased risk of hypertension in adult offspring. Pregnant rats received cocaine (30 mgkg-1day-1) or saline from days 15 to 21 of gestational age and experiments were conducted in 3-month-old offspring. Cocaine had no effect on the baseline blood pressure, but significantly increased norepinephrine-stimulated blood pressure and decreased the baroreflex sensitivity in male but not female offspring. The cocaine treatment significantly increased norepinephrine-induced contractions in pressurized resistance-sized mesenteric arteries but not in aortas, which was primarily due to a loss of eNOS-mediated inhibition and an enhanced Ca2+ sensitivity in mesenteric arteries. Additionally, the cocaine treatment significantly attenuated the endothelium-dependent relaxation in mesenteric arteries in male but not female offspring. eNOS protein levels in aortas but not mesenteric arteries were significantly increased in the cocaine-treated animals. However, cocaine significantly decreased phosphorylation levels of eNOS in both aortas and mesenteric arteries. The results suggest that prenatal cocaine exposure programs vascular contractility via changes in eNOS-regulated Ca2+ sensitivity of myofilaments in the sex- and tissue-dependent manners in resistance arteries leading to an increased risk of hypertension in male offspring. PMID:19380615

  9. Effects of exposure to a cafeteria diet during gestation and after weaning on the metabolism and body weight of adult male offspring in rats.

    PubMed

    Mucellini, Amanda Brondani; Goularte, Jéferson Ferraz; de Araujo da Cunha, Ana Carla; Caceres, Rafael Corrêa; Noschang, Cristie; da Silva Benetti, Carla; Silveira, Patrícia Pelufo; Sanvitto, Gilberto Luiz

    2014-04-28

    In the present study, we investigated whether maternal exposure to a cafeteria diet affects the metabolism and body composition of offspring and whether such an exposure has a cumulative effect during the lifetime of the offspring. Female rats were fed a control (CON) or a cafeteria (CAF) diet from their own weaning to the weaning of their offspring. At 21 d of age, male offspring were divided into four groups by diet during gestation and after weaning (CON-CON, CON-CAF, CAF-CON and CAF-CAF). Blood was collected from dams (after weaning) and pups (at 30 and 120 d of age) by decapitation. CAF dams had significantly greater body weight and adipose tissue weight and higher concentrations of total cholesterol, insulin and leptin than CON dams (Student's t test). The energy intake of CAF rats was higher than that of CON rats regardless of the maternal diet (two-way ANOVA). Litters had similar body weights at weaning and at 30 d of age, but at 120 d, CON-CAF rats were heavier. At both ages, CAF rats had greater adipose tissue weight than CON rats regardless of the maternal diet, and the concentrations of TAG and cholesterol were similar between the two groups, as were blood glucose concentrations at 30 d of age. However, at 120 d of age, CAF rats were hyperglycaemic, hyperinsulinaemic and hyperleptinaemic regardless of the maternal diet. These findings suggest that maternal obesity does not modulate the metabolism of male offspring independently, modifying body weight only when associated with the intake of a cafeteria diet by the offspring.

  10. The effects of co-administration of opium and morphine with nicotine during pregnancy on spatial learning and memory of adult male offspring rats

    PubMed Central

    Sepehri, Gholamreza; Parsania, Shahrnaz; Hajzadeh, Mousa-Al-Reza; Haghpanah, Tahereh; Sheibani, Vahid; Divsalar, Kouros; Shekarforoush, Shahnaz; Afarinesh, Mohammad Reza

    2014-01-01

    Objective(s): Smoking opium/cigarette is a global health concern. The aim of this study was to examine learning and memory of rat male offsprings whose mothers had been exposed to either opium or morphine with nicotine during pregnancy. Materials and Methods: Wistar rats were used for the experiments. In the female rats, opium, morphine and nicotine dependencies were induced by daily injections of drug solution for 10 days before mating. Spatial memory was tested by Morris water maze test in male pups at the postnatal day 60. The duration that took until the rats found the platform in the maze and also their swimming speed were recorded. Results: An increase in the platform finding duration was observed for the pups of dependent mothers in comparison with the control in the training trial (P<0.05). Prenatal exposure to opium/morphine and nicotine significantly decreased the time spent in the trigger zone to find the hidden platform (P<0.05) but had no significant effect on the swimming speed in the probe test. However, no significant difference was observed in the learning and memory behavior of offspring whose mothers received morphine, opium, nicotine or the co-administration of either morphine or opium with nicotine. Conclusion: The present study showed that the opium, morphine and nicotine abuse and co-administration of opium/morphine with nicotine during pregnancy may cause deficits in spatial learning of male rat offspring. Based on our data, no synergistic effects of co-drug administration were observed on learning and memory in male rat offspring. PMID:25691947

  11. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    PubMed

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-28

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  12. Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats.

    PubMed

    Zhang, Xiaosong; Wang, Qi; Wang, Yan; Hu, Jingmin; Jiang, Han; Cheng, Wenwen; Ma, Yuchao; Liu, Mengxi; Sun, Anji; Zhang, Xinxin; Li, Xiaobai

    2016-12-01

    Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions.

  13. Pregnant growth restricted female rats have bone gains during late gestation which contributes to second generation adolescent and adult offspring having normal bone health.

    PubMed

    Anevska, Kristina; Gallo, Linda A; Tran, Melanie; Jefferies, Andrew J; Wark, John D; Wlodek, Mary E; Romano, Tania

    2015-05-01

    Low birth weight, due to uteroplacental insufficiency, results in programmed bone deficits in the first generation (F1). These deficits may be passed onto subsequent generations. We characterized the effects of being born small on maternal bone health during pregnancy; and aimed to characterize the contribution of the maternal environment and germ line effects to bone health in F2 offspring from mothers born small. Bilateral uterine vessel ligation (or sham) surgery was performed on female F0 WKY rats on gestational day 18 (term 22days) to induce uteroplacental insufficiency and fetal growth restriction. Control and Restricted F1 female offspring were allocated to a non-pregnant or pregnant group. To generate F2 offspring, F1 females were allocated to either non-embryo or embryo transfer groups. Embryo transfer was performed on gestational day 1, where second generation (F2) embryos were gestated (donor-in-recipient) in either a Control (Control-in-Control, Restricted-in-Control) or Restricted (Control-in-Restricted, Restricted-in-Restricted) mother. Restricted F1 females were born 10-15% lighter than Controls. Restricted non-pregnant females had shorter femurs, reduced trabecular and cortical bone mineral contents, trabecular density and bone geometry measures determined by peripheral quantitative computed tomography (pQCT) compared to non-pregnant Controls. Pregnancy restored the bone deficits that were present in F1 Restricted females. F2 non-embryo transfer male and female offspring were born of normal weight, while F2 embryo transfer males and females gestated in a Control mother (Control-in-Control, Restricted-in-Control) were heavier at birth compared to offspring gestated in a Restricted mother (Restricted-in-Restricted, Control-in-Restricted). Male F2 Restricted embryo groups (Restricted-in-Control and Restricted-in-Restricted) had accelerated postnatal growth. There was no transmission of bone deficits present at 35days or 6months in F2 offspring. Embryo

  14. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    PubMed

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans.

  15. Gestational exercise protects adult male offspring from high-fat diet induced hepatic steatosis

    PubMed Central

    Sheldon, Ryan D.; Blaize, A. Nicole; Fletcher, Justin A.; Pearson, Kevin J.; Donkin, Shawn; Newcomer, Sean C.; Rector, R. Scott

    2015-01-01

    Background & Aims Mounting evidence indicates that maternal exercise confers protection to adult offspring against various diseases. Here we hypothesized that maternal exercise during gestation would reduce high fat diet (HFD) induced hepatic steatosis in adult rat offspring. Methods Following conception, pregnant dams were divided into either voluntary wheel running exercise (GE) or wheel-locked sedentary (GS) groups throughout gestation (days 4-21). Post-weaning, offspring received either normal chow diet (ND; 10% fat, 70% carbohydrate, 20% protein) or high-fat diet (HFD; 45% fat, 35% carbohydrate, and 20% protein) until sacrifice at 4-or 8-months of age. Results GE did not affect offspring birth weight or litter size. HFD feeding in offspring increased weight gain, % body fat, and glucose tolerance test area under the curve (GTT-AUC). Male offspring from GE dams had reduced % body fat across all ages (p < 0.05). In addition, 8-mo male offspring from GE dams were protected against HFD-induced hepatic steatosis, which was associated with increased markers of hepatic mitochondrial biogenesis (PGC-1α and TFAM), autophagic potential (ATG12:ATG5 conjugation) and hepatic triacylglycerol secretion (MTTP). Conclusions The current study provides the first evidence that gestational exercise can reduce susceptibility to high fat diet induced hepatic steatosis in adult male offspring. PMID:26325536

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

    PubMed

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

    2015-02-14

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

  17. Perinatal exercise improves glucose homeostasis in adult offspring

    PubMed Central

    Carter, Lindsay G.; Lewis, Kaitlyn N.; Wilkerson, Donald C.; Tobia, Christine M.; Ngo Tenlep, Sara Y.; Shridas, Preetha; Garcia-Cazarin, Mary L.; Wolff, Gretchen; Andrade, Francisco H.; Charnigo, Richard J.; Esser, Karyn A.; Egan, Josephine M.; de Cabo, Rafael

    2012-01-01

    Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring. PMID:22932781

  18. Perinatal exercise improves glucose homeostasis in adult offspring.

    PubMed

    Carter, Lindsay G; Lewis, Kaitlyn N; Wilkerson, Donald C; Tobia, Christine M; Ngo Tenlep, Sara Y; Shridas, Preetha; Garcia-Cazarin, Mary L; Wolff, Gretchen; Andrade, Francisco H; Charnigo, Richard J; Esser, Karyn A; Egan, Josephine M; de Cabo, Rafael; Pearson, Kevin J

    2012-10-15

    Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring.

  19. OXIDATIVE STRESS CONTRIBUTES TO SEX DIFFERENCES IN BLOOD PRESSURE IN ADULT GROWTH RESTRICTED OFFSPRING

    PubMed Central

    Ojeda, Norma B.; Hennington, Bettye Sue; Williamson, Danielle T.; Hill, Melanie L.; Betson, Nicole E.E.; Sartori-Valinotti, Julio C.; Reckelhoff, Jane F.; Royals, Thomas P.; Alexander, Barbara T.

    2013-01-01

    Numerous experimental studies suggest that oxidative stress contributes to the pathophysiology of hypertension and importantly, that oxidative stress plays a more definitive role in mediating hypertension in males than in females. Intrauterine growth-restriction induced by reduced uterine perfusion initiated at day 14 of gestation in the rat programs hypertension in adult male growth-restricted offspring; yet, female growth-restricted offspring are normotensive. The mechanisms mediating sex differences in blood pressure in adult growth-restricted offspring are not clear. Thus, this study tested the hypothesis that sex specific differences in renal oxidative stress contribute to the regulation of blood pressure in adult growth-restricted offspring. A significant increase in blood pressure measured by telemetry in male growth-restricted offspring (P<0.05) was associated with a marked increase in renal markers of oxidative stress (P<0.05). Chronic treatment with the antioxidant tempol had no effect on blood pressure in male control offspring, but it normalized blood pressure (P<0.05) and renal markers of oxidative stress (P<0.05) in male growth-restricted relative to male control. Renal markers of oxidative stress were not elevated in female growth-restricted offspring; however, renal activity of the antioxidant catalase was significantly elevated relative to female control (P<0.05). Chronic treatment with tempol did not significantly alter oxidative stress or blood pressure measured by telemetry in female offspring. Thus, these data suggest that sex differences in renal oxidative stress and antioxidant activity are present in adult growth-restricted offspring, and that oxidative stress may play a more important role in modulating blood pressure in male, but not female growth-restricted offspring. PMID:22585945

  20. Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring

    PubMed Central

    Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L. H.; Leu, Steve; Chan, Julie Y. H.

    2016-01-01

    Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE. PMID:27703194

  1. Perceived parental control in childhood and sexual preferences of adult offspring.

    PubMed

    Khaleque, Abdul

    2003-06-01

    To assess the relation between perceived parental control during childhood and sexual preferences of offspring during adulthood, 80 adult offspring of heterosexual orientation reported significantly lower parental control during childhood than 7 adult offspring with nonheterosexual orientation.

  2. Early free access to hypertonic NaCl solution induces a long-term effect on drinking, brain cell activity and gene expression of adult rat offspring.

    PubMed

    Macchione, A F; Beas, C; Dadam, F M; Caeiro, X E; Godino, A; Ponce, L F; Amigone, J L; Vivas, L

    2015-07-09

    Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. The manipulation (M) period covered dams from 1 week before conception until offspring turned 1-month-old. The experimental groups were (i) Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative water intake (140 min) and drinking latency to the first lick were recorded from the start of the infusion. Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.

  3. Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring.

    PubMed

    Konycheva, Galina; Dziadek, Marie A; Ferguson, Lynnette R; Krägeloh, Christian U; Coolen, Marcel W; Davison, Michael; Breier, Bernhard H

    2011-10-01

    Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study.

  4. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

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

    PubMed Central

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

    2012-01-01

    Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. PMID:23300784

  6. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism.

    PubMed

    Seet, Emily L; Yee, Jennifer K; Jellyman, Juanita K; Han, Guang; Ross, Michael G; Desai, Mina

    2015-06-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway.

  7. Maternal Nutrient Restriction Predisposes Ventricular Remodeling in Adult Sheep Offspring

    PubMed Central

    Ge, Wei; Hu, Nan; George, Lindsey A.; Ford, Stephen P.; Nathanielsz, Peter W.; Wang, Xiaoming; Ren, Jun

    2012-01-01

    Maternal nutrient restriction during pregnancy is associated with the development of a “thrifty phenotype” in offspring, conferring increased prevalence of metabolic diseases in adulthood. To explore the possible mechanisms behind heart diseases in adulthood following maternal nutrient restriction, dams were fed a nutrient restricted (NR: 50%) or control (100%) diet from 28 to 78 d of gestation. Both groups were then fed 100% of requirements to lambing. At 6 yrs of age, female offspring of NR and control ewes of similar weight and body condition were subject to ad libitum feeding of a highly palatable diet for 12 wks. Cardiac geometry, post-insulin receptor signaling, autophagy and pro-inflammatory cytokines were evaluated in hearts from adult offspring. Our results indicated that maternal nutrient restriction overtly increased body weight gain and triggered cardiac remodeling in offspring following the 12-week ad libitum feeding. Phosphorylation of IRS1 was increased in left but not right ventricles from NR offspring. Levels of STAT3 were upregulated in left ventricles whereas expression of TNFα and TLR4 was enhanced in right ventricles in adult offspring of maternal nutrition restricted ewes. No significant differences were found in pan IRS-1, pan AMPK, pan Akt, pAMPK, pAkt, GLUT4, phosphorylated mTOR, Beclin-1 and LC3 II proteins in left and right ventricle between the control and NR offspring. These data revealed that maternal nutrient restriction during early to mid gestation may predispose adult offspring to cardiac remodeling possibly associated with phosphorylation of IRS1 as well as proinflammatory cytokines but not autophagy. PMID:23333094

  8. Do copper tolerant fathead minnows produce copper tolerant adult offspring?

    PubMed Central

    Kolok, Alan S.; L’Etoile-Lopes, Darcy

    2009-01-01

    The objective of this study was to determine if the relative Cu tolerance of fathead minnow parents determines the, relative Cu tolerance of their adult offspring. It was hypothesized that the adult offspring of Cu-tolerant minnows would inherit Cu tolerance from their parents. The relative Cu tolerance of 96 adult fish was determined based upon their reduction in swim performance following a sublethal exposure to 150 μg Cu/l. Control, Cu-tolerant and Cu-susceptible lines of fish were produced and fish within each line were allowed to breed. The offspring were raised to adults, then exposed to one of two sublethal Cu concentrations (150 or 225 (μg Cu/l) for 8 days. There were no significant differences in relative Cu tolerance, as measured by reduction in swim performance, among the three lines of fish at either dose. However, significant differences in whole body Na+ occurred among the fish lines after exposure to 150 μg Cu/l, but not after exposure to 225 μg Cu/l. Significant differences in whole body Cu occurred between Cu-tolerant and Cu-susceptible fish lines after exposure to either Cu dose. The offspring did not inherit the relative Cu tolerance of their parents, however, the selection lines had diverged from each other, particularly with respect to their whole body Cu concentrations after exposure. PMID:15820103

  9. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

    ERIC Educational Resources Information Center

    Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Fernandes, Jansen; Lopim, Glauber Menezes; Cabral, Francisco Romero; Scerni, Débora Amado; de Oliveira-Pinto, Ana Virgínia; Lent, Roberto; Arida, Ricardo Mario

    2016-01-01

    Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell…

  10. Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring.

    PubMed

    Bubenikova-Valesova, Vera; Kacer, Petr; Syslova, Kamila; Rambousek, Lukas; Janovsky, Martin; Schutova, Barbora; Hruba, Lenka; Slamberova, Romana

    2009-10-01

    Methamphetamine is a commonly abused psychostimulant that causes addiction and is often abused by pregnant women. Acute or chronic administration of methamphetamine elevates the levels of the extracellular monoamine neurotransmitters, such as dopamine. The aim of the present study was to show whether prenatal exposure to methamphetamine (5mg/kg, entire gestation) or saline in Wistar rats induces changes in dopamine levels and its metabolites in the nucleus accumbens, and in behavior (locomotor activity, rearing, and immobility) after the administration of a challenge dose of methamphetamine (1mg/kg) or saline in male offspring. We found that adult offspring prenatally exposed to methamphetamine had higher basal levels of dopamine (about 288%), dihydroxyphenylacetic acid (about 67%) and homovanillic acid (about 74%) in nucleus accumbens. An increased basal level of dopamine corresponds to lower basal immobility in offspring prenatally exposed to methamphetamine. The acute injection of methamphetamine in adulthood increased the level of dopamine in the nucleus accumbens, which is related to an increase of locomotion and rearing (exploration). In addition, prenatally methamphetamine-exposed rats showed higher response to the challenge dose of methamphetamine, when compared to prenatally saline-exposed rats. In conclusion, rats exposed to methamphetamine in utero have shown changes in the mesolimbic dopaminergic system and were more sensitive to the administration of the acute dose of methamphetamine in adulthood.

  11. In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

    PubMed Central

    Hanafi, Mervat Y.; Saleh, Moustafa M.; Kamel, Maher A.

    2016-01-01

    Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-α) in F1 offspring in rats. Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD) and under high-fat diet (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD) and under HCD (OF1-HCD), and F1 offspring of malnourished mothers under CD (MF1-CD) and under HCD (MF1-HCD). Every 5 weeks postnatally, blood samples were obtained for biochemical analysis. Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1-HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-α compared to CF1-CD and CF1-HCD (p < 0.05). Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production. PMID:27200209

  12. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint).

    PubMed

    Barbalho, Sandra M; Damasceno, Débora C; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M V Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications.

  13. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M. V. Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications. PMID:21647314

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2014-08-01

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

  16. Alterations in hepatic gene expression and genome-wide DNA methylation in rat offspring exposed to maternal obesity in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult offspring from obese (OB) rat dams gain greater body weight and fat mass than controls when fed HFD. At PND21, we examined energy expenditure (EE) (indirect calorimetry), hepatic gene expression (microarrays), and changes in genome-wide and global DNA methylation (enrichment-coupled DNA seque...

  17. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-08-15

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD{sub 50}; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics.

  18. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    PubMed

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-04

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission.

  19. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  20. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.

    PubMed

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-05

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  1. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    NASA Astrophysics Data System (ADS)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  2. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    PubMed Central

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  3. Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

    PubMed

    Ramírez-López, María Teresa; Arco, Raquel; Decara, Juan; Vázquez, Mariam; Noemí Blanco, Rosario; Alén, Francisco; Suárez, Juan; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

    2016-01-01

    Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS). In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a) the adult expression of endocannabinoid-related behaviors, b) the metabolic profile of adult offspring and c) the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a) sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b) features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c) tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

  4. Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring

    PubMed Central

    Ramírez-López, María Teresa; Arco, Raquel; Decara, Juan; Vázquez, Mariam; Noemí Blanco, Rosario; Alén, Francisco; Suárez, Juan; Gómez de Heras, Raquel

    2016-01-01

    Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS). In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a) the adult expression of endocannabinoid-related behaviors, b) the metabolic profile of adult offspring and c) the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a) sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b) features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c) tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed. PMID:27806128

  5. Levels of maternal care in dogs affect adult offspring temperament

    PubMed Central

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs. PMID:26758076

  6. Levels of maternal care in dogs affect adult offspring temperament.

    PubMed

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-13

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.

  7. Levels of maternal care in dogs affect adult offspring temperament

    NASA Astrophysics Data System (ADS)

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-01

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.

  8. Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring

    PubMed Central

    Voiculescu, SE; Rosca, AE; Zeca, V; Zagrean, L; Zagrean, AM

    2015-01-01

    Melatonin is an essential hormone, which regulates circadian rhythms and has antioxidative and anticarcinogenic effects. As melatonin secretion is suppressed by light, this effect was examined on the offspring of the Wistar rat females exposed to continuous light (500 lux) during the second half of the pregnancy (day 12 to 21). Control rats were kept under a 12:12 light-dark cycle. The resulted male offspring have been behaviorally assessed for depression after postnatal day 60 by using Forced Swim Test (FST) and Tail Suspension Test (TST). Animals resulted from the melatonin deprived pregnancies have developed an abnormal response in the TST, but a normal FST behavior. Also, TST active movement was different in the melatonin suppression group compared to the control group. These findings suggest that intrauterine melatonin deprivation might be linked to the depressive like behavior in adult male offspring. PMID:25866579

  9. Arsenite in drinking water produces glucose intolerance in pregnant rats and their female offspring.

    PubMed

    Bonaventura, María Marta; Bourguignon, Nadia Soledad; Bizzozzero, Marianne; Rodriguez, Diego; Ventura, Clara; Cocca, Claudia; Libertun, Carlos; Lux-Lantos, Victoria Adela

    2017-02-01

    Drinking water is the main source of arsenic exposure. Chronic exposure has been associated with metabolic disorders. Here we studied the effects of arsenic on glucose metabolism, in pregnant and post-partum of dams and their offspring. We administered 5 (A5) or 50 (A50) mg/L of sodium arsenite in drinking water to rats from gestational day 1 (GD1) until two months postpartum (2MPP), and to their offspring from weaning until 8 weeks old. Liver arsenic dose-dependently increased in arsenite-treated rats to levels similar to exposed population. Pregnant A50 rats gained less weight than controls and recovered normal weight at 2MPP. Arsenite-treated pregnant animals showed glucose intolerance on GD16-17, with impaired insulin secretion but normal insulin sensitivity; they showed dose-dependent increased pancreas insulin on GD18. All alterations reverted at 2MPP. Offspring from A50-treated mothers showed lower body weight at birth, 4 and 8 weeks of age, and glucose intolerance in adult females, probably due to insulin secretion and sensitivity alterations. Arsenic alters glucose homeostasis during pregnancy by altering beta-cell function, increasing risk of developing gestational diabetes. In pups, it induces low body weight from birth to 8 weeks of age, and glucose intolerance in females, demonstrating a sex specific response.

  10. Hyperleptinemia During Pregnancy Decreases Adult Weight of Offspring and Is Associated With Increased Offspring Locomotor Activity in Mice.

    PubMed

    Pollock, Kelly E; Stevens, Damaiyah; Pennington, Kathleen A; Thaisrivongs, Rose; Kaiser, Jennifer; Ellersieck, Mark R; Miller, Dennis K; Schulz, Laura Clamon

    2015-10-01

    Pregnant women who are obese or have gestational diabetes mellitus have elevated leptin levels and their children have an increased risk for child and adult obesity. The goals of this study were to determine whether offspring weights are altered by maternal hyperleptinemia, and whether this occurs via behavioral changes that influence energy balance. We used 2 hyperleptinemic mouse models. The first was females heterozygous for a leptin receptor mutation (DB/+), which were severely hyperleptinemic, and that were compared with wild-type females. The second model was wild-type females infused with leptin (LEP), which were moderately hyperleptinemic, and were compared with wild-type females infused with saline (SAL). Total food consumption, food preference, locomotor activity, coordinated motor skills, and anxiety-like behaviors were assessed in wild-type offspring from each maternal group at 3 postnatal ages: 4-6, 11-13, and 19-21 weeks. Half the offspring from each group were then placed on a high-fat diet, and behaviors were reassessed. Adult offspring from both groups of hyperleptinemic dams weighed less than their respective controls beginning at 23 weeks of age, independent of diet or sex. Weight differences were not explained by food consumption or preference, because female offspring from hyperleptinemic dams tended to consume more food and had reduced preference for palatable, high-fat and sugar, food compared with controls. Offspring from DB/+ dams were more active than offspring of controls, as were female offspring of LEP dams. Maternal hyperleptinemia during pregnancy did not predispose offspring to obesity, and in fact, reduced weight gain.

  11. Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

    PubMed Central

    Xiao, DaLiao; Huang, Xiaohui; Xue, Qin; Zhang, Lubo

    2014-01-01

    In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring. PMID:24905716

  12. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

    PubMed

    Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

    2012-10-01

    The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

  13. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    PubMed

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms.

  14. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    PubMed

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation.

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

    PubMed Central

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

    2015-01-01

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

  16. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    PubMed Central

    de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

    2015-01-01

    Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

  17. Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; Palhares, Miréia; Martuchi, Karla Aparecida; Oshiiwa, Marie; Sazaki, Viviane; da Silva, Vanessa Sellis

    2011-01-01

    Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola) juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams) treated with water, G2, offspring (of diabetic dams) treated with water, G3, male offspring (of control dams) treated with acerola juice, and G4, male offspring (of diabetic dams) treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases. PMID:21318139

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Maternal protein intake in the pregnant rat programs the insulin axis and body composition in the offspring.

    PubMed

    Rees, William D; Hay, Susan M; Cruickshank, Morven; Reusens, Brigitte; Remacle, Claude; Antipatis, Christos; Grant, George

    2006-05-01

    Evidence to support an association between early nutrition and the development of obesity in the rat is equivocal. In this study we have investigated the postnatal growth, glucose tolerance, and adipocyte function of the offspring from pregnant rats fed with diets containing either 20% or 8% protein during gestation. By 25 weeks of age, the female offspring of dams fed with the diet containing 8% protein had a significantly lower adult body weight due in part to a decrease in body fat. The peak concentration of insulin after oral administration of a glucose dose was significantly lower in both the male and female offspring of the dams fed with the diet containing 8% protein. However, the ability of insulin to stimulate lipogenesis or suppress lipolysis in fat cells isolated from the offspring was not influenced by the prenatal diet. Hepatic phosphoenolpyruvate carboxykinase activity was reduced in female offspring of dams fed with the diet containing 8% protein. These results show that adult body composition is determined during the prenatal period as a result of programming of the insulin axis. This metabolic programming influences hepatic metabolism; however, there is no evidence for a programmed change in adipocyte function.

  20. Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

    PubMed Central

    Gao, Xin; Sun, Lvhui; Zhang, Niya; Li, Chong; Zhang, Jiacai; Xiao, Zhuohui; Qi, Desheng

    2017-01-01

    Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3β-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females. PMID:28067781

  1. Effects of ethanol on pregnant rats and their offspring.

    PubMed

    Abel, E L

    1978-04-14

    Pregnant rats were intubated with either 1.0 or 2.0 g/kg of ethanol daily throughout gestation. Pair-fed vehicle-treated, and nontreated rats fed ad libitum, served as control groups for ethanol-treated animals. Ethanol treatment reduced food and water consumption and attenuated the gain in body weight of pregnant animals relative to nontreated animals fed ad libitum. Litter size, litter weight, and the mean weight per pup were reduced in both the ethanol-treated and pair-fed control groups. There was no evidence of gross malformations in any of the off-spring. Since the reduction in litter size and litter weights did not differ significantly between ethanol-treated and pair-fed controls, the effects of treatment with ethanol appeared to be related to a reduction in maternal intake of calories rather than to the direct effect of ethanol on the developing fetus. There were no significant differences between any of the groups of offspring on one-way shock avoidance learning, water maze escape learning, spontaneous alternation, or brightness discrimination learning in tests beginning at 75 days of age. Thus, at the doses of alcohol used in this study, there was no evidence of behavioral teratogenesis comparable to that reported for higher doses in animals or in man characterized by the fetal alcohol syndrome.

  2. Autobiographical memory in adult offspring of traumatized parents with and without posttraumatic stress symptoms.

    PubMed

    Wittekind, Charlotte E; Jelinek, Lena; Moritz, Steffen; Muhtz, Christoph; Berna, Fabrice

    2016-08-30

    The present study examined potential transgenerational effects of trauma on autobiographical memory in adult offspring of elderly participants with and without PTSD symptoms who were exposed to an early trauma during childhood. As traumatization is associated with reduced memory specificity for past events, we hypothesized that offspring of traumatized parents might be exposed to a less elaborative narrative style, which, in turn, might result in less specific autobiographical memories in the offspring. Results show that autobiographical memory specificity did not differ significantly between adult offspring of traumatized elderly participants with PTSD symptoms, without PTSD symptoms, and non-traumatized elderly participants.

  3. Maternal Omega-3 Supplementation Increases Fat Mass in Male and Female Rat Offspring

    PubMed Central

    Muhlhausler, Beverly Sara; Miljkovic, Dijana; Fong, Laura; Xian, Cory J.; Duthoit, Emmanuelle; Gibson, Robert A.

    2011-01-01

    Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA) inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n = 10) or chow designed to provide ∼15 mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA), throughout pregnancy and lactation (Omega-3, n = 11) and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3 and 6 weeks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using quantitative real time reverse transcription-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 ± 0.32% vs. 4.56 ± 0.2%, P < 0.04) and female (5.15 ± 0.37% vs. 3.89 ± 0.36%, P < 0.04) offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a% of total fatty acids) was higher in omega-3 offspring (6.7 ± 0.2% vs. 5.6 ± 0.2%, P < 0.001). There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n−3 LCPUFA

  4. Preweaning GH Treatment Normalizes Body Growth Trajectory and Reverses Metabolic Dysregulation in Adult Offspring After Maternal Undernutrition.

    PubMed

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

    2015-09-01

    Maternal undernutrition (UN) results in growth disorders and metabolic dysfunction in offspring. Although dysregulation of the GH-IGF axis in offspring is a known consequence of maternal UN, little is known about the efficacy of GH treatment during the period of developmental plasticity on later growth and metabolic outcomes. The present study investigated the effect of preweaning GH treatment on growth, glucose metabolism, and the GH-IGF axis in adult male and female offspring after maternal UN. Female Sprague Dawley rats were fed either a chow diet ad libitum (control [CON]) or 50% of ad libitum (UN) throughout pregnancy. From postnatal day 3, CON and UN pups received either saline (CON-S and UN-S) or GH (2.5 μg/g·d CON-GH and UN-GH) daily throughout lactation. At weaning, male and female offspring were randomly selected from each litter and fed a standard chow diet for the remainder of the study. Preweaning GH treatment normalized maternal UN-induced alterations in postweaning growth trajectory and concomitant adiposity in offspring. Plasma leptin concentrations were increased in UN-S offspring and normalized in the UN-GH group. Hepatic GH receptor expression was significantly elevated in UN-S offspring and normalized with GH treatment. Hepatic IGF binding protein-2 gene expression and plasma IGF-1 to IGF binding protein-3 ratio was reduced in UN-S offspring and elevated with GH treatment. GH treatment during a critical developmental window prevented maternal UN-induced changes in postnatal growth patterns and related adiposity, suggesting that manipulation of the GH-IGF-1 axis in early development may represent a promising avenue to prevent adverse developmental programming effects in adulthood.

  5. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    PubMed

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

  6. Comparison of the effects of fetal hypothyroidism on glucose tolerance in male and female rat offspring.

    PubMed

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Zahediasl, Saleh; Ghasemi, Asghar

    2015-03-01

    Thyroid hormones are vital for survival of mammalian species and play critical roles in growth, development, and metabolism. Both fetal hypothyroidism and sex can affect carbohydrate metabolism during adult life. This study aims to assess carbohydrate metabolism in male and female offspring born from mothers who were hypothyroid during pregnancy. Pregnant rats were divided into two groups; the controls consumed water and the hypothyroid group received water containing 0.025 % 6-propyl-2-thiouracial throughout gestation. The intravenous glucose tolerance test (0.5 g/kg glucose) was carried out in 3-month-old offspring. Findings showed that compared to controls, male fetal hypothyroid rats during adulthood had glucose intolerance (area under the curve: 446.4 ± 9.7 vs. 486.4 ± 8.8, p < 0.01 in control and fetal hypothyroid groups, respectively) whereas females had improved glucose tolerance (478.1 ± 7.0 vs. 455.9 ± 8.5, p < 0.01). In conclusion, sex could modulate the effects of fetal hypothyroidism on glucose tolerance in rats.

  7. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

    PubMed

    Miranda-Spooner, M; Paccola, C C; Neves, F M O; de Oliva, S U; Miraglia, S M

    2016-03-01

    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.

  8. Parental Depression as a Moderator of Secondary Deficits of Depression in Adult Offspring

    ERIC Educational Resources Information Center

    Timko, Christine; Cronkite, Ruth C.; Swindle, Ralph; Robinson, Rebecca L.; Sutkowi, Anne; Moos, Rudolf H.

    2009-01-01

    This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed…

  9. Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

    PubMed Central

    de Queiroz, D B; Sastre, E; Caracuel, L; Callejo, M; Xavier, F E; Blanco-Rivero, J; Balfagón, G

    2015-01-01

    Background and Purpose We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. Experimental Approach Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. Key Results Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. Conclusions and Implications The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats. PMID:26177571

  10. Dietary flax oil during pregnancy and lactation retards disease progression in rat offspring with inherited kidney disease.

    PubMed

    Sankaran, Deepa; Bankovic-Calic, Neda; Peng, Claudia Yu-Chen; Ogborn, Malcolm R; Aukema, Harold M

    2006-12-01

    Dietary flax oil (FO) retards disease progression in growing or adult animal models of kidney disease. To determine whether dietary flax oil during the perinatal period would alter renal disease progression in offspring, Han-SPRD-cy rats with inherited cystic kidney disease were given diets with either 7% FO or corn oil (CO), throughout pregnancy and lactation. At 3 wk of age, offspring were then given either the same or the alternate diet for 7 wk. Rats given FO during the maternal period had 15% less renal cyst growth compared with rats given FO only in the postweaning period. Dietary FO, compared with CO, in the maternal period also resulted in 12% lower cell proliferation and 15% less oxidant injury in diseased kidneys of offspring. Including FO in both the maternal and postweaning period resulted in 29-34% less renal interstitial fibrosis and 22-23% lower glomerular hypertrophy. Along with improved histology, these rats exhibited 13% less proteinuria and 30% lower creatinine clearance when dietary FO was given in the maternal period. The potential for dietary FO during pregnancy and lactation to positively modulate adult renal disease has significant implications for the 1 in 1000 individuals with congenital cystic kidney disease.

  11. Maternal exposure to diets containing high fructose and saturated fats, low B vitamins, or their combination programs growth, adiposity, and insulin sensitivity in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early exposure to unfavorable nutrition programs increases risk of adult-onset diseases. In this rat study, we investigate morphological, metabolic and endocrinal phenotypes of offspring born to dams consuming isocaloric diets containing 30% fructose, 9.9% coconut fat and 0.5% cholesterol (F+SFA), m...

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

    PubMed Central

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

    2015-01-01

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

  13. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure.

    PubMed

    Nobre, J L; Lisboa, P C; Santos-Silva, A P; Lima, N S; Manhães, A C; Nogueira-Neto, J F; Cabanelas, A; Pazos-Moura, C C; Moura, E G; de Oliveira, E

    2011-09-01

    Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. Mothers Do Not Show Increased Offspring Avoidance and Elevated Corticosterone Levels during Weaning Conflict in Rats

    PubMed Central

    Cox, Charlotte; Hager, Reinmar

    2016-01-01

    Parent-offspring conflict is predicted to occur because offspring will demand more parental investment than is optimal for the parent, and is said to be strongest during weaning when parents reduce nursing while offspring continue to demand parental care. While weaning conflict has been shown to be stressful in offspring, little is known about the effects of weaning conflict on mothers. We hypothesized that during weaning mothers have higher levels of stress hormone (corticosterone) compared to early lactation because of increased offspring demand. Further, we predicted that if mothers are given the option to avoid offspring solicitation they would do so and show lower corticosterone levels. We tested our hypotheses in an experimental population of rats in which one group of females was given the opportunity to avoid offspring solicitation. We measured faecal corticosterone metabolite levels using a non-invasive approach, and maternal and offspring behaviours during weaning. In contrast to our predictions, we detected lower levels of corticosterone metabolites during weaning than before, irrespective of cage type. Further, during weaning mothers did not show increased offspring avoidance behaviour although offspring solicitation increased significantly. Our results therefore cast doubt on the generally accepted notion of weaning conflict as a stressful period for mothers characterized by overt offspring solicitation. PMID:27662366

  16. Effect of maternal diabetes on longevity in offspring of spontaneously hypertensive rats.

    PubMed

    Iwase, M; Wada, M; Shinohara, N; Yoshizumi, H; Yoshinari, M; Fujishima, M

    1995-01-01

    We studied the effect of maternal diabetes induced by neonatal streptozotocin treatment on the longevity of the male offspring in spontaneously hypertensive rats (SHR). Maternal diabetes significantly decreased the survival in the offspring as compared with the control (p < 0.01). Mean age at death was 14.9 +/- 0.6 months in the offspring from the diabetic dams and 17.9 +/- 1.1 months in that from the control. The life span was significantly correlated with the birth weight (rs = 0.55, p = 0.009). These findings suggest that a diabetic pregnancy may accelerate an age-related degenerative process of the offspring in SHR.

  17. Mothers' exercise during pregnancy programs vasomotor function in adult offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intrauterine environment is influenced by maternal behavior and known to influence lifelong atherosclerotic disease susceptibility in offspring. The purpose of this investigation was to test the hypothesis that maternal exercise during pregnancy increases endothelial function in offs...

  18. Associations of parental age with health and social factors in adult offspring. Methodological pitfalls and possibilities.

    PubMed

    Carslake, David; Tynelius, Per; van den Berg, Gerard; Davey Smith, George; Rasmussen, Finn

    2017-03-27

    Parental age is increasing rapidly in many countries. Analysis of this potentially important influence on offspring well-being is hampered by strong secular trends and socioeconomic patterning and by a shortage of follow-up data for adult offspring. We used Swedish national data on up to 3,653,938 offspring to consider the associations of parental age with a suite of outcomes in adult offspring, comparing the results from an array of statistical methods for optimal causal inference. The offspring of older mothers had higher BMI, blood pressure, height, intelligence, non-cognitive ability and socioeconomic position. They were less likely to smoke or to be left-handed. Associations with paternal age were strongly, but not completely, attenuated by adjustment for maternal age. Estimates from the commonly-used sibling comparison method were driven primarily by a pathway mediated by offspring date of birth when outcomes showed strong secular trends. These results suggest that the intra-uterine and early life environments provided by older mothers may be detrimental to offspring cardiovascular health, but that their greater life experience and social position may bring intellectual and social advantages to their offspring. The analysis of parental age presents particular challenges, and further methodological developments are needed.

  19. Associations of parental age with health and social factors in adult offspring. Methodological pitfalls and possibilities

    PubMed Central

    Carslake, David; Tynelius, Per; van den Berg, Gerard; Davey Smith, George; Rasmussen, Finn

    2017-01-01

    Parental age is increasing rapidly in many countries. Analysis of this potentially important influence on offspring well-being is hampered by strong secular trends and socioeconomic patterning and by a shortage of follow-up data for adult offspring. We used Swedish national data on up to 3,653,938 offspring to consider the associations of parental age with a suite of outcomes in adult offspring, comparing the results from an array of statistical methods for optimal causal inference. The offspring of older mothers had higher BMI, blood pressure, height, intelligence, non-cognitive ability and socioeconomic position. They were less likely to smoke or to be left-handed. Associations with paternal age were strongly, but not completely, attenuated by adjustment for maternal age. Estimates from the commonly-used sibling comparison method were driven primarily by a pathway mediated by offspring date of birth when outcomes showed strong secular trends. These results suggest that the intra-uterine and early life environments provided by older mothers may be detrimental to offspring cardiovascular health, but that their greater life experience and social position may bring intellectual and social advantages to their offspring. The analysis of parental age presents particular challenges, and further methodological developments are needed. PMID:28345590

  20. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    SciTech Connect

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  1. The Effects of Parental Health Shocks on Adult Offspring Smoking Behavior and Self-Assessed Health.

    PubMed

    Darden, Michael; Gilleskie, Donna

    2016-08-01

    An important avenue for smoking deterrence may be through familial ties if adult smokers respond to parental health shocks. In this paper, we merge the Original Cohort and the Offspring Cohort of the Framingham Heart Study to study how adult offspring smoking behavior and subjective health assessments vary with elder parent smoking behavior and health outcomes. These data allow us to model the smoking behavior of adult offspring over a 30-year period contemporaneously with parental behaviors and outcomes. We find strong 'like father, like son' and 'like mother, like daughter' correlations in smoking behavior. We find that adult offspring significantly curtail their own smoking following an own health shock; however, we find limited evidence that offspring smoking behavior is sensitive to parent health, with the notable exception that women significantly reduce both their smoking participation and intensity following a smoking-related cardiovascular event of a parent. We also model the subjective health assessment of adult offspring as a function of parent health, and we find that women report significantly worse health following the smoking-related death of a parent. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Parental divorce, parental depression, and gender differences in adult offspring suicide attempt.

    PubMed

    Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

    2009-12-01

    Research suggests parental divorce during childhood increases risk of suicide attempt for male but not female offspring. The negative impact on offspring associated with parental divorce may be better explained by parental psychopathology, such as depression. We examined whether adult offspring of parental divorce experience elevated risk of suicide attempt, controlling for parental history of depression, and whether the risk varies by the gender of the offspring. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the sample consists of respondents who experienced parental divorce (N = 4895). Multivariable regressions controlled for age, race/ethnicity, income, marital status, and parental history of depression. Females living with their fathers were significantly more likely to report lifetime suicide attempts than females living with their mothers, even after controlling for parental depression. Findings suggest that childhood/adolescent parental divorce may have a stronger impact on suicide attempt risk in female offspring than previously recognized.

  3. Prenatal cocaine exposure causes sex-dependent impairment in the myogenic reactivity of coronary arteries in adult offspring

    PubMed Central

    Xiao, DaLiao; Yang, Shumei; Zhang, Lubo

    2009-01-01

    Cocaine abuse is a significant problem among pregnant women. The present study tested the hypothesis that prenatal cocaine exposure impairs myogenic reactivity of coronary arteries in adult offspring. Pregnant rats received cocaine (30 mg kg−1 day−1) or saline from days 15 to 21 of gestational age and experiments were conducted in 3-month-old offspring. In pressurized coronary septal arteries, the diameter and vessel wall intracellular Ca2+ concentrations were measured simultaneously in the same tissue as a function of intraluminal pressure. Cocaine did not affect KCl-induced contractions of coronary arteries in either males or females, but decreased the distensibility in male vessels. In male offspring, cocaine treatment resulted in a significant decease in pressure-dependent myogenic contractions. Inhibition of eNOS with NG-nitro-L-arginine did not alter the myogenic response in either saline control or cocaine-treated animals. In females, cocaine caused a significant increase in pressure-dependent myogenic contractions. NG-nitro-L-arginine did not affect the myogenic response in the control animals, but blocked the cocaine-mediated effect. In both males and females, the presure-induced increases in vessel wall Ca2+ concentrations were not significantly different between cocaine and saline groups. The ratio of changes in the diameter to Ca2+ concentrations in the presurized arteries was significantly less in male but greater in female offspring after cocaine treatment. The results suggest that prenatal cocaine exposure causes reprogramming of coronary myogenic tone via changes in the Ca2+ sensitivity in a sex-dependent manner, leading to an increased risk of dysfunction of coronary autoregulation in adult offspring. PMID:19704103

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

    PubMed Central

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

    2013-01-01

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

  5. Neurofunctional Evaluation of Young Male Offspring of Rat Dams with Diabetes Induced by Streptozotocin

    PubMed Central

    Delascio Lopes, Carla; Sinigaglia-Coimbra, Rita; Mazzola, Jacqueline; Camano, Luiz; Mattar, Rosiane

    2011-01-01

    Diabetes mellitus (DM) is a complex disease, being one of the most prevalent diseases worldwide. As a consequence, pregnancy-associated diabetes is increasingly common. Given the numerous studies about the influence of diabetes on offspring of diabetic rat dams, the neurological outcome is of outmost importance. This paper aimed at evaluating the neurofunctional performance of young male offspring of rat dams with diabetes induced by streptozotocin. Diabetes was induced in Wistar female rats by streptozotocin administration, while control groups received vehicle injection. At two-month survival period, male offspring from each group were randomized to the water maze Morris test, in order to assess their neurofunctional status. There was no significant difference between the groups as assessed by the Morris water maze test for spatial reference task. Our results point to the need of further investigation on the offspring neurofunctional performance. PMID:22363880

  6. Developmental delays in offspring of rats undernourished or zinc deprived during lactation.

    PubMed

    Eberhardt, M J; Halas, E S

    1987-01-01

    Offspring of rats who were zinc or calorie deprived during lactation were administered a battery of reflex and motor tests from postnatal Day 4 to Day 21. Compared to offspring of ad lib-fed control rats, both zinc deprived and undernourished offspring exhibited developmental delays in reflexes which appeared after the first postnatal week (auditory startle, air righting, and rope descent). As the deficiencies continued the delays appeared to be more pronounced. The zinc deficiency did not add to the deficits associated with calorie restriction alone because there were no significant differences between the zinc deficient and undernourished pups on any of the measures except eye opening. When rehabilitated offspring were tested at 45 and 60 days of age for motor deficits there were no significant impairments resulting from preweaning dietary conditions. However, the growth retardation of zinc deprived and undernourished rats persisted long after dietary rehabilitation was implemented.

  7. Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague-Dawley Rat Offsprings

    PubMed Central

    Choi, Inah; Kim, Pitna; Joo, So Hyun; Kim, Min Kyeong; Park, Jin Hee; Kim, Hee Jin; Ryu, Jong Hoon; Cheong, Jae Hoon; Shin, Chan Young

    2012-01-01

    Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investi-gated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat. PMID:24116300

  8. Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring

    EPA Science Inventory

    Objective: Global undernutrition, low protein diet or dexamethasone treatment during pregnancy has been demonstrated in animal models to result in adverse health effects including hypertension and insulln resistance in adult offspring. Most protocols that produce these effects ca...

  9. Maternal caloric restriction prior to pregnancy increases the body weight of the second-generation male offspring and shortens their longevity in rats.

    PubMed

    Araminaite, Violeta; Zalgeviciene, Violeta; Simkunaite-Rizgeliene, Renata; Stukas, Rimantas; Kaminskas, Arvydas; Tutkuviene, Janina

    2014-01-01

    Maternal undernutrition can affect offspring's physical status and various health parameters that might be transmittable across several generations. Many studies have focused on undernutrition throughout pregnancy, whereas maternal undernutrition prior to pregnancy is not sufficiently studied. The objective of our study was to explore the effects of food restriction prior to and during pregnancy on body weight and longevity of the second generation offspring. Adult female Wistar rats ("F0" generation) were 50% food restricted for one month prior to pregnancy (pre-pregnancy) or during pre-pregnancy and pregnancy. The third group was fed normally (control). The first generation offspring were normally fed until the 6(th) month of age to produce the second generation offspring; namely, the first-generation female rats were mated with male breeders from outside the experiment. The second generation offspring thus obtained were observed until natural death (up to 36 months). Compared to the controls, the second-generation male offspring whose "grandmothers (F0 females)" undernourished only during pre-pregnancy were significantly heavier from the 8(th) month of age, whereas no significant weight difference was found in the male offspring whose "grandmothers" were food-restricted during pre-pregnancy and pregnancy. Shorter lifespan was observed in the second-generation male offspring of "grandmothers" that were food-restricted either during pre-pregnancy or during pre-pregnancy and pregnancy. By contrast, no differences in body weight and lifespan were observed in all second-generation female offspring. In conclusion, maternal caloric restriction prior to pregnancy increases the body weight and shortens the longevity of the second-generation male offspring, indicating the sex-dependent transgenerational effect of maternal caloric restriction.

  10. Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats.

    PubMed

    Kawaguchi, Maiko; Morohoshi, Kaori; Imai, Hideki; Morita, Masatoshi; Kato, Nobumasa; Himi, Toshiyuki

    2010-01-01

    Isobutyl-paraben (IBP), a widely used preservative, exhibits estrogenic activity. We analyzed the effects of exposure to IBP during gestation and lactation via dam on social recognition behavior in ovariectomized offspring of Sprague-Dawley rats. Offspring were ovariectomized at 7 weeks of age, and were used in a social recognition test at 16 weeks of age. Each offspring was exposed to a novel ovariectomized rat four times and to a second novel rat in a fifth exposure. We counted the investigations by offspring of intruder rats. The IBP-exposed rats showed impaired social behavior compared with controls. These data imply that early exposure to IBP may have an effect on adult social behavior, which is reported to be an autism spectrum disorders in humans.

  11. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    PubMed

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring.

  12. Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague-Dawley rat offspring.

    PubMed

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

    2013-01-01

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

  13. Pre-Weaning Growth Hormone Treatment Reverses Hypertension and Endothelial Dysfunction in Adult Male Offspring of Mothers Undernourished during Pregnancy

    PubMed Central

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

    2013-01-01

    Maternal undernutrition results in elevated blood pressure (BP) and endothelial dysfunction in adult offspring. However, few studies have investigated interventions during early life to ameliorate the programming of hypertension and vascular disorders. We have utilised a model of maternal undernutrition to examine the effects of pre-weaning growth hormone (GH) treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (day 21), CON and UN pups received either saline (CON-S, UN-S) or GH (2.5 ug/g/day)(CON-GH, UN-GH). All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic blood pressure (SBP) was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependent vasodilators were investigated to determine vascular function. SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2 mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2). Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine (ACh). Furthermore, UN-S offspring vessels displayed a reduced vasodilator response in the presence of L-NG-Nitroarginine Methyl Ester (L-NAME), carbenoxolone (CBX), L-NAME and CBX, Tram-34 and Apamin. UN-GH vessels showed little difference in responses when compared to CON and significantly increased vasodilator responses when compared to UN-S offspring. Pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These data suggest that developmental cardiovascular programming is potentially

  14. GESTATIONAL EXPOSURE TO NONYLPHENOL CAUSES PRECOCIOUS MAMMARY GLAND DEVELOPMENT IN FEMALE RAT OFFSPRING

    EPA Science Inventory

    This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on ge...

  15. Chronic unpredictable stress before pregnancy reduce the expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor in hippocampus of offspring rats associated with impairment of memory.

    PubMed

    Huang, Yuejun; Shi, Xuechuan; Xu, Hongwu; Yang, Hanhua; Chen, Tian; Chen, Sihong; Chen, Xiaodong

    2010-07-01

    To investigate the effect of stress before pregnancy on memory function and serum corticosterone (COR) levels, as well as the expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) 2A (NR2A) and 2B (NR2B) receptors in the hippocampus of the offspring rats when they were 2 months postnatally. Adult female Sprague-Dawley (SD) rats were divided randomly into two groups: control group (n = 8) and chronic unpredictable stress (CUS) group (n = 12). All rats were tested in the open field test and sucrose intake test before and after CUS. The memory function of their offspring were tested in the Morris water maze. Serum COR levels were determined by using a standard radioimmunoassay kit. The expression of BDNF, NR2A and NR2B in the hippocampus of the offspring rats were studied by immunoreactivity quantitative analysis and real-time RT-PCR. (1) Following CUS, reduced open field test activity and decreased sucrose consumption were observed relative to controls. (2) The Morris water maze task demonstrated increased escape latency in the offspring rats of CUS group relative to controls (P < 0.01). No-platform probe testing showed reduced crossings for offspring of CUS relative to controls (P < 0.05). (3) CUS induced a significant increase in serum COR levels of the offspring rats (P < 0.01), but no difference was observed in the body or brain weight between the offspring of the two groups. (4) Immunoreactivity quantitative analysis shows that BDNF and NR2B in the offspring of CUS group was decreased in the CA3 and DG regions of the hippocampus compared to the control group offspring, but NR2A levels were not altered between the offspring of the two groups. (5) Real-time RT-PCR demonstrated that BDNF and NR2B mRNAs were significantly decreased in the offspring of the CUS group compared with the control group (P < 0.01). No significant difference in the levels of NR2A mRNA was detected between offspring of CUS and offspring of control groups. In our

  16. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    PubMed

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis.

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

    EPA Science Inventory

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

  18. Maternal immune activation affects litter success, size and neuroendocrine responses related to behavior in adult offspring.

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2013-07-02

    It is increasingly evident that influences other than genetics can contribute to offspring phenotype. In particular, maternal influences are an important contributing factor to offspring survival, development, physiology and behavior. Common environmental pathogens such as viral or bacterial microorganisms can induce maternal immune responses, which have the potential to alter the prenatal environment via multiple independent pathways. The effects of maternal immune activation on endocrine responses and behavior are less well studied and provide the basis for the current study. Our approach in the current study was two-pronged: 1) quantify sickness responses during pregnancy in adult female hamsters experiencing varying severity of immune responsiveness (i.e., differing doses of lipopolysaccharide [LPS]), and 2) assess the effects of maternal immune activation on offspring development, immunocompetence, hormone profiles, and social behavior during adulthood. Pregnancy success decreased with increasing doses of LPS, and litter size was reduced in LPS dams that managed to successfully reproduce. Unexpectedly, pregnant females treated with LPS showed a hypothermic response in addition to the more typical anorexic and body mass changes associated with sickness. Significant endocrine changes related to behavior were observed in the offspring of LPS-treated dams; these effects were apparent in adulthood. Specifically, offspring from LPS treated dams showed significantly greater cortisol responses to stressful resident-intruder encounters compared with offspring from control dams. Post-behavior cortisol was elevated in male LPS offspring relative to the offspring of control dams, and was positively correlated with the frequency of bites during agonistic interactions, and cortisol levels in both sexes were related to defensive behaviors, suggesting that changes in hypothalamo-pituitary-adrenal axis responsiveness may play a regulatory role in the observed behavioral

  19. Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.

    PubMed

    Sun, Bo; Liang, Nu-Chu; Ewald, Erin R; Purcell, Ryan H; Boersma, Gretha J; Yan, Jianqun; Moran, Timothy H; Tamashiro, Kellie L K

    2013-11-01

    Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

  20. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    SciTech Connect

    Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

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

    PubMed

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

    2014-02-01

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

  2. Exposure of pregnant rats to uranium and restraint stress: effects on postnatal development and behavior of the offspring.

    PubMed

    Sánchez, Domènec J; Bellés, Montserrat; Albina, Maria L; Gómez, Mercedes; Linares, Victoria; Domingo, José L

    2006-12-07

    The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited.

  3. Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring.

    PubMed

    Sasaki, Aya; Constantinof, Andrea; Pan, Pauline; Kupferschmidt, Dave A; McGowan, Patrick O; Erb, Suzanne

    2014-05-15

    There is evidence that maternal experience prior to pregnancy can play an important role in behavioral, physiological, and genetic programming of offspring. Likewise, exposure to cocaine in utero can result in marked changes in central nervous system function of offspring. In this study, we examined whether exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of behavior, physiology, and gene expression in offspring. Multiple outcome measures were examined in adult male offspring: (1) behavioral expression of cocaine-induced psychomotor activation; (2) levels of corticosterone in response to immobilization stress; and (3) expression of multiple genes, including dopamine receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin-releasing factor (CRF), in functionally relevant brain regions. Adult Sprague-Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days, and were then mated to drug naïve males of the same strain. Separate groups of adult male offspring were tested for their acute psychomotor response to cocaine (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization stress, and expression of multiple genes using quantitative PCR. Offspring of dams exposed to cocaine prior to conception exhibited increased psychomotor sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene expression of GR or CRF genes were altered. These data suggest that cocaine exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine in offspring, possibly via alterations in dopamine function that include upregulation of the DRD1.

  4. Dietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish

    PubMed Central

    Jhinku, Noel; Meier, Michael; Horsfield, Julia

    2016-01-01

    The burden of malnutrition, including both over- and undernutrition, is a major public health concern. Here we used a zebrafish model of diet-induced obesity to analyze the impact of dietary intake on fertility and the phenotype of the next generation. Over an eight-week period, one group received 60 mg of food each day (60 mg arm), while another received 5 mg (5 mg arm). At the end of the diet, the body mass index of the 60 mg arm was 1.5 fold greater than the 5 mg arm. The intervention also had a marked impact on fertility; breeding success and egg production in the 60 mg arm were increased 2.1- and 6.2-fold compared to the 5 mg arm, respectively. Transcriptome analysis of eggs revealed that transcripts involved in metabolic biological processes differed according to dietary intake. The progeny from the differentially fed fish were more likely to survive when the parents had access to more food. An intergenerational crossover study revealed that while parental diet did not influence weight gain in the offspring, the progeny of well-fed parents had increased levels of physical activity when exposed again to high nutrient availability. We conclude that dietary intake has an important influence on fertility and the subsequent fitness of offspring, even prior to breeding. PMID:27870856

  5. Effects of paternal obesity on growth and adiposity of male rat offspring.

    PubMed

    Lecomte, Virginie; Maloney, Christopher A; Wang, Kristy W; Morris, Margaret J

    2017-02-01

    Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk.

  6. Impact of cafeteria feeding during lactation in the rat on novel object discrimination in the offspring.

    PubMed

    Wright, Thomas M; King, Madeleine V; Davey, William G; Langley-Evans, Simon C; Voigt, Jörg-Peter W

    2014-12-28

    There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.

  7. Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring.

    PubMed

    You, Young-Ah; Lee, Ji Hye; Kwon, Eun Jin; Yoo, Jae Young; Kwon, Woo-Sung; Pang, Myung-Geol; Kim, Young Ju

    2015-11-01

    Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p < 0.05). Moreover, the expression levels of betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial were negatively correlated with serum homocysteine concentration in male offspring exposed to maternal food restriction during gestation and normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender

  8. Maternal corticosterone is transferred to avian yolk and may alter offspring growth and adult phenotype.

    PubMed

    Hayward, Lisa S; Wingfield, John C

    2004-02-01

    Many environmental perturbations may elevate plasma corticosterone in laying birds, including disease, poor body condition, high predator density, anthropogenic disturbance, and/or food scarcity. When adverse conditions are not dire enough to dictate foregoing reproduction, maternal corticosterone in egg yolk may phenotypically engineer offspring so as to maximize success under the constraints of the local environment. We tested the hypotheses that corticosterone in avian egg yolk should correlate with corticosterone in maternal circulation at the time of laying, and that high corticosterone in yolk should then influence offspring development and adult phenotype. We implanted female Japanese quail (Coturnix coturnix japonica) with corticosterone-filled or empty implants and measured concentrations of corticosterone in the yolk of their eggs. Then we incubated the eggs and raised the chicks to test for effects on growth and hypothalamo-pituitary-adrenal response to capture and restraint in adult offspring. We found that corticosterone implants significantly increased corticosterone in yolk. Furthermore, chicks of corticosterone-implanted mothers grew more slowly than controls and showed higher activity of the hypothalamo-adrenal axis in response to capture and restraint as adults. These results suggest that stress experienced by a laying bird has significant effects on offspring development and adult phenotype, possibly mediated by the transfer of maternal corticosterone to yolk.

  9. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    PubMed

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring.

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

    PubMed

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

    2014-08-01

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

  11. Prenatal and lactation nicotine exposure affects morphology and function of brown adipose tissue in male rat offspring.

    PubMed

    Fan, Jie; Ping, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Liu, Han-Xiao; Zhang, Jing; Yan, You-E

    2016-01-01

    The aim of this study was to investigate the effects of prenatal and lactation nicotine exposure on the morphology and function of brown adipose tissue (BAT) in male rat offspring. We conducted a morphological assay and gene expression study of interscapular BAT (iBAT) in male rat offspring. The male offspring from nicotine-exposed dams exhibited higher body weight and iBAT weight. Hematoxylin and eosin staining and transmission electron microscopy showed that iBAT from nicotine-exposed male offspring presented a "whitening" phenotype characterized by lipid droplet accumulation and impaired mitochondria with a randomly oriented and fractured cristae. The expression of the iBAT structure and function-related genes all decreased in nicotine-exposed male offspring. These data indicate that prenatal and lactation nicotine exposure affects morphology and function of iBAT in male rat offspring.

  12. Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring.

    PubMed

    Pallarés, M E; Adrover, E; Imsen, M; González, D; Fabre, B; Mesch, V; Baier, C J; Antonelli, M C

    2014-10-10

    We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain

  13. Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

    PubMed Central

    Sun, Yanhong; Ouyang, Juan; Xie, Renfeng; Wang, Xueping

    2016-01-01

    Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process. Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs). Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%, P < 0.05) and AIA (63.6% versus 0%, P < 0.05) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region. Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity. PMID:28078304

  14. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  15. Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

    PubMed

    Braddock, Rattana; Simán, C Martin; Hamilton, Katherine; Garland, Hugh O; Sibley, Colin P

    2002-05-01

    Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.

  16. Behavioral and neurochemical alterations in the offspring of rats after maternal or paternal inhalation exposure to the industrial solvent 2-methoxyethanol.

    PubMed

    Nelson, B K; Brightwell, W S; Burg, J R; Massari, V J

    1984-02-01

    The industrial solvent 2-methoxyethanol (2ME) has antifertility effects in male rats at 300 ppm and is teratogenic in rats and rabbits at 50 ppm. The present research investigated if exposure of paternal or maternal animals to 25 ppm 2ME, the current U.S. permissible occupational exposure limit, would produce detectable effects in the offspring. Eighteen male young-adult Sprague-Dawley rats were exposed to 25 ppm 2ME 7 hr/day, 7 days/week for 6 weeks; they were then mated with untreated females which were allowed to deliver and rear their young. In addition, groups of 15 pregnant rats were exposed 7 hr/day on gestation days 7-13 or 14-20 and allowed to deliver and rear their young. At birth, litters were culled to 4 females and 4 males for behavioral testing of neuromotor function, activity, and simple learning ability on days 10 through 90. In addition, brains from newborn and 21-day-old offspring were analyzed for neurochemical deviations from controls. No effects on paternal or maternal animals, nor on the number or weight of live offspring, were noted. Behavioral testing revealed significant differences from controls only in avoidance conditioning of offspring of mothers exposed on days 7-13. In contrast, neurochemical deviations were observed in brains from 21-day-old offspring from the paternally exposed group as well as from both maternally exposed groups; changes were numerous in the brainstem and cerebrum but were fewer in the cerebellum and midbrain. Thus it appears that both paternal and maternal inhalation of 25 ppm 2ME produces some effect which is reflected in neurochemical deviations in the offspring.

  17. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    SciTech Connect

    Martinez–Arguelles, D.B.; McIntosh, M.; Rohlicek, C.V.; Culty, M.; Zirkin, B.R.; Papadopoulos, V.

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

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

    PubMed

    Rabaglino, María Belén; Moreira-Espinoza, María José; Lopez, Juan Pablo; Garcia, Nestor Horacio; Beltramo, Dante

    2016-11-30

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

  19. Chronic exposure of gestation rat to sevoflurane impairs offspring brain development.

    PubMed

    Wang, Yuheng; Cheng, Yongxia; Liu, Guibo; Tian, Xiaodan; Tu, Xuefeng; Wang, Junke

    2012-06-01

    Recently it was demonstrated that the exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors can trigger widespread apoptotic neurodegeneration. Sevoflurane is a new inhalation anesthetic agent commonly used in the clinic. Here we address whether sevoflurane could induce neurotoxicity in the developing brain. Sevoflurane was administered to rats before pregnancy and pregnant rats on embryonic days E6, E10, E14, and E18 1MAC for 6 h, and we employed histopathological, immunochemistry, semiquantitative RT-PCR, and Western blot to investigate the effect of the exposure of pregestation and gestation rats to sevoflurane on the offspring brain development. The results showed that the exposure of gestation but not pregestation rats to sevoflurane-induced extensive apoptotic neurodegeneration in the hippocampus of offspring at P0, P7, and P14, accompanied by altered expression of casepase-3, GAP-43, nNOS, NMDAR1, NMDAR2A, and NMDAR2B. Furthermore, upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein levels were observed in the hippocampus of offspring at P0, P7, and P14 from rats exposed to sevoflurane at gestation, but not pregestation. In summary, our data suggest that sevoflurane induces developmental neurotoxicity in rats and this may be attributed to the upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein in the hippocampus.

  20. Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats

    PubMed Central

    Zambrano, E; Martínez-Samayoa, P M; Rodríguez-González, G L; Nathanielsz, P W

    2010-01-01

    Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected. PMID:20351043

  1. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats.

    PubMed

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-Kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3-20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light-dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light-dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.

  2. Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

    NASA Technical Reports Server (NTRS)

    Alberts, J. R.; Burden, H. W.; Hawes, N.; Ronca, A. E.

    1996-01-01

    To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

  3. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    PubMed

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-08

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

  6. Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.

    PubMed

    Eriksson, U J; Simán, C M

    1996-11-01

    The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant diabetic and normal rats were fed either a standard diet or a diet enriched with 1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs. 3.68 g) when the mothers were fed a standard diet. The BHT diet increased the fetal weight in the offspring of diabetic rats (3.17 g), with no change in fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier than the placentas of normal rats; this difference was not present in the BHT-fed rats. The BHT treatment had no effect on the rate of resorptions, which was increased in the diabetic rats compared with the normal rats. In contrast, the increased rate of congenital malformations in the offspring of diabetic rats (19%), compared with that in the normal rats (0%), was markedly decreased by the BHT diet (2.3%). No malformations were found in the normal rats treated with BHT. These data support the notion that an excess of free oxygen radicals in the embryo contributes to the teratogenic process of diabetic pregnancy and, thus, suggest an area for future preventive therapeutic treatment.

  7. Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring?

    PubMed

    Khandaker, G M; Dibben, C R M; Jones, P B

    2012-06-01

    Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association.

  8. Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring?

    PubMed Central

    Khandaker, G M; Dibben, C R M; Jones, P B

    2012-01-01

    Summary Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association. PMID:22188548

  9. Parental Involvement in Residential Care and Perceptions of their Offspring's Life Satisfaction in Residential Facilities for Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Schwartz, Chaya

    2005-01-01

    Background: This study examined parental involvement in relocation and post-placement care of offspring in residential facilities for adults with intellectual disability, as well as the characteristics of residents, parents, and residential institutions and the effect of those variables on parental perceptions of their offspring's life…

  10. Effect of chronic exposure to methylxanthines on diazepam cerebral binding in female rats and their offsprings.

    PubMed

    Daval, J L; Vert, P

    1986-06-01

    Caffeine, theophylline or saline were injected daily into female rats during the gestation and lactation periods. Crude synaptosomal membranes were isolated from the brains of offsprings at various stages of development and their ability to specifically bind [3H]diazepam was tested. An other approach consisted of injecting [3H]diazepam into offsprings and cerebral specifically bound diazepam was measured. It was shown that methylxanthines were able to inhibit [3H]diazepam binding by reducing total number of binding sites in the brain of 5- and 15-day-old rats born from treated mothers, with a total recovery of control values at 25 days of age. Moreover, in vivo percentage of cerebral bound diazepam dramatically fell when rats were exposed to methylxanthines in utero and through the mother's milk. Since caffeine and theophylline displace diazepam binding not necessarily in a competitive manner, it is suggested that they could interfere with diazepam as adenosine antagonists.

  11. Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy.

    PubMed

    Howland, J G; Cazakoff, B N; Zhang, Y

    2012-01-10

    Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long-Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal

  12. Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

    PubMed Central

    Youngson, Neil A; Lecomte, Virginie; Maloney, Christopher A; Leung, Preston; Liu, Jia; Hesson, Luke B; Luciani, Fabio; Krause, Lutz; Morris, Margaret J

    2016-01-01

    There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16–19 weeks old, n = 14/14). A small (0.25%) increase in total 5-methyl-2’-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq) and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers) revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells. PMID:26608942

  13. Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring.

    PubMed

    Youngson, Neil A; Lecomte, Virginie; Maloney, Christopher A; Leung, Preston; Liu, Jia; Hesson, Luke B; Luciani, Fabio; Krause, Lutz; Morris, Margaret J

    2016-01-01

    There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14). A small (0.25%) increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq) and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers) revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

  14. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    PubMed

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

  15. Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring.

    PubMed

    Allina, Jorge; Grabowski, Jacquelin; Doherty-Lyons, Shannon; Fiel, M Isabel; Jackson, Christine E; Zelikoff, Judith T; Odin, Joseph A

    2011-01-01

    Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring.

  16. Development and learning in the offspring of rats fed an alcohol diet on a short- or long-term basis.

    PubMed

    Cohen, L E; Cogan, D C; Jones, J R; Cogan, C C

    1985-01-01

    The offspring of rats fed a diet containing 12.5% (v/v) ethanol prior to, and during, gestation (LTE) were compared to the offspring of rats fed the same diet during gestation only (STE) in three studies. In Study I the neonates were tested on a variety of neuroreflex tasks, in Study II the offspring were tested in an activity wheel and open field, and in Study III the offspring were trained in a runway under partial or consistent reward conditions. Results indicated that STE offspring were delayed in developing fur and in opening their eyes, they righted more rapidly, and were slower in developing a reaction to and habituating to an auditory stimulus than their controls (STC) and the LTE offspring. Generally, movement was greater for ethanol exposed offspring and the LTE offspring showed more persistent fear-related responses than the STE offspring. No statistically reliable differences in learning or extinction were found among the groups, although a trend towards better learning and less resistance to extinction was noted in the LTE animals. Long-term alcohol use seems to attenuate the effects of gestational alcohol in rats.

  17. Prenatal stress changes the glycoprotein GPM6A gene expression and induces epigenetic changes in rat offspring brain.

    PubMed

    Monteleone, Melisa C; Adrover, Ezequiela; Pallarés, María Eugenia; Antonelli, Marta C; Frasch, Alberto C; Brocco, Marcela A

    2014-01-01

    Prenatal stress (PS) exerts strong impact on fetal brain development and on adult offspring brain functions. Previous work demonstrated that chronic stress alters the mRNA expression of GPM6A, a neuronal glycoprotein involved in filopodium extension. In this work, we analyzed the effect of PS on gpm6a expression and the epigenetic mechanisms involved. Pregnant Wistar rats received restraint stress during the last week of gestation. Male offspring were sacrificed on postnatal days 28 and 60. Hippocampus and prefrontal cortex samples were analyzed for gene expression (qPCR for mRNAs and microRNAs), methylation status (bisulfite conversion) and protein levels. Hippocampal neurons in culture were used to analyze microRNA overexpression effects. Prenatal stress induced changes in gpm6a levels in both tissues and at both ages analyzed, indicating a persistent effect. Two CpG islands in the gpm6a gene were identified. Variations in the methylation pattern at three specific CpGs were found in hippocampus, but not in PFC samples from PS offspring. microRNAs predicted to target gpm6a were identified in silico. qPCR measurements showed that PS modified the expression of several microRNAs in both tissues, being microRNA-133b the most significantly altered. Further studies overexpressing this microRNA in neuronal cultures showed a reduction in gmp6a mRNA and protein level. Moreover filopodium density was also reduced, suggesting that GPM6A function was affected. Gestational stress affected gpm6a gene expression in offspring likely through changes in methylation status and in posttranscriptional regulation by microRNAs. Thus, our findings propose gpm6a as a novel target for epigenetic regulation during prenatal stress.

  18. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

    PubMed

    García, Ana Paula; Palou, Mariona; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

    2011-02-18

    Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+) and NPY(+), suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+) and NPY(+). Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture.

  19. Effect of prenatal or perinatal nicotine exposure on neonatal thyroid status and offspring growth in rats.

    PubMed

    Chen, Wei-Jung A; Kelly, Ryan B

    2005-01-28

    Smoking during pregnancy causes intrauterine growth retardation and low birth weight of the offspring. However, it is unclear whether nicotine, rather than other compounds from a cigarette, would mediate long-term growth retardation. There is a body of evidence suggesting that optimal thyroid status is important for the normal development of the fetus. Therefore, these studies examined whether developmental nicotine exposure would interfere with the growth of the offspring and alter the thyroid status of neonates. Pregnant Sprague-Dawley rats were given 0, 15 or 25 mg nicotine pellets throughout pregnancy. Some offspring continued to receive 1 or 2 mg/kg/day nicotine during early postnatal period. The remaining offspring received no further treatment after birth. The body weight of all offspring was monitored until adulthood. Additionally, the neonatal thyroid status from all treatment groups was assessed from the serum of 10-day-old pups. Regardless of the timing of nicotine exposure, the nicotine treatment significantly increased the body weight in female offspring starting on postnatal day (PD) 35 and such an increase persisted into adulthood (PD 91). However, this nicotine exposure paradigm led to a transient increase in male offspring body weight on PD 35. Furthermore, current nicotine exposure regimens did not alter the total T4 level, T3 uptake and the calculated Free T4 index. The present findings are in agreement with some clinical studies reporting a higher body weight among children born to mothers who smoked during pregnancy. Furthermore, the data on thyroid status suggest that cigarette smoking-induced alterations in thyroid status might be mediated through compounds in cigarettes other than nicotine.

  20. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    USGS Publications Warehouse

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  1. Gestational Hypothyroidism Increases the Severity of Experimental Autoimmune Encephalomyelitis in Adult Offspring

    PubMed Central

    Albornoz, Eduardo A.; Carreño, Leandro J.; Cortes, Claudia M.; Gonzalez, Pablo A.; Cisternas, Pablo A.; Cautivo, Kelly M.; Catalán, Tamara P.; Opazo, M. Cecilia; Eugenin, Eliseo A.; Berman, Joan W.; Bueno, Susan M.; Kalergis, Alexis M.

    2013-01-01

    Background: Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. Methods: Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. Results: We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4+ and CD8+ infiltration, and increased oligodendrocyte death. Conclusions: These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring. PMID:23777566

  2. Offspring metabolomic response to maternal protein restriction in a rat model of intrauterine growth restriction (IUGR).

    PubMed

    Alexandre-Gouabau, Marie-Cécile; Courant, Frédérique; Le Gall, Gwénaëlle; Moyon, Thomas; Darmaun, Dominique; Parnet, Patricia; Coupé, Bérengère; Antignac, Jean-Philippe

    2011-07-01

    Intrauterine growth restriction (IUGR), along with postnatal growth trajectory, is closely linked with metabolic diseases and obesity at adulthood. The present study reports the time-dependent metabolomic response of male offspring of rat dams exposed to maternal adequate protein diet during pregnancy and lactation (CC) or protein deprivation during pregnancy only (IUGR with rapid catch-up growth, RC) or through pregnancy and lactation (IUGR with slow postnatal growth, RR). Plasma LC-HRMS metabolomic fingerprints for 8 male rats per group, combined with multivariate statistical analysis (PLS-DA and HCA), were used to study the impact of IUGR and postnatal growth velocity on the offspring metabolism in early life (until weaning) and once they reached adulthood (8 months). Compared with CC rats, RR pups had clear-cut alterations in plasma metabolome during suckling, but none at adulthood; in contrast, in RC pups, alterations in metabolome were minimal in early life but more pronounced in the long run. In particular, our results pinpoint transient alterations in proline, arginine, and histidine in RR rats, compared to CC rats, and persistent differences in tyrosine and carnitine, compared to RC rats at adulthood. These findings suggest that the long-term deregulation in feeding behavior and fatty acid metabolism in IUGR rats depends on postnatal growth velocity.

  3. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  4. Effects of Afobazole on Postnatal Development of Rat Offspring.

    PubMed

    Bugaeva, L I; Denisova, T D; Sergeeva, S A; Morozova, Yu A; Kharlamov, I V

    2017-02-01

    Physical development, development of sensory and motor reflexes, behavioral and mnestic patterns were studied infantile and juvenile rat pups born by female rats receiving Afobazole during pregnancy. Physical development and development of sensory and motor reflexes in rats were completed without pathologies by the age of 2 months. During the infantile period, the rat pups demonstrated reduced body weight gain, delayed eye opening and pupillary response formation, decreased muscle force, and suppressed motor behavior. During the juvenile period, body weight gain and development of motor behavior were intensified. Females demonstrated later vagina opening and poorer mnestic responses. In males, the terms of sexual maturation were unchanged and processes of learning and memory retrieval were not impaired.

  5. Peri, pre and postnatal morphine exposure: exposure-induced effects and sex differences in the behavioural consequences in rat offspring.

    PubMed

    Timár, Julia; Sobor, Melinda; Király, Kornél P; Gyarmati, Susanna; Riba, Pál; Al-Khrasani, Mahmoud; Fürst, Susanna

    2010-02-01

    This study investigated the behavioural consequences of peri, pre and postnatal morphine (MO) exposure in rats. From gestational day 1 dams were treated with either saline or MO subcutaneously once a day (5 mg/kg on the first 2 days, 10 mg/kg subsequently). Spontaneous locomotor activity in a new environment (habituation) and antinociceptive effects of MO were measured separately in male and female pups after weaning and also in late adolescence or adulthood. The rewarding effect of MO was assessed by conditioned place preference in adult animals. Both exposure-induced and sex differences were observed. A significant delay in habituation to a new environment and decreased sensitivity to the antinociceptive effect of MO were found in male offspring of MO-treated dams. In contrast, the place preference induced by MO was enhanced in the MO-exposed adult animals and this effect was more marked in females. Prenatal exposure to MO resulted in more marked changes than the postnatal exposure through maternal milk. The results indicate that a medium MO dose administered once-daily results in long-term consequences in offspring and may make them more vulnerable to MO abuse in adulthood.

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

    PubMed

    Starr-Phillips, Emily J; Beery, Annaliese K

    2014-07-01

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

  7. Maternal trans fat intake during pregnancy or lactation impairs memory and alters BDNF and TrkB levels in the hippocampus of adult offspring exposed to chronic mild stress.

    PubMed

    Pase, Camila Simonetti; Roversi, Karine; Roversi, Katiane; Vey, Luciana Taschetto; Dias, Verônica Tironi; Veit, Juliana Cristiana; Maurer, Luana Haselein; Duarte, Thiago; Emanuelli, Tatiana; Duarte, Marta; Bürger, Marilise Escobar

    2017-02-01

    This study aimed to assess the influence of maternal dietary fat intake during pregnancy or lactation on memory of adult offspring after chronic mild stress (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the animals were exposed to CMS following behavioral assessments. While the adult offspring born under influence of SO/FO and HVF supplementations during pregnancy showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA metabolites, respectively, in the hippocampus, adult offspring born from supplemented dams during lactation showed higher levels of their precursors: ALA and LA. However, only HVF supplementation allowed TFA incorporation of adult offspring, and levels were higher in lactation period. Adult offspring born from dams supplemented with trans fat in both pregnancy and lactation showed short and long-term memory impairments before and after CMS. Furthermore, our study also showed higher memory impairment in offspring born from HVF-supplemented dams during lactation in comparison to pregnancy. BDNF expression was increased by stress exposure in offspring from both SO/FO- and HVF-supplemented dams during pregnancy. In addition, offspring from HVF-supplemented dams showed decreased TrkB expression in both supplemented periods, regardless of stress exposure. In conclusion, these findings show for the first time that the type of dietary FA as well as the period of brain development is able to change FA incorporation in brain neural membranes.

  8. Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring.

    PubMed

    Tufik, S; Fujita, K; Seabra, M de L; Lobo, L L

    1994-01-01

    Valeriana officinalis L. (Valerianaceae) is widely known to be associated with sedative properties. The effects of a valepotriates mixtures on mothers and progeny were evaluated in rats. A 30-day administration of valepotriates did not change the average length of estral cycle, nor the number of estrous phases during this period. Also, there were no changes on the fertility index. Fetotoxicity and external examination studies did not show differences, although internal examination revealed an increase in number of retarded ossification after the highest doses employed--12 and 24 mg/kg. No changes were detected in the development of the offspring after treatment during pregnancy. As for temperature, valepotriates caused a hypothermizant effect after administration by the intraperitoneal route but not after oral administration. Generally, the valepotriates employed induced some alterations after administration by the intraperitoneal route, but doses given orally were innocuous to pregnant rats and their offspring.

  9. Host suitability of a gregarious parasitoid on beetle hosts: flexibility between fitness of adult and offspring.

    PubMed

    Li, Li; Sun, Jianghua

    2011-04-19

    Behavioral tactics play a crucial role in the evolution of species and are likely to be found in host-parasitoid interactions where host quality may differ between host developmental stages. We investigated foraging decisions, parasitism and related fitness in a gregarious ectoparasitoid, Sclerodermus harmandi in relation to two distinct host developmental stages: larvae and pupae. Two colonies of parasitoids were reared on larvae of Monochamus alternatus and Saperda populnea (Cerambycidae: Lamiinae). Paired-choice and non-choice experiments were used to evaluate the preference and performance of S. harmandi on larvae and pupae of the two species. Foraging decisions and offspring fitness-related consequences of S. harmandi led to the selection of the most profitable host stage for parasitoid development. Adult females from the two colonies oviposited more quickly on pupae as compared to larvae of M. alternatus. Subsequently, their offspring development time was faster and they gained higher body weight on the pupal hosts. This study demonstrates optimal foraging of intraspecific détente that can occur during host-parasitoid interactions, of which the quality of the parasitism (highest fitness benefit and profitability) is related to the host developmental stage utilized. We conclude that S. harmandi is able to perfectly discriminate among host species or stages in a manner that maximizes its offspring fitness. The results indicated that foraging potential of adults may not be driven by its maternal effects, also induced flexibly with encountering prior host quality.

  10. Host Suitability of a Gregarious Parasitoid on Beetle Hosts: Flexibility between Fitness of Adult and Offspring

    PubMed Central

    Li, Li; Sun, Jianghua

    2011-01-01

    Behavioral tactics play a crucial role in the evolution of species and are likely to be found in host-parasitoid interactions where host quality may differ between host developmental stages. We investigated foraging decisions, parasitism and related fitness in a gregarious ectoparasitoid, Sclerodermus harmandi in relation to two distinct host developmental stages: larvae and pupae. Two colonies of parasitoids were reared on larvae of Monochamus alternatus and Saperda populnea (Cerambycidae: Lamiinae). Paired-choice and non-choice experiments were used to evaluate the preference and performance of S. harmandi on larvae and pupae of the two species. Foraging decisions and offspring fitness-related consequences of S. harmandi led to the selection of the most profitable host stage for parasitoid development. Adult females from the two colonies oviposited more quickly on pupae as compared to larvae of M. alternatus. Subsequently, their offspring development time was faster and they gained higher body weight on the pupal hosts. This study demonstrates optimal foraging of intraspecific détente that can occur during host-parasitoid interactions, of which the quality of the parasitism (highest fitness benefit and profitability) is related to the host developmental stage utilized. We conclude that S. harmandi is able to perfectly discriminate among host species or stages in a manner that maximizes its offspring fitness. The results indicated that foraging potential of adults may not be driven by its maternal effects, also induced flexibly with encountering prior host quality. PMID:21526176

  11. Effects on reproduction in female offspring from Sprague-Dawley rats fed 10% snakeweed (Gutierrezia microcephala) throughout pregnancy and concurrent treatment with safflower oil.

    PubMed

    Staley, E C; Smith, G S; Greenberg, J A

    1995-10-01

    Previous studies determined that safflower oil administration provided protection against the embryotoxicity seen following ingestion of 10% snakeweed (Gutierrezia microcephala) throughout pregnancy. Sixty-two young primiparous female rats born in those studies were paired with adult male Sprague-Dawley rats. After 4 d they were removed and carried their litters to term. Observations were made of the presence and extent of reproductive effects attributable to the 10% snakeweed exposure and differences in fecundity that were attributable to dosing with safflower oil or normal saline during the snakeweed exposure. Of the 62 rats, 50 carried litters to term and approximated the reproductive efficiency of normal primiparous Sprague-Dawley rats. There was no significant difference between the fecundity of females born to rats fed the 10% snakeweed and dosed with safflower oil, those born of rats fed snakeweed dosed with normal saline, or those fed a snakeweed-free diet and dosed with normal saline. Regardless of the diet or treatment administered, dams carrying their litters to parturition gave birth to healthy, normo-reproductive offspring. While the toxic principles in Gutierrezia species plants may act as estrogenic or anti-estrogenic compounds, they did not impair fertility in the female offspring of dosed rats.

  12. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  13. Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring

    PubMed Central

    Chen, Rui; Deng, Youcai; Liao, Xi; Wei, Yanling; Li, Xiaohui; Su, Min; Yu, Jianhua; Yi, Ping

    2017-01-01

    Prenatal exposure to inflammation results in hypertension during adulthood but the mechanisms are not well understood. Maternal exposure to lipopolysaccharide (LPS) alters interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the fetal environment. As reported in many recent studies, IL-6 regulates DNA methyltransferases (DNMTs) through the transcription factor friend leukemia virus integration 1 (Fli-1). The present study explores the role of intrarenal DNMTs during development of hypertension induced by prenatal exposure to LPS. Pregnant rats were randomly divided into four treatment groups: control, LPS, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), and the combination of LPS and PDTC. Expression of IL-6, Fli-1, TNF-α, DNMT1 and DNMT3B was significantly increased in the offspring of LPS-treated rats. Global DNA methylation level of renal cortex also increased dramatically in rat offspring of the LPS group. Prenatal PDTC administration reversed the increases in gene expression and global DNA methylation level. These findings suggest that prenatal exposure to LPS may result in changes of intrarenal DNMTs through the IL-6/Fli-1 pathway and TNF-α, which probably involves hypertension in offspring due to maternal exposure to inflammation. PMID:28103274

  14. Inflammatory milieu as an early marker of kidney injury in offspring rats from diabetic mothers.

    PubMed

    Correa-Costa, Matheus; Landgraf, Maristella A; Cavanal, Maria F; Semedo, Patricia; Vieira, Daniel A G; De Marco, Davi T K; Hirata, Aparecida E; Câmara, Niels O S; Gil, Frida Z

    2012-08-15

    The present study investigated the early presence of inflammatory response in renal tissue of young offspring from diabetic mothers. The effect of L-arginine (L-arg) supplementation was also investigated. The offspring was divided into four groups: group CO (controls); group DO (diabetic offspring); group CA (CO receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution). Glycemia, arterial pressure and renal function were evaluated; gene and protein expression of pro-inflammatory cytokines were also measured. Blood pressure levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg administration caused a significant decrease in the DA group, at both ages. DO rats showed a significantly blunted glycemic response to exogenous insulin. In 2 month-old DO animals, renal protein expression of pro-inflammatory molecules was significantly increased. At six months of age, we also observed an increase in gene expression of pro-inflammatory molecules, whereas L-arg supplementation prevented this increase at both ages. Our data suggest that activation of inflammatory pathways is present early in the kidney of DO rats, and that L-arg can attenuate the expression of these markers of tissue inflammation. Our results also reinforce the concept that intrauterine environmental factors are a fundamental determinant in the development of metabolic and vascular diseases later in life.

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

    PubMed

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

    2016-04-01

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

  16. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-10-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut.

  17. Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring.

    PubMed

    Sharma, Sona S; Jangale, Nivedita M; Harsulkar, Abhay M; Gokhale, Medha K; Joshi, Bimba N

    2017-02-08

    Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation. Offspring were fed on control diet post-weaning and studied till 30 weeks. Lipid profile, serum glutamate pyruvate transaminase (SGPT), calcium and vitamin D levels were analyzed. Liver fat deposition, omega-3 fatty acids level and mRNA expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), interleukin 6 (IL-6), superoxide dismutase 1 (SOD-1) and uncoupling protein 2 (UCP2) were determined. Low serum vitamin D levels with an increase in SGPT and TG levels in CaD and VDD female offspring were observed. Severe liver steatosis with down-regulation of PPAR-α and UCP2 and up-regulation of SREBP-1c, IL-6 and SOD-1 was observed in the female offspring born to deficient dams. CaD and VDD male offspring showed mild steatosis and down-regulation of UCP2 and SOD-1. We conclude that maternal calcium and vitamin D deficiency programs abnormal lipid metabolism and hepatic gene expression in the F1 generation female offspring leading to hepatic steatosis, despite feeding them on control diet post-weaning.

  18. Large litter rearing improves leptin sensitivity and hypothalamic appetite markers in offspring of rat dams fed high-fat diet during pregnancy and lactation.

    PubMed

    Sun, Bo; Song, Lin; Tamashiro, Kellie L K; Moran, Timothy H; Yan, Jianqun

    2014-09-01

    Maternal high-fat (HF) diet has long-term consequences on the offspring's metabolic phenotype. Here, we determined the effects of large litter (LL) rearing in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on standard chow (CHOW) or HF diet throughout gestation and lactation. Pups were raised in normal litters (NLs) (10 pups/dam) or LLs (16 pups/dam) during lactation, resulting in 4 groups: CHOW-NL, CHOW-LL, HF-NL, and HF-LL. The offspring were weaned onto to either CHOW or HF diet on postnatal day 21. Male and female pups with maternal HF diet (HF-NL) had greater body weight and adiposity, higher plasma leptin levels, impaired glucose tolerance, abnormal hypothalamic leptin signaling pathways (lower leptin receptor-b [OB-Rb] and signal transducer and activator of transcription 3, higher suppressor of cytokine signaling 3 mRNA expression) and appetite markers (lower neuropeptide Y and Agouti-related peptide mRNA expression), and reduced phospho-signal transducer and activator of transcription 3 level in response to leptin in the arcuate nucleus at weaning, whereas LL rearing normalized these differences. When weaned onto CHOW diet, adult male offspring from HF diet-fed dams continued to have greater adiposity, higher leptin levels, and lower hypothalamic OB-Rb, and LL rearing improved them. When weaned onto HF diet, both adult male and female offspring with maternal HF diet had greater body weight and adiposity, higher leptin levels, impaired glucose tolerance, lower OB-Rb, and higher suppressor of cytokine signaling 3 in hypothalamus compared with those of CHOW dams, whereas LL rearing improved most of them except male OB-Rb expression. Our data suggest that LL rearing improves hypothalamic leptin signaling pathways and appetite markers in an age- and sex-specific manner in this model.

  19. Effect of caffeine on rat offspring from treated dams.

    PubMed

    Aeschbacher, H U; Milon, H; Poot, A; Würzner, H P

    1980-11-01

    Pregnant Sprague-Dawley rats were given caffeine at 1.0, 0.5 and 0.25 g/kg diet during gestation and lactation. At birth, half of the pups from control and treated rats at each dose level were exchanged and cross fostered. Two litters were produced by each animal from each of the experimental groups. Caffeine at dietary concentrations of 0.5 and 0.25 g/kg throughout gestation and lactation had no significant effect on birth weight, litter size or development. There was also no effect at these doses following treatment during either gestation alone, or lactation alone. At 1.0 g/kg there was a slight reduction of birth weight, as well as a trend towards lower weight gain in litters from dams fed the test diet throughout gestation and lactation.

  20. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters.

    PubMed

    Foster, Paul M D

    2006-02-01

    Certain Phthalate esters have been shown to produce reproductive toxicity in male rodents with an age dependent sensitivity in effects with foetal animals being more sensitive than neonates which are in turn more sensitive than pubertal and adult animals. While the testicular effects of phthalates in rats have been known for more than 30 years, recent attention has been focused on the ability of these agents to produce effects on reproductive development in male offspring after in utero exposure. These esters and in particular di-butyl, di-(2-ethylhexyl) and butyl benzyl phthalates have been shown to produce a syndrome of reproductive abnormalities characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism and testicular injury together with permanent changes (feminization) in the retention of nipples/areolae (sexually dimorphic structures in rodents) and demasculinization of the growth of the perineum resulting in a reduced anogenital distance (AGD). Critical to the induction of these effects is a marked reduction in foetal testicular testosterone production at the critical window for the development of the reproductive tract normally under androgen control. A second Leydig cell product, insl3, is also significantly down regulated and is likely responsible for the cryptorchidism commonly seen in these phthalate-treated animals. The testosterone decrease is mediated by changes in gene expression of a number of enzymes and transport proteins involved in normal testosterone biosynthesis and transport in the foetal Leydig cell. Alterations in the foetal seminiferous cords are also noted after in utero phthalate treatment with the induction of multinucleate gonocytes that contribute to lowered spermatocyte numbers in postnatal animals. The phthalate syndrome of effects on reproductive development has parallels with the reported human testicular dysgenesis syndrome, although no cause and

  1. Parental Educational Attainment and Adult Offspring Personality: An Intergenerational Life Span Approach to the Origin of Adult Personality Traits.

    PubMed

    Sutin, Angelina R; Luchetti, Martina; Stephan, Yannick; Robins, Richard W; Terracciano, Antonio

    2017-03-13

    Why do some individuals have more self-control or are more vulnerable to stress than others? Where do these basic personality traits come from? Although a fundamental question in personality, more is known about how traits are related to important life outcomes than their developmental origins. The present research took an intergenerational life span approach to address whether a significant aspect of the childhood environment-parental educational attainment-was associated with offspring personality traits in adulthood. We tested the association between parents' educational levels and adult offspring personality traits in 7 samples (overall age range 14-95) and meta-analytically combined the results (total N > 60,000). Parents with more years of education had children who were more open, extraverted, and emotionally stable as adults. These associations were small but consistent, of similar modest magnitude to the association between life events and change in personality in adulthood, and were also supported by longitudinal analyses. Contrary to expectations, parental educational attainment was unrelated to offspring Conscientiousness, except for a surprisingly negative association in the younger cohorts. The results were similar in a subsample of participants who were adopted, which suggested that environmental mechanisms were as relevant as shared genetic variants. Participant levels of education were associated with greater conscientiousness, emotional stability, extraversion, and openness and partially mediated the relation between parent education and personality. Child IQ and family income were also partial mediators. The results of this research suggest that parental educational attainment is 1 intergenerational factor associated with offspring personality development in adulthood. (PsycINFO Database Record

  2. Stunted growth, increased mortality, and liver tumors in offspring of polybrominated biphenyl (PBB) dosed sherman rats.

    PubMed

    Groce, D F; Kimbrough, R D

    1984-01-01

    Firemaster FF-1, a polybrominated biphenyl (PBB) mixture, was dissolved in corn oil and given as a dose of 200 mg/kg body weight to Sherman rats on d 7 and 14 of pregnancy. Control rats received equivalent doses of corn oil alone. Selected pups and all dams were killed 1 mo after pups were weaned. A total of 50 male and 50 female offspring per group were followed until they were 2 yr old. The livers of offspring killed at the ages of 2 mo and 2 yr had PBB levels of 2,4 (SD 1.2) and 0.8 (SD 0.65) mg/kg for females and 3.0 (SD 1.6) and 0.6 (SD 0.37) mg/kg for males, respectively. The incidence of hepatocellular carcinomas was 3/51 (5.9%) and 4/41 (9.6%) after 2 yr in females and males, respectively. Hepatocellular carcinomas were not observed among the controls. Neoplastic (hyperplastic) nodules of the liver were present in 9/51 (17.6%) and 2/41 (4.9%) of exposed females and males, respectively, whereas only 2/48 (4.2%) of control females and no control males had neoplastic (hyperplastic) nodules. Body weights were lower in PBB-exposed rats at ages 1, 6, 12, and 24 mo. Survival rates from birth to weaning were lower in PBB-exposed pups (89%) than in controls (98%). Mortality was two times higher in PBB-exposed males (64%) than in control males (32%) after 2 yr. Transplacental PBB exposure and exposure through milk resulted in PBB body burdens in the offspring still measurable at the end of their lifespan. These offspring had increased mortality rates and lower body weights than controls, and they developed hepatocellular carcinomas.

  3. Rat gestation during space flight: outcomes for dams and their offspring born after return to Earth.

    PubMed

    Wong, A M; DeSantis, M

    1997-01-01

    Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

  4. Rat Gestation During Space Flight: Outcomes for Dams and Their Offspring Born After Return to Earth

    NASA Technical Reports Server (NTRS)

    Wong, Andre M.; DeSantis, Mark

    1997-01-01

    Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

  5. Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring.

    PubMed

    Stoker, T E; Robinette, C L; Cooper, R L

    1999-11-01

    The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), TIDA neuronal growth is impaired and elevated PRL levels are present in the prepubertal male. These observations, combined with the finding that alterations in PRL secretion (i.e., hyperprolactinemia) in the adult male rat have been implicated in the development of prostatitis, led us to hypothesize that early lactational exposure to agents that suppress suckling-induced PRL release would lead to a disruption in TIDA development, altered PRL regulation, and subsequent prostatitis in the male offspring. To test this hypothesis, suckling-induced PRL release was measured in Wistar dams treated twice daily with the herbicide atrazine (ATR, by gavage, on PND 1-4 at 0, 6.25, 12.5, 25, and 50 mg/kg body weight), or twice daily with the dopamine receptor agonist bromocriptine (BROM, sc, at 0.052, 0.104, 0.208, and 0.417 mg/kg); BROM is known to suppress PRL release. Similarly, atrazine has also been reported to suppress PRL in adult females. Serum PRL was measured on PND 3 using a serial sampling technique and indwelling cardiac catheters. A significant rise in serum PRL release was noted in all control females within 10 min of the initiation of suckling. Fifty-mg/kg ATR inhibited suckling-induced PRL release in all females, whereas 25 and 12.5 mg/kg ATR inhibited this measure in some dams and had no discernible effect in others. The 6.25 mg/kg dose of ATR was without effect. BROM, used here as a positive control, also inhibited suckling-induced PRL release at doses of 0.104 to 0.417 mg/kg, with no effect at 0.052 mg/kg. To examine the effect of postnatal ATR and BROM on the incidence and severity of inflammation (INF) of the lateral prostate of the offspring, adult males were examined at 90 and

  6. The association of maternal socialization in childhood and adolescence with adult offsprings' sympathy/caring.

    PubMed

    Eisenberg, Nancy; VanSchyndel, Sarah K; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood (between 7-8 and 11-12 years of age) and adolescence (between 13-14 and 17-18 years of age). Adult offsprings' sympathy/caring was assessed 3 times in early adulthood (at ages 19-20 to 23-24 years) and in their mid-20s to 30s (ages 25-26 to 31-32 years). In general, friends' reports of participants' sympathy/concern at ages 25-32 years related positively to mother-reported rational discipline (including inductions) and warmth and support during childhood and adolescence and negatively to mother-reported negative affect during adolescence. Self-reported sympathy/concern during early adulthood was positively related to maternal warmth and support during childhood and almost significantly negatively related to mother-reported negative affect during childhood and adolescence. Most of the relations held when the prior level of self-reported childhood empathy or adolescent sympathy was controlled.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-12-01

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

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

    PubMed

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

    2014-01-01

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

  10. Exposure to the widely used fungicide mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Nellemann, Christine; Kiersgaard, Maria; Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hougaard, Karin Sørig; Hass, Ulla

    2011-04-01

    The widely used fungicide mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100, or 150 mg mancozeb/kg body weight (bw)/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T(4)) levels were measured in dams during gestation. On PND 16, hormone levels and several organ weights were measured in the offspring, whereas motor activity, startle response, and cognitive function were assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams and was therefore reduced to 100 mg/kg bw/day in mid study. T(4) levels showed a dose-dependent and significant decrease in dams from all three dose groups on GD 15, whereas offspring T(4) levels, thyroid weights, and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did, however, reduce T(4) levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affects the developing brain.

  11. Childhood maltreatment in adult offspring of Portuguese war veterans with and without PTSD

    PubMed Central

    Dias, Aida; Sales, Luisa; Cardoso, Rui M.; Kleber, Rolf

    2014-01-01

    Background The colonial war that Portugal was involved in between 1961 and 1974 had a significant impact on veterans and their families. However, it is unclear what the consequences of this war are, in particular with regard to levels of childhood maltreatment (CM) in offspring. Objective Our study aims to analyze the influences of fathers’ war exposure and posttraumatic stress disorder (PTSD) on the offspring's CM and simultaneously test the hypothesis of the intergenerational transmission of father–child CM. Method Cross-sectional data were collected, using the Childhood Trauma Questionnaire—Short Form, from 203 adult children and 117 fathers. Subjects were distributed according to three conditions based on the father's war exposure status: did not participate in war, or non-war-exposed (NW); participated in war, or war-exposed (W); and war-exposed with PTSD diagnosis (WP). The data were examined using correlations, variance/covariance, and regression analyses. Results Children of war veterans with PTSD reported more emotional and physical neglect, while their fathers reported increased emotional and physical abuse exposure during their own childhood. Significant father–child CM correlations were found in the war veteran group but less in the war veteran with PTSD group. Father CM predicted 16% of offspring CM of children of war veterans. Conclusions The father's war-related PTSD might be a risk factor for offspring neglect but potentially a protective one for the father–child abuse transmission. War-exposed fathers without PTSD did transmit their own CM experiences more often. Therefore, father's war exposure and father's war PTSD may each be important variables to take into account in the study of intergenerational transmission of CM. PMID:24505510

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  14. Exercise during rat pregnancy and lactation: maternal effects and offspring growth.

    PubMed

    Courant, G T; Barr, S I

    1990-03-01

    Eighty Sprague-Dawley rats were divided into exercised (E) and sedentary (S) groups. E rats were trained to run on a treadmill (30 m/min, 2 hr/day). Within each group, two subgroups were mated and three served as virgin time controls. Of the mated subgroups, one was terminated within 24 hours of delivery and the other on day 14 of lactation. Subgroups of virgin S and E controls were terminated at times corresponding to the mating, delivery and lactation day 14 of mated rats. MANOVA revealed that exercise significantly affected food intake, body weight and body composition in both virgin and mated animals: generally, E rats ate more, gained more weight, and had less carcass fat than S controls. E rats did not store fat during pregnancy. At parturition, they were 7.0% fat, similar to both E (6.6%) and S (7.6%) controls prior to mating, and less than S rats at parturition (11.9%). Despite diminished fat stores at parturition in E rats, litter size and pup birthweight were similar in E and S rats, as was offspring growth during lactation (mean weights on day 14 of 28.9 g and 29.3 g, respectively). Remaining body fat and increased food intake were adequate to support normal pup growth.

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

    PubMed

    Haghani, M; Shabani, M; Moazzami, K

    2013-10-10

    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.

  16. Locomotor activity and sensory-motor developmental alterations in rat offspring exposed to arsenic prenatally and via lactation.

    PubMed

    Gumilar, Fernanda; Lencinas, Ileana; Bras, Cristina; Giannuzzi, Leda; Minetti, Alejandra

    2015-01-01

    Arsenic (As) is one of the most toxic naturally occurring contaminants in the environment. The major source of human exposure to inorganic As (iAs) is through contaminated drinking water. Although both genotoxicity and carcinogenicity derived from this metalloid have been thoroughly studied, the effects of iAs on the development and function of the central nervous system (CNS) have received less attention and only a few studies have focused on neurobehavioral effects. Thus, in order to characterize developmental and behavioral alterations induced by iAs exposure, pregnant Wistar rats were exposed to 0.05 and 0.10 mg/L iAs through drinking water during gestation and lactation. Sensory-motor reflexes in each pup were analyzed and the postnatal day when righting reflex, cliff aversion and negative geotaxis were recorded. Functional Observational Battery (FOB) and locomotor activity in an open field were assessed in 90-day-old offspring. Results show that rats exposed to low iAs concentrations through drinking water during early development evidence a delay in the development of sensory-motor reflexes. Both FOB procedure and open-field tests showed a decrease in locomotor activity in adult rats. This study reveals that exposure to the above-mentioned iAs concentrations produces dysfunction in the CNS mechanisms whose role is to regulate motor and sensory development and locomotor activity.

  17. DENTAL MINERALIZATION AND SALIVARY ACTIVITY ARE REDUCED IN OFFSPRING OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR)

    PubMed Central

    Elias, Gracieli Prado; dos Santos, Otoniel Antonio Macedo; Sassaki, Kikue Takebayashi; Delbem, Alberto Carlos Botazzo; Antoniali, Cristina

    2006-01-01

    Several pathologies have been diagnosed in children of hypertensive mothers; however, some studies that evaluated the alterations in their oral health are not conclusive. This study analyzed the salivary gland activity and dental mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day-old SHR males and Wistar rats were studied. The salivary flow was evaluated by injection of pilocarpine, the protein concentration and salivary amylase activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel and dentin mineralization of the mandibular incisors was quantified with aid of the microhardness meter. The results were analyzed by the ANOVA or Student's t test (p<0.05). It was noticed that the salivary flow rate (0.026 mL/min/100 g ± 0.002) and salivary protein concentration (2.26 mg/mL ± 0.14) of SHR offspring were reduced compared to Wistar normotensive offspring (0.036 mL/min/100 g ± 0.003 and 2.91 mg/mL ± 0.27, respectively), yet there was no alteration in amylase activity (SHR: 242.4 U/mL ± 36.9; Wistar: 163.8 U/mL ± 14.1). Microhardness was lower both in enamel (255.8 KHN ± 2.6) and dentin (59.9 KHN ± 0.8) for the SHR teeth compared to the Wistar teeth (enamel: 328.7 KHN ± 3.3 and dentin: 67.1 KHN ± 1.0). These results suggest that the SHR offspring are more susceptible to development of pathologies impairing oral health, once they presented lesser flow and salivary protein concentration and lower dental mineralization. PMID:19089272

  18. Effects of prenatal maternal stress by repeated cold environment on behavioral and emotional development in the rat offspring.

    PubMed

    Tazumi, Tooru; Hori, Etsuro; Uwano, Teruko; Umeno, Katsumi; Tanebe, Kyoko; Tabuchi, Eiichi; Ono, Taketoshi; Nishijo, Hisao

    2005-07-01

    It has been reported that many types of stresses, which caused physiological and psychological alterations in dams as prenatal maternal stress, affected behavioral and emotional traits of their offspring. However, effects of environmental temperature changes, which induce various stress responses in both animals and humans, have not been assessed as prenatal maternal stress. Repeated cold stress (RCS) is a type of chronic cold stress in which environmental temperature changes rapidly and frequently several times within a day. In the present study, to investigate effects of chronic maternal stress by the RCS on behavioral and emotional development of the rat offspring (prenatal RCS rats), the RCS stress was loaded to pregnant rats between day 9 and 19 after fertilization. The prenatal RCS rats showed similar locomotor activity in an open field to control rats that were borne by non-stressed pregnant rats. On the other hand, the prenatal RCS rats showed significantly higher startle responses than the control rats in a light enhanced startle paradigm. However, treatment of diazepam decreased the startle responses in the prenatal RCS rats to the same degree as those in the control rats. The results indicated that prenatal RCS affected emotional development of the rat offspring, but not locomotor activity. Comparison of the present results with the previous studies suggests that there might be unknown common mechanisms among different prenatal maternal stresses that induce similar behavioral developmental alteration.

  19. Short- and long-term effects of a maternal low-protein diet on ventilation, O₂/CO₂ chemoreception and arterial blood pressure in male rat offspring.

    PubMed

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

    2014-02-01

    Maternal undernutrition increases the risk of adult arterial hypertension. The present study investigated the short- and long-term effects of a maternal low-protein diet on respiratory rhythm, O₂/CO₂ chemosensitivity and arterial blood pressure (ABP) of the offspring. Male Wistar rats were divided into two groups according to their mothers' diets during gestation and lactation: control (NP, 17% of casein) and low-protein (LP, 8% of casein) groups. Direct measurements of ABP, respiratory frequency (RF), tidal volume (V T) and ventilation (VE), as well as hypercapnia (7% CO₂) and hypoxia (7% O₂) evoked respiratory responses were recorded from the awake male offspring at the 30th and 90th days of life. Blood samples were collected for the analyses of protein, creatinine and urea concentrations. The LP offspring had impaired body weight and length throughout the experiment. At 30 d of age, the LP rats showed a reduction in the concentrations of total serum protein (approximately 24%). ABP in the LP rats was similar to that in the NP rats at 30 d of age, but it was 20% higher at 90 d of age. With respect to ventilatory parameters, the LP rats showed enhanced RF (approximately 34%) and VE (approximately 34%) at 30 d of age, which was associated with increased ventilatory responses to hypercapnia (approximately 21% in VE) and hypoxia (approximately 82% in VE). At 90 d of age, the VE values and CO₂/O₂ chemosensitivity of the LP rats were restored to the control range, but the RF values remained elevated. The present data show that a perinatal LP diet alters respiratory rhythm and O₂/CO₂ chemosensitivity at early ages, which may be a predisposing factor for increased ABP at adulthood.

  20. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    SciTech Connect

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L. . E-mail: leonguo@ha.mc.ntu.edu.tw

    2007-05-15

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.

  1. Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment

    PubMed Central

    Zhao, Qiuying; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Jiang, Wei; Wu, Xiaohui; Yan, Shuo; Chen, Yubo; Peng, Cheng; You, Zili

    2015-01-01

    Despite the potential adverse effects of maternal sleep deprivation (MSD) on physiological and behavioral aspects of offspring, the mechanisms remain poorly understood. The present study was intended to investigate the roles of microglia on neurodevelopment and cognition in young offspring rats with prenatal sleep deprivation. Pregnant Wistar rats received 72 h sleep deprivation in the last trimester of gestation, and their prepuberty male offspring were given the intraperitoneal injection with or without minocycline. The results showed the number of Iba1+ microglia increased, that of hippocampal neurogenesis decreased, and the hippocampus-dependent spatial learning and memory were impaired in MSD offspring. The classical microglial activation markers (M1 phenotype) IL-1β, IL-6, TNF-α, CD68 and iNOS were increased, while the alternative microglial activation markers (M2 phenotype) Arg1, Ym1, IL-4, IL-10 and CD206 were reduced in hippocampus of MSD offspring. After minocycline administration, the MSD offspring showed improvement in MWM behaviors and increase in BrdU+/DCX+ cells. Minocycline reduced Iba1+ cells, suppressed the production of pro-inflammatory molecules, and reversed the reduction of M2 microglial markers in the MSD prepuberty offspring. These results indicate that dysregulation in microglial pro- and anti-inflammatory activation is involved in MSD-induced inhibition of neurogenesis and impairment of spatial learning and memory. PMID:25830666

  2. Protective effects of maternal methyl donor supplementation on adult offspring of high fat diet-fed dams.

    PubMed

    Jiao, Fei; Yan, Xiaoshuang; Yu, Yuan; Zhu, Xiao; Ma, Ying; Yue, Zhen; Ou, Hailong; Yan, Zhonghai

    2016-08-01

    Obesity has become a global public health problem associated with metabolic dysfunction and chronic disorders. It has been shown that the risk of obesity and the DNA methylation profiles of the offspring can be affected by maternal nutrition, such as high-fat diet (HFD) consumption. The aim of this study was to investigate whether metabolic dysregulation and physiological abnormalities in offspring caused by maternal HFD can be alleviated by the treatment of methyl donors during pregnancy and lactation of dams. Female C57BL/6 mice were assigned to specific groups and given different nutrients (control diet, Control+Met, HFD and HFD+Met) throughout gestation and lactation. Offspring of each group were weaned onto a control diet at 3 weeks of age. Physiological (weight gain and adipose composition) and metabolic (plasma biochemical analyses) outcomes were assessed in male and female adult offspring. Expression and DNA methylation profiles of obesogenic-related genes including PPAR γ, fatty acid synthase, leptin and adiponectin were also detected in visceral fat of offspring. The results showed that dietary supplementation with methyl donors can prevent the adverse effects of maternal HFD on offspring. Changes in the expression and DNA methylation of obesogenic-related genes indicated that epigenetic regulation may contribute to the effects of maternal dietary factors on offspring outcomes.

  3. Perinatal Nicotine Exposure Induces Myogenic Differentiation, But Not Epithelial–Mesenchymal Transition in Rat Offspring Lung

    PubMed Central

    Sakurai, Reiko; Liu, Jie; Gong, Ming; Bo, Ji; Rehan, Virender K.

    2016-01-01

    Summary Objective Perinatal nicotine exposure alters offspring lung structure and function; however, the underlying mechanisms remain incompletely understood. Whether epithelial– mesenchymal transition (EMT), a known contributor to pulmonary pathology, occurs following moderate perinatal nicotine exposure is not known. Methods Pregnant, pair-fed Sprague Dawley rat dams received either placebo (diluent) or nicotine [1 mg/kg, subcutaneously] once daily from embryonic day (e) 6 to postnatal day (PND) 21. Generation 1 (F1) and 3 (F3) offspring lungs were isolated at PND 21, and using Western analysis, q-RT-PCR and immunohistochemistry examined for evidence of EMT. To gain further supportive evidence for nicotine-induced EMT, embryonic day 19 primary rat lung alveolar type II (ATII) cells were cultured and treated with nicotine for 24 hr. Results Protein levels of α-smooth muscle actin, fibronectin, and calponin (myogenic differentiation markers) increased significantly. However, surfactant proteins B and C, and cholinephosphate cytidylyltransferase- α (epithelial cell markers), as well as the typical markers of EMT, E-cadherin, N-cadherin, and fibroblast specific protein (FSP)-1, in both F1 and F3 generation lungs, showed no significant change between the nicotine exposed and control dams. Immunostaining of lung sections and data from in vitro treated ATII cells strongly supported the Western data. Conclusions Enhanced myogenic molecular profile, without evidence of EMT, as evidenced by the absence of the loss of E-cadherin or gains in N-cadherin and FSP-1, suggest that perinatal nicotine exposure does not result in EMT, but it leads to myogenesis, which predominantly accounts for the lung phenotype seen in perinatally nicotine exposed rat offspring. PMID:27183179

  4. Maternal fructose-intake-induced renal programming in adult male offspring.

    PubMed

    Tain, You-Lin; Wu, Kay L H; Lee, Wei-Chia; Leu, Steve; Chan, Julie Y H

    2015-06-01

    Nutrition in pregnancy can elicit long-term effects on the health of offspring. Although fructose consumption has increased globally and is linked to metabolic syndrome, little is known about the long-term effects of maternal high-fructose (HF) exposure during gestation and lactation, especially on renal programming. We examined potential key genes and pathways that are associated with HF-induced renal programming using whole-genome RNA next-generation sequencing (NGS) to quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3-month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) during the entire period of pregnancy and lactation. Male offspring exhibited programmed hypertension at 3 months of age. Maternal HF intake modified over 200 renal transcripts from nephrogenesis stage to adulthood. We observed that 20 differentially expressed genes identified in 1-day-old kidney are related to regulation of blood pressure. Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be potential key genes/pathways contributing to renal programming and hypertension. Collectively, our NGS data suggest that maternal HF intake elicits a defective adaptation of interrelated EDHFs during nephrogenesis which may lead to renal programming and hypertension in later life. Moreover, our results highlight genes and pathways involved in renal programming as potential targets for therapeutic approaches to prevent metabolic-syndrome-related comorbidities in children with HF exposure in early life.

  5. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.

    PubMed

    Dahlhoff, M; Pfister, S; Blutke, A; Rozman, J; Klingenspor, M; Deutsch, M J; Rathkolb, B; Fink, B; Gimpfl, M; Hrabě de Angelis, M; Roscher, A A; Wolf, E; Ensenauer, R

    2014-02-01

    Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition.

  6. Effects of Prenatal Dexamethasone on the Rat Pituitary Gland and Gonadotropic Cells in Female Offspring.

    PubMed

    Ristić, Nataša; Severs, Walter; Nestorović, Nataša; Jarić, Ivana; Manojlović-Stojanoski, Milica; Trifunović, Svetlana; Pendovski, Lazo; Milosević, Verica

    2016-01-01

    Glucocorticoids have a strong influence on growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids may retard fetal growth and alter developmental processes in sensitive tissues. The aim of this study was to specifically determine whether prenatal exposure to dexamethasone (Dx) altered normal development and function of pituitary gonadotropic cells in neonatal, infant and peripubertal female offspring. On day 16 of pregnancy, rat dams received 1.0 mg Dx/kg body weight (BW) s.c., followed by 0.5 mg Dx/kg BW on days 17 and 18 of gestation. Control gravid females received the same volume of saline. Female offspring were sacrificed on days 5, 16 and 38 after delivery. The volume of the pituitary gland estimated using Cavalieri's principle was significantly reduced (p < 0.05). Using a fractionator-physical disector method, we found reduced total numbers of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells (p < 0.05), accompanied by a decrease (p < 0.05) in serum concentrations of FSH and LH, while the relative intensity of FSH and LH immunofluorescence remained unchanged in neonatal, infant and peripubertal female offspring prenatally exposed to Dx. The data document that overexposure to Dx during fetal development evokes developmental programming of the female reproductive system at the pituitary cellular level, which may be associated with impaired reproductive function.

  7. Maternal arachidonic acid supplementation improves neurodevelopment of offspring from healthy and diabetic rats.

    PubMed

    Zhao, Jinping; Del Bigio, Marc R; Weiler, Hope A

    2009-01-01

    Maternal diabetes may compromise infant arachidonic acid status and development. This study tested if maternal arachidonic acid supplementation improves neurodevelopment in rat offspring. Dams were randomized into 6 groups using a 3x2 design: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed either control or an arachidonic acid (0.5% of fat) diet throughout reproduction. Offspring were tested on post-natal days 3 and 5 for righting response, days 7 and 9 for negative geotaxis, day 14 for wire hanging endurance, days 18 and 24 for rota rod endurance, and day 28 for Morris water maze performance. Only the poorly controlled group had impaired day 7 geotaxis and day 18 rota rod performance (p<0.02), but this improved with maternal arachidonic acid supplementation (p<0.0006). Arachidonic acid improved the wire hanging endurance (p=0.0003) and water maze latency (p=0.0021), suggesting enhanced neurodevelopment in all offspring.

  8. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    PubMed

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  9. Genotoxic effects of prenatal exposure to levetiracetam during pregnancy on rat offsprings.

    PubMed

    Tural, Sengul; Tekcan, Akin; Elbistan, Mehmet; Karakuş, Nevin; Ozyurek, Hamit; Kara, Nurten

    2015-01-01

    Levetiracetam is a new-generation antiepileptic drug initially approved as an adjunctive treatment for patients with refractory partial seizures and is now also used as a monotherapy. The aim of this study was to evaluate the genotoxic effects of levetiracetam exposure during pregnancy on rat offsprings. In this study, we used the newborn pups of rats exposed to levetiracetam during pregnancy. Thirty Sprague-Dawley rats were divided into three groups. The mother rats of groups 1 and 2 were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d) from gestational days 1 to 18 during pregnancy. Group 3 (control group) was not treated with any drug. In vivo sister chromatid exchange (SCE) induction and in vivo micronucleus formation were assessed. Bone marrow from rat pups were used for investigation. As a result of this study, levetiracetam exposure did not alter SCE frequencies or the mean of number of micronuclei in the prenatal period (p>0.05). Levetiracetam did not cause miscarriage during pregnancy in mother rats. The present study highlighted fetal safety after prenatal exposure to levetiracetam.

  10. Maternal nicotine exposure and fetal programming of vascular oxidative stress in adult offspring.

    PubMed

    Lim, Rebecca; Sobey, Christopher G

    2011-11-01

    Despite the well-known harmful effects, many women continue to smoke throughout pregnancy. Consequently, nicotine replacement therapy (NRT) - which has been developed as a pharmacotherapy for smoking cessation - has been used as an alternative to smoking during pregnancy. However, like cigarette smoking, NRT results in biologically significant levels of nicotine crossing the placenta, leading to both fetal and neonatal exposure to nicotine, and yet, NRT safety during pregnancy has not been extensively evaluated. There is now evidence from studies in rats that maternal nicotine exposure throughout gestation results in fetal programming of vascular oxidative stress in the offspring during adulthood. This phenomenon involves vascular dysfunction mediated by reactive oxygen species in association with decreased superoxide dismutase activity and increased Nox2-NADPH oxidase expression in the vascular wall. If this phenomenon also occurs in humans, either smoking or NRT use during pregnancy may represent a novel risk factor for the unborn that results in accelerated cardiovascular disease in their adulthood.

  11. Gestational Chronodisruption Impairs Hippocampal Expression of NMDA Receptor Subunits Grin1b/Grin3a and Spatial Memory in the Adult Offspring

    PubMed Central

    Vilches, Nelson; Spichiger, Carlos; Mendez, Natalia; Abarzua-Catalan, Lorena; Galdames, Hugo A.; Hazlerigg, David G.; Richter, Hans G.; Torres-Farfan, Claudia

    2014-01-01

    Epidemiological and experimental evidence correlates adverse intrauterine conditions with the onset of disease later in life. For a fetus to achieve a successful transition to extrauterine life, a myriad of temporally integrated humoral/biophysical signals must be accurately provided by the mother. We and others have shown the existence of daily rhythms in the fetus, with peripheral clocks being entrained by maternal cues, such as transplacental melatonin signaling. Among developing tissues, the fetal hippocampus is a key structure for learning and memory processing that may be anticipated as a sensitive target of gestational chronodisruption. Here, we used pregnant rats exposed to constant light treated with or without melatonin as a model of gestational chronodisruption, to investigate effects on the putative fetal hippocampus clock, as well as on adult offspring’s rhythms, endocrine and spatial memory outcomes. The hippocampus of fetuses gestated under light:dark photoperiod (12:12 LD) displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock-controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B-3A-3B. In contrast, in the hippocampus of fetuses gestated under constant light (LL), these oscillations were suppressed. In the adult LL offspring (reared in LD during postpartum), we observed complete lack of day/night differences in plasma melatonin and decreased day/night differences in plasma corticosterone. In the adult LL offspring, overall hippocampal day/night difference of gene expression was decreased, which was accompanied by a significant deficit of spatial memory. Notably, maternal melatonin replacement to dams subjected to gestational chronodisruption prevented the effects observed in both, LL fetuses and adult LL offspring. Collectively, the present data point to adverse effects of gestational chronodisruption on long-term cognitive function; raising challenging questions about the consequences of shift work during

  12. Seasonal variations of Substance P in the striatum of the female rat are affected by maternal and offspring pinealectomy.

    PubMed

    Díaz, E; Vázquez, N; Fernández, C; Durand, D; Lasaga, M; Debeljuk, L; Díaz, B

    2011-04-01

    The effect of pinealectomy (PIN-X) and PIN-X+melatonin treatment during pregnancy (PIN-X+MEL) 100μg/100g body weight on Substance P (SP) in the striatum was investigated in offspring female rats. Female offspring were divided into control and PIN-X at the neonatal period, and studied at days 31 and 60. PIN-X mother/control offspring showed a positive influence on striatal SP values in winter, at both ages and in spring at day 31. However, this effect of maternal PIN-X was not observed in summer or fall. The effect of PIN-X on the offspring showed a positive effect in spring at day 31 and summer at the two ages studied. This effect was not observed in fall or winter. Two generations, PIN-X mother/PIN-X offspring, altered the effect of mother or offspring PIN-X and decreased the SP values in winter, spring and summer. Only striatal SP at day 60 in fall was increased. In two generations PIN-X, the striatal SP values were similar to those observed in control mother/control offspring. The effect of PIN-X+MEL treatment on mothers during pregnancy was inhibitory for the intact offspring and stimulatory for PIN-X offspring. In conclusion, the results indicate that maternal and offspring PIN-X seem to exert a rotative and positive seasonal influence from winter to spring to summer. Two generations PIN-X disrupted this rotative circuit and in fall a compensatory discharge of SP was observed.

  13. Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

    SciTech Connect

    Axelstad, Marta; Boberg, Julie; Hougaard, Karin Sorig; Christiansen, Sofie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Nellemann, Christine; Lund, Soren Peter; Hass, Ulla

    2011-02-01

    Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T{sub 4}), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T{sub 4}) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T{sub 4} deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the

  14. Effects of beer, wine, whiskey, and ethanol on pregnant rats and their offspring.

    PubMed

    Abel, E L; Dintcheff, B A; Bush, R

    1981-04-01

    Pregnant rats were intubated twice daily throughout gestation with the equivalent of 3 gm/kg of alcohol in the form of either beer, wine, whiskey, or 95% ethanol. Control animals received vehicle. All animals were pair-fed to those receiving ethanol. Offspring were removed from their biological mothers immediately following birth and were nursed by nondrug-treated mothers. Animals in each of the four alcohol-treated groups weighed significantly less than the animals in the control group at birth and at 22 days of age and also performed significantly worse on a Rotarod at 17 days; differences among the four alcohol-treated groups were not significant for any of these measures. Results suggest that congeners present in these alcohol beverages do not potentiate the effects of alcohol on embryonic/fetal development in rats administered this alcohol dose.

  15. Effects of bracken fern (Pteridium aquilinum L Kuhn) feeding during the development of female rats and their offspring.

    PubMed

    Gerenutti, M; Spinosa, H de S; Bernardi, M M

    1992-08-01

    Bracken fern (Pteridium aquilinum L Kuhn), is widely food in many parts of the world; the toxic effects have been demonstrated on many species of animals, and both carcinogenicity and enzootic hematuria has been studied. We investigated the effects of feeding bracken fern on the development of female rats and their offspring. The plant was fed as 30% of the normal diet on an ad libitum basis. Bracken fern did not modify the weight gain of the female rats during development, nor affect estrus cycle duration or milk production, the plant did reduce female fertility and weight gain during pregnancy. It also adversely affected physical and neurobehavioral development in the offspring.

  16. Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    PubMed

    Carratù, M R; Cagiano, R; Desantis, S; Labate, M; Tattoli, M; Trabace, L; Cuomo, V

    2000-08-25

    Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

  17. Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines.

    PubMed

    McBride, Shawna M; Culver, Bruce; Flynn, Francis W

    2008-09-01

    This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6-8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors.

  18. [Experimental behavioral tests using monkey and rat offspring born from mothers exposed perinatally to EDCs].

    PubMed

    Yoshikawa, Yasuhiro

    2005-06-01

    Purpose of this study is to conduct risk assessment of EDCs for the development of CNS in humans by extrapolation from the results of behavioral tests in rats and monkeys. Our hypotheses on the mechanism which gives an adverse effect of EDCs to the developing neural systems are as follows. Thyroid hormone (TH) disrupting chemicals induce deterioration of neural development and estrogen (E2) agonistic chemicals may disturb apoptosis of fetal neural cells resulting in injury of normal neural circuit. The strategy of this study is a bottom up system; for example, basic information was obtained by an experiment using rats and then an experiment using monkey was designed to adapt the results from rats. The monkey experiment data will be assessed in comparison with human behavior. The tactics of this study are, however, a top down system. It is neural behaviors which are an end point evaluation that are primarily performed. They are mother-infant interactions, social behaviors, open field test, memory and learning tests, etc. As for analysis of the mechanism of EDCs' adverse effect, we tried two methods: one is an in vivo drug biased test which interferes with the monoamine oxidase (MAO) system and the other is an in vitro primary neural cell culture. EDCs including BPA, NP, propylthiouracil (PTU) and PCB-OH are injected orally to pregnant rats from gestation day 3 (GD3) to post natal day 21 (PND21) at weaning and their offspring were tested. On the other hand TCDD, BPA and PCB effect are assessed in rhesus monkey or cynomolgus monkey offspring. The study is still continuing and we will present the results obtained to date.

  19. Effect of a high-fat diet on diabetic mother rats and their offspring through three generations.

    PubMed

    Nasu, Ritsuko; Seki, Koji; Nara, Misa; Murakami, Masami; Kohama, Tomoko

    2007-08-01

    Pregnant diabetic Wistar rats were fed a high-fat diet starting at the first gestational day. The effect of the high-fat diet on the growth of the female, her offspring, and the offspring's offspring was studied. Pregnant rats (first generation) were divided into the Diabetic streptozotocin-induced group and the control group. Diabetic streptozotocin-induced rats and control rats were fed either a control diet (5% fat in diet) or high-fat diet (32% fat in diet), and observed up to the third generation. In each generation, after weaning, the pups were fed the respective diet. The fat content was mainly animal lard. Diabetic rats fed the high-fat diet were infertile, and the pregnant first-generation and diabetic rats fed the control diet had a stillbirth rate of 27.5 +/- 22.0% (mean +/- SE). In the first generation, the diabetic rats fed the control diet had a significantly lower body weight increase during the pregnancy than the control rats fed the control diet. The second-generation diabetic rats fed the control diet had a high blood glucose level at birth, and their triglyceride level was higher than that in the other two groups. The third-generation diabetic rats fed the control diet had a triglyceride level higher than that of control rats. Delivery was most difficult in diabetic rats fed the high-fat diet. Pups of diabetic rats fed the control diet had growth retardation and increased blood glucose levels. We conclude that when the mother rat had diabetes, the next generation was also affected.

  20. Transfer of individual chlorobiphenyls from adult female grey seals to their offspring via milk

    SciTech Connect

    Green, N.J.L.; Jones, K.C.; Pomeroy, P.P.; Harwood, J.

    1994-12-31

    Branded individual grey seals (Halichoerus grypus) have been monitored on the Isle of May, Scotland over a three year period to investigate the influence of polychlorinated biphenyls (PCBs) on their health. Simultaneous sampling of milk, blood and adipose tissue from weaning mothers has enabled a detailed analysis of the release of individual chlorobiphenyls from a mother seal`s fat reserves, and their availability to the seal`s offspring through lactation. Transfer coefficients have been calculated for 22 individual congeners for their mobilization from adipose to blood, and for their incorporation from blood into milk. The overall transfer from blubber to milk decreased with increasing chlorination from ca 0.6 for tetra- to < 0.1 for octa- and nona-chlorinated biphenyls. Fat samples from 21 pups of the study adults were analyzed for the same chlorobiphenyl congeners. No congener selectivity was observable for the combined uptake and storage processes of these chlorobiphenyls by the pups.

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

    PubMed

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

    2016-03-23

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

  2. Parental longevity and 7-year changes in blood pressures in adult offspring.

    PubMed

    Zureik, Mahmoud; Galan, Pilar; Bertrais, Sandrine; Courbon, Dominique; Czernichow, Sébastien; Blacher, Jacques; Ducimetière, Pierre; Safar, Michel E; Hercberg, Serge

    2005-08-01

    In this report, we examined the cross-sectional and the 7-year longitudinal changes in blood pressures in adult offspring according to parental longevity. A population of volunteers free of symptomatic cardiovascular diseases who participated to the Supplementation en Vitamines et en Minéraux Antioxydants (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were analyzed separately. The prevalence of hypertension at baseline in subjects whose father died at <65 years of age, in those whose fathers were alive by age 65 but died by 80 years of age, and in those whose fathers were alive by age 80 was respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0), 125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the mean systolic blood pressure increases in the 3 groups of paternal longevity were respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In subjects without hypertension at baseline, hypertension occurred during the follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate analyses adjusted for baseline or changes in cardiovascular risk factors did not modify these results. In contrast, there was no relationship between maternal longevity and blood pressure measurements in either cross-sectional or longitudinal analyses. This study suggests that paternal premature death was associated with accelerated progression of systolic blood pressure and higher occurrence of hypertension in offspring. These results indicate that there are dynamic and continuous processes linking paternal longevity to blood pressure in adults.

  3. Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring.

    PubMed

    Gur, Tamar L; Shay, Lena; Palkar, Aditi Vadodkar; Fisher, Sydney; Varaljay, Vanessa A; Dowd, Scot; Bailey, Michael T

    2016-12-24

    Recent studies demonstrate that exposure to stress changes the composition of the intestinal microbiota, which is associated with development of stress-induced changes to social behavior, anxiety, and depression. Stress during pregnancy has also been related to the emergence of these disorders; whether commensal microbes are part of a maternal intrauterine environment during prenatal stress is not known. Here, we demonstrate that microbiome changes are manifested in the mother, and also found in female offspring in adulthood, with a correlation between stressed mothers and female offspring. Alterations in the microbiome have been shown to alter immune responses, thus we examined cytokines in utero. IL-1β was increased in placenta and fetal brain from offspring exposed to the prenatal stressor. Because IL-1β has been shown to prevent induction of brain derived neurotrophic factor (BDNF), we examined BDNF and found a reduction in female placenta and adult amygdala, suggesting in utero impact on neurodevelopment extending into adulthood. Furthermore, gastrointestinal microbial communities were different in adult females born from stressed vs. non-stressed pregnancies. Adult female offspring also demonstrated increased anxiety-like behavior and alterations in cognition, suggesting a critical window where stress is able to influence the microbiome and the intrauterine environment in a deleterious manner with lasting behavioral consequences. The microbiome may be a key link between the intrauterine environment and adult behavioral changes.

  4. Pathogenesis and epidemiology of Brucellosis in Yellowstone bison: serologic and culture results from adult females and their offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this prospective study was to follow the natural course of Brucella abortus infection in cohorts of seropositive and seronegative female bison and their offspring in Yellowstone National Park over a 5 year period. Specimens were collected from 53 adult, female bison at least once a...

  5. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

    EPA Science Inventory

    Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

  6. Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations

    PubMed Central

    He, Nan; Kong, Qiao-Qiao; Wang, Jun-Zuo; Ning, Shu-Fen; Miao, Yi-Long; Yuan, Hong-Jie; Gong, Shuai; Cui, Xiang-Zhong; Li, Chuan-Yong; Tan, Jing-He

    2016-01-01

    While effects of gestational, neonatal or adolescent stress on psychological alterations in progeny have been extensively studied, much less is known regarding the effects of adult pre-gestational life events on offspring behavior. Although full siblings often display behavioral differences, whether the different parental life events prior to different pregnancies contribute to these behavioral differences among siblings is worth studying. In this study, male and female adult mice were restrained for 60 days before mating with unstressed or stressed partners. F1 offspring were examined for anxiety or mated to generate F2. Both F1 females and males from restrained mothers and/or fathers showed significantly reduced anxiety and serum cortisol and increased mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor compared to control offspring from unstressed parents. Similar behavioral and molecular changes were also observed in F2 females and males. Although restraint of adolescent mice reduced anxiety in F1 of both sexes, social instability of them increased anxiety predominantly in F1 females. Thus, adult pre-gestational restraint reduced offspring’s anxiety across generations; different stressors on parents may cause different phenotypes in offspring; individual behaviors can depend on adult life experiences of parents. PMID:28000794

  7. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.

    EPA Science Inventory

    Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and ovi...

  8. Cadmium, iron and zinc interaction and hematological parameters in rat dams and their offspring.

    PubMed

    Mikolić, Anja; Schönwald, Neala; Piasek, Martina

    2016-12-01

    The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0-21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams' litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group). This procedure enabled to discern the effects of gestational, lactational and gestational plus lactational Cd exposure until weaning in F1 offspring. Elements were analyzed by atomic absorption spectrometry; hematological parameters manually; and histopathological changes by light microscopy. Gestational plus lactational exposure in Cd-exposed dams and their offspring increased Cd and decreased Fe levels, increased Zn in dams and decreased Zn and body weights in 11- and 21-day pups. In 21-day weanling pups, decreased red blood cell (RBC) count, hemoglobin and hematocrit values and increased reticulocytes in peripheral blood were also found with concomitant histopathological finding of extramedullary hematopoiesis in the liver. In cross-fostered pups with gestational exposure (CCd pups), Fe in the liver decreased on day 11 and Zn increased in the kidney on day 21 whereas in pups with lactational exposure (CdC pups) Zn in the brain decreased on day 11 and Fe decreased in the liver and brain on day 21. Regardless of exposure cessation at weaning, in offspring with gestational plus lactational exposure (Cd-exposed) body weights, kidney and brain Fe levels and RBC and hemoglobin remained decreased in blood until puberty. Furthermore Zn levels increased in the liver, kidney and brain. It was concluded that gestational plus lactational Cd exposure caused decreases in Fe and Zn levels

  9. Effects of autoimmune NGF deprivation in the adult rabbit and offspring.

    PubMed

    Johnson, E M; Gorin, P D; Osborne, P A; Rydel, R E; Pearson, J

    1982-05-20

    An experimental autoimmune approach to the production of nerve growth factor deprivation, which we have previously described in the rat and guinea pig, has been applied to the rabbit. This species was chosen for study because of several potential advantages. The rabbit produces large litters and has a relatively short gestation period. More importantly, rabbits generate high titers of antibody against mouse NGF and large amounts of maternal antibody are passively transferred to the developing rabbit fetus compared to most other species, particularly the rat. The sympathetic nervous system of adult rabbit immunized against mouse NGF underwent degeneration with up to an 85% decrease in neuronal numbers in the superior cervical ganglion after 10 months of immunization, thus providing further evidence that NGF is required for the survival of mature sympathetic neurons. Despite the fact that newborn rabbits born to anti-NGF producing mothers had much higher titers of anti-NGF than did rats, the effects on the developing sympathetic and sensory nervous systems were not found to be any greater than in rats. Reductions in norepinephrine levels in the heart and spleen of adult rabbits born to anti-NGF producing mothers were greater than in small intestine. Prenatal exposure to maternal anti-NGF caused reductions (up to 70%) in the number of neurons in the dorsal root ganglia. Substance-P immunoreactivity was reduced in the substantia gelatinosa of the spinal cord of rabbit exposed to maternal anti-NGF. These changes, however, were not greater than seen in the rat. We conclude that although the rabbits offers some advantage in the study of the effects of NGF deprivation in the adult animal, it appears less well suited than the rat or guinea pig to the study of the effects of NGF deprivation on development.

  10. Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

    PubMed

    El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

    2010-06-10

    Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in

  11. Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

    PubMed

    Dobson, Christine C; Thevasundaram, Kersh; Mongillo, Daniel L; Winterborn, Andrew; Holloway, Alison C; Brien, James F; Reynolds, James N

    2014-11-01

    Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling

  12. Associations Between Substance Use Disorders and Major Depression in Parents and Late Adolescent-Emerging Adult Offspring: An Adoption Study

    PubMed Central

    Marmorstein, Naomi R.; Iacono, William G.; McGue, Matt

    2012-01-01

    Aims To examine whether major depressive disorder (MDD) and substance use disorders (SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)) in parents predicted increased risk for these disorders in late adolescent–emerging adult offspring and, specifically, the extent to which the pattern of risk differed for adopted and non-adopted youth. Participants Late adolescent and emerging adult participants from the Sibling Interaction and Behavior Study (mean age=18.8), a community-based investigation of adopted and non-adopted adolescents, and their parents (adoptive parents of adopted youth, biological parents of non-adopted adolescents) were included. Measurements Structured interviews were used to assess these disorders. Findings (1) when the same disorder in parents and adolescents was examined, parental MDD was associated with increased risk for MDD among both adopted (p<.001) and non-adopted (p<.01) adolescents; in contrast, SUDs were associated with increased risk for the same SUD in non-adopted offspring (all p<.01). (2) When cross-SUD effects were examined, for the most part, each SUD was associated with increased risk for other SUDs among non-adopted but not adopted offspring (most p<.05). (3) When MDD-SUD associations were examined, parental ND and CUDs predicted increased risk for MDD in non-adopted (p<.001), but not adopted, adolescents. These effects tended to remain significant when adjusting for within-person comorbidity (p<.05). Conclusions Major depressive disorder in parents appears to be a risk factor for late adolescent-emerging adult major depressive disorder but not substance use disorder in offspring, with this risk being environmentally mediated. Substance use disorder in parents appears, via genetic mediation, to increase risk of substance use disorder in adolescent offspring, and cannabis and nicotine use disorders in parents similarly contribute to major depressive disorder in those

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

    PubMed Central

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

    2014-01-01

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

  14. The influence of parental divorce and alcohol abuse on adult offspring risk of lifetime suicide attempt in the United States.

    PubMed

    Alonzo, Dana; Thompson, Ronald G; Stohl, Mahlki; Hasin, Deborah

    2014-05-01

    The influences of parental divorce and alcohol abuse on adult offspring lifetime suicide attempt have not been examined in national data. This study analyzed data from the 2001-2002 NESARC to estimate main and interaction effects of parental divorce and alcohol abuse on lifetime suicide attempt. Adjusted for controls, parental divorce and parental alcohol abuse independently increased odds of lifetime suicide attempt. The effect of parental divorce was not significantly moderated by parental alcohol abuse. Further research is needed to examine whether additional parental and offspring psychiatric and substance use covariates attenuate the association between parental divorce and lifetime suicide attempt.

  15. Prenatal and early postnatal exposure to high-saturated-fat diet represses Wnt signaling and myogenic genes in offspring rats.

    PubMed

    Yang, Ke-Feng; Shen, Xiu-Hua; Cai, Wei

    2012-08-01

    The prenatal and early postnatal period is a key developmental window for nutrition status, and high-fat exposure in this period has been shown to be associated with type 2 diabetes, obesity and other features of metabolic disorders later in life. The present study was designed to investigate the underlying molecular mechanisms and role of relative genes involved in this process. We investigated the impact of prenatal and early postnatal exposure to a high-saturated-fat diet on the regulation of the Wnt signaling pathway and myogenic genes in skeletal muscle of rat offspring as well as the serum and muscle physiological outcomes. Timed-pregnant Sprague-Dawley rats were fed either a control (C, 16% kcal fat) or high-saturated-fat diet (HF, 45% kcal fat) throughout gestation and lactation. After weaning, female offspring were fed a control diet to generate two offspring groups: control diet-fed offspring of control diet-fed dams (C/C) and control diet-fed offspring of HF diet-fed dams (HF/C). The serum glucose of the HF/C offspring (5.58 ± 0.26 mmol/L) was significantly higher than that of C/C offspring (4.97 ± 0.28 mmol/L), and the Homeostasis Model Assessment-Insulin Resistance of HF/C offspring (2.00 ± 0.11) was also significantly higher when compared with C/C (1.84 ± 0.09). Furthermore, HF/C offspring presented excessive intramuscular fat accumulation (1.8-fold, P < 0.05) and decreased muscle glycogen (1.3-fold, P < 0.05), as well as impairment of muscle development at the age of 12 weeks. Meanwhile, we observed the repression of Wnt/β-catenin signaling and myogenic genes in HF/C offspring. The present study indicates that prenatal and early postnatal exposure to a high-saturated-fat diet suppresses the development of skeletal muscle and myogenic genes via Wnt/β-catenin signaling, and the inappropriate muscle development could potentially contribute to the predisposition of offspring to develop metabolic-syndrome-like phenotype in adulthood.

  16. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    PubMed

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R; Newman, John W; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

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

    PubMed

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

    2014-06-01

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

  18. Methamphetamine exposure during pregnancy at pharmacological doses produces neurodevelopmental and behavioural effects in rat offspring.

    PubMed

    McDonnell-Dowling, Kate; Donlon, Michelle; Kelly, John P

    2014-06-01

    In recent years methamphetamine (MA) use has become more prevalent, and of particular concern is its growing popularity of MA among women of childbearing age. However, to date, studies examining MA effects on the developing offspring in laboratory animals are limited. Thus, the aim of this study was to determine if in utero MA exposure in rats at pharmacological doses can have a negative impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral gavage from gestational day 7 to 21. Maternal body weight, food and water consumption were recorded daily. A range of standard neurodevelopment parameters was examined in the offspring during the neonatal period. There were no neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in fact, there were enhancements of neurodevelopment in some parameters at this low dose. However, exposure to the 1.25mg/kg MA dose resulted in significant impairments in surface righting reflex and forelimb grip in both sexes. Exposure to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital distance in males, and in both sexes resulted in delayed fur appearance and eye opening, impairments in surface righting reflex and negative geotaxis, and a reduction in body length. In conclusion, this study demonstrates that pharmacologically relevant doses of MA can have profound dose-related effects on neonatal outcome. If extrapolated to the clinical scenario this will give cause for concern regarding the risks associated with this drug of abuse at relatively low doses.

  19. 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...

  20. LATE GESTATIONAL EXPOSURE TO THE FUNGICIDE PROCHLORAZ DELAYS THE ONSET OF PARTURITION AND CAUSES REPRODUCTIVE MALFORMATIONS IN MALE RAT OFFSPRING

    EPA Science Inventory

    Late gestational exposure to the fungicide prochloraz delays the onset of parturition and causes reproductive malformations in male rat offspring.
    Nigel C. Noriega, Joseph Ostby, Christy Lambright, Vickie S. Wilson, and L. Earl Gray Jr.,

    Prochloraz (PZ) is an imidazol...

  1. Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

    PubMed

    Bolton, Jessica L; Auten, Richard L; Bilbo, Staci D

    2014-03-01

    Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner.

  2. Parental Neuropathic Pain Influences Emotion-Related Behavior in Offspring Through Maternal Feeding Associated with DNA Methylation of Amygdale in Rats.

    PubMed

    Zhong, Tao; Zhang, Yanfeng; Guo, Qulian; Yang, Yong; Yan, Jianqin; Dai, Ruping; Wu, Hui

    2015-06-01

    Chronic neuropathic pain has currently become a remarkable public health concern, considerably damaging not only the physiological but also the psychological aspects of humans. This study investigated whether neuropathic pain affects maternal care and assessed the effect of parental neuropathic pain on the development of neuropathic pain and emotion among offspring. Our results showed that mother rats suffered from chronic constriction injury (CCI) exhibited defective maternal care. The offspring fed by CCI mother rats (own or cross-fed) showed a significant increase in anxiety and anxiety-related behavior compared with that fed by sham-operated mother rats. The offspring fed by CCI mother rats also displayed decreased oxytocin expression in their supraoptic nucleus than that fed by sham-operated mother rats. Moreover, DNA methyltransferase (DNMT)1 expression in the amygdale was increased, whereas DNMT3a and DNMT3b expressions remained the same in offspring fed by CCI mother rats, as detected with immunohistochemistry and western blot analysis. In addition, the total DNA methylation in amygdale was upregulated in offspring fed by CCI mother rats. Considering the above findings, the data of this study suggest that parental neuropathic pain influences emotion-related behavior in offspring through maternal feeding behavior rather than through genetic factors and pregnancy experience that was associated with DNA methylation of amygdale in offspring.

  3. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

    PubMed Central

    Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

    2015-01-01

    BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

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

    PubMed

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

    2016-01-15

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

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

    PubMed

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

    2015-01-21

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

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

    PubMed

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

    2010-04-01

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

  7. Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring.

    PubMed

    Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

    2016-01-01

    Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring.

  8. Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring

    PubMed Central

    Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

    2016-01-01

    Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring. PMID:27847471

  9. Effects of zinc depletion and repletion during lactation on rat dams and their offspring

    SciTech Connect

    Dibi, K.

    1985-01-01

    The effects of feeding 5 mg Zn/kg, 12 mg Zn/kg, 50 mg Zn/kg in egg white diets and 50 mg Zn/kg in defatted glandless cottonseed diet on postnatal growth and tissue zinc concentrations of dams and neonates were investigated. One or more of the following tissues were obtained on days 7, 14, 21, and 56 for analyses: femur, liver, brain, testes, spleen, and/or blood. Dams fed the cottonseed diet weighted more than dams fed the egg white diets. Dams fed zinc in cottonseed diet had higher blood zinc concentrations than dams fed zinc in the egg white diets. Dams and the offspring fed 50 mg zn/kg egg white diet had higher femur zinc levels than dams and the offspring fed 50 mg Zn/kg in the cottonseed diet. There was no difference in the weight gain/loss of dams fed 50 mg Zn/kg or 12 mg Zn/kg egg white diets. Femur zinc concentrations of pups suckling dams fed 50 mg Zn/kg egg white were higher than femur zinc concentrations of pups suckling dams fed 12 mg Zn/kg egg white diet. Body weights and tissue zinc concentrations of the neonates suckling dams fed 5 mg Zn/kg egg white diet and then repleted with zinc in either egg white or cottonseed diet were similar. There was complete recovery when rats were fed 5 mg Zn/kg and then repleted with zinc at 50 mg Zn/kg level. Therefore, the protein source did not have statistically significantly different effects on zinc availability to the rats.

  10. Positive long-term outcomes from presuckling calcium supplementation in lactating rats and the offspring.

    PubMed

    Suntornsaratoon, Panan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2015-06-01

    Adequate dietary calcium intake and the enhanced intestinal calcium absorption in lactating mothers have long been postulated to prevent maternal bone loss and benefit neonatal bone growth. We recently showed that calcium supplementation just before breastfeeding efficiently alleviated lactation-induced bone loss in dams as well as increased milk calcium concentration, which led to higher bone mineral density (BMD) in the newborns. Herein, we further elaborated in detail how presuckling calcium supplements worked in lactating rats and how they benefited bone growth in the offspring. As revealed by bone histomorphometry, presuckling supplement with calcium alone reduced the osteoclast surface and active erosion surface, leading to an increase in trabecular thickness without changes in trabecular separation or number in dams. The beneficial effects of presuckling calcium supplements, particularly the regimen containing glucose and galactose that enhanced intestinal calcium absorption, were found to last for 3 mo postweaning, although it could not restore estrogen-deficient osteopenia induced by ovariectomy. Regarding the neonatal benefits, pups nursed by calcium-supplemented dams exhibited increases in trabecular BMD, which could be observed even at the age of 27 wk. Bone elongation was also greater in pups of calcium-supplemented dams, which was due possibly to accelerated growth plate chondrocyte turnover. It could be concluded that calcium supplements markedly diminished the lactation-induced osteopenia in dams and positively affected BMD and bone elongation in growing rats. Therefore, presuckling calcium supplementation in lactating mothers is an effective strategy for promoting a long-lasting high bone density for both mother and the offspring.

  11. Bcl-2 gene family expression in the brain of rat offspring after gestational and lactational dioxin exposure.

    PubMed

    Chang, Shwu-Fen; Sun, Yu-Yo; Yang, Liang-Yo; Hu, Ssu-Yao; Tsai, Shih-Ying; Lee, Wen-Sen; Lee, Yi-Hsuan

    2005-05-01

    Recent epidemiological studies have shown that dioxin, a persistent organic pollutant, is related to cognitive and behavioral abnormalities in the offspring of exposed cohort. In order to investigate the possible impact of dioxin in survival gene expression during brain development, we established an animal model of gestational and lactational dioxin-exposed rat offspring. The expressions of dioxin-responsive gene cytochrome P450 1A1 (CYP1A1), apoptotic gene Bax, and anti-apoptotic genes Bcl-2 and Bcl-xL were examined in rat liver and brains using Western blot analysis and RT-PCR. The results showed that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (2 microg/kg body weight through oral delivery) at gestation day 15 resulted in an increase of Bcl-xL in offspring male liver and cerebral cortex, but a decrease in female offspring. In contrast, the expression of Bcl-xL in the cerebellum was decreased in male, but increased in female. Bcl-2, another anti-apoptotic gene, was also downregulated in P0 female liver, cerebral cortex, but was not observed in male. In the 4-month-old offspring, however, the Bcl-2 protein levels in the liver and cerebellum of both male and female pups were higher in the TCDD group as compared with the control group. However, the Bcl-2 level in the cerebral cortex of TCDD-treated groups was higher than the control group only in female but not male offspring at 4 months old. The expression of Bax showed no significant changes upon TCDD exposure at P0 stage, but was significantly reduced in the 4-month-old male cortex. These results indicate that early exposure of dioxin could affect the development of certain brain regions with gender difference, in terms of its differential effect on expressions of Bcl-xL, Bcl-2, and Bax.

  12. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet.

    PubMed

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts.

  13. Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

    PubMed Central

    Fujita, Yuko; Ishima, Tamaki; Hashimoto, Kenji

    2016-01-01

    Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects. PMID:27853241

  14. [The effect of methyl-containing supplements during pregnancy on the phenotypic modification of offspring hair color in rats].

    PubMed

    Prasolova, L A; Trut, L N; Os'kina, I N; Gulevich, R G; Pliusnina, I Z; Vsevolodov, E B; Latypov, I F

    2006-01-01

    The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.

  15. A maternal high fat diet programmes endothelial function and cardiovascular status in adult male offspring independent of body weight, which is reversed by maternal conjugated linoleic acid (CLA) supplementation.

    PubMed

    Gray, Clint; Vickers, Mark H; Segovia, Stephanie A; Zhang, Xiaohuan D; Reynolds, Clare M

    2015-01-01

    Maternal high fat intake during pregnancy and lactation can result in obesity and adverse cardio-metabolic status in offspring independent of postnatal diet. While it is clear that maternal high fat intake can cause hypertension in adult offspring, there is little evidence regarding the role of dietary interventions in terms of reversing these adverse effects. Conjugated linoleic acid (CLA) is an omega 6 fatty acid with beneficial effects in obesity and metabolic status. However, the impact of CLA supplementation in the context of pregnancy disorders and high fat diet-induced developmental programming of offspring cardio-metabolic dysfunction has not been investigated. We have utilised a model of maternal overnutrition to examine the effects of CLA supplementation on programmed endothelial dysfunction during adulthood. Female Sprague-Dawley rats were fed either a purified control diet (CON) or purified control diet supplemented with 1% CLA (of total fat), a purified high fat (HF) diet (45%kcal from fat) and a purified HF diet supplemented with 1% CLA (of total fat) (HFCLA). All dams were fed ad libitum throughout pregnancy and lactation. Offspring were fed a standard chow diet from weaning (day 21) until the end of the study (day 150). Systolic blood pressure (SBP) was measured at day 85 and 130 by tail cuff plethysmography. At day 150, offspring mesenteric vessels were mounted on a pressure myograph and vascular responses to agonist-induced constriction and endothelium-dependent vasodilators were investigated. SBP was increased at day 85 and 130 in HF and HFCLA adult male offspring compared to CON and CLA groups with no effect of CLA supplementation. An overall effect of a maternal HF diet was observed in adult male vessels with a reduced vasoconstrictor response to phenylephrine and blunted vasodilatory response to acetylcholine (ACh). Furthermore, HF and HFCLA offspring displayed a reduction in nitric oxide pathway function and an increased compensatory EDHF

  16. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  17. Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

    PubMed

    Aerts, L; Van Assche, F A

    2001-01-01

    Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation.

  18. Mortality in Adult Offspring of Immigrants: A Swedish National Cohort Study

    PubMed Central

    Manhica, Hélio; Toivanen, Susanna; Hjern, Anders; Rostila, Mikael

    2015-01-01

    Background Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective. Methods We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents who were either Swedish born or had received residency in Sweden before school age (<7 years) were defined as “offspring of immigrants.” We used Cox regression models to examine the association between parental country of birth and mortality between 1990 and 2008, with adjustment for education, income, age and family type. Results Male offspring of immigrants from the Middle East (HR:2.00, CI:1.66-2.26), other non-European countries (HR:1.80, CI:1.36-2.36) and Finland (HR:1.56, CI:1.48-1.65) showed an age-adjusted excess mortality risk from all causes of death when compared to offspring with Swedish-born parents. Income, but not education, greatly attenuated these increased mortality risks. No excess mortality rates were found among female offspring of immigrants, with the exception of external cause of death among offspring of Finnish immigrants. Conclusion The study demonstrates high mortality rates in male offspring of immigrants from Finland and non-European countries that are associated with economic, but not educational, disadvantage. No increased mortality rates were found among female offspring of immigrants. Future studies are needed to explain this gender differential and why income, but not education, predicts mortality in male offspring of immigrants. PMID:25706297

  19. Adult helpers increase the recruitment of closely related offspring in the cooperatively breeding rifleman

    PubMed Central

    Briskie, James V.; Hatchwell, Ben J.

    2016-01-01

    Indirect fitness benefits gained through kin-selected helping are widely invoked to explain the evolution of cooperative breeding behavior in birds. However, the impact of helpers on productivity of helped broods can be difficult to determine if the effects are confounded by territory quality or if the benefit of helpers is apparent only in the long term. In riflemen Acanthisitta chloris, helping and group membership are effectively decoupled as adult helpers are individuals that have dispersed from their natal territory and live independently from breeders in “kin neighborhoods.” Nevertheless, helpers direct their care toward close relatives, suggesting that helping provides indirect fitness benefits. The aim of this study was to examine the benefits of helpers to recipient offspring in the rifleman, investigating both short- and long-term effects. The total amount of food delivered to nestlings in helped broods was greater than that received by broods without helpers. This did not result in any short-term increase in nestling mass or nestling body condition nor was there any reduction in length of the nestling period at helped nests. However, helpers were associated with a significant increase in juvenile recruitment, with twice the proportion of fledglings surviving to the next breeding season from helped broods relative to unhelped broods. Thus, helpers gain indirect fitness by improving the survival of kin, and in contrast to a previous study of riflemen, we conclude that kin selection has played a key role in the evolution of cooperative breeding in this species. PMID:28028377

  20. Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring

    ERIC Educational Resources Information Center

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    The article highlights the field of epigenetics and its relevance in determining the effects of maternal nurturing on behavioral patterns in offsprings. Results concluded that maternal behavior influences the offspring's behavior to stress in adulthood and the effects are transgenerational through epigenetic mechanisms.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    PubMed

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-02-25

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  3. In vivo longitudinal micro-CT study of bent long limb bones in rat offspring.

    PubMed

    De Schaepdrijver, Luc; Delille, Peter; Geys, Helena; Boehringer-Shahidi, Christian; Vanhove, Christian

    2014-07-01

    Micro-computed X-ray tomography (micro-CT) has been reported as a reliable method to assess ex vivo rat and rabbit fetal skeletons in embryo-fetal developmental toxicity studies. Since micro-CT is a non-invasive imaging modality it has the potential for longitudinal, in vivo investigation of postnatal skeletal development. This is the first paper using micro-CT to assess the reversibility of drug-induced bent long bones in a longitudinal study from birth to early adulthood in rat offspring. Analysis of the scans obtained on postnatal Day 0, 7, 21 and 80 showed complete recovery or repair of the bent long limb bones (including the scapula) within the first 3 weeks. When assessing risk the ability to demonstrate recovery is highly advantageous when interpreting such transient skeletal change. In summary, in vivo micro-CT of small laboratory animals can aid in non-clinical safety assessment, particularly for specific mechanistic purposes or to address a particular concern in developmental biology.

  4. Effect of red peppers (Capsicum frutescens) intake during gestation on thermonociceptive response of rat offspring.

    PubMed

    Pellicer, F; Picazo, O; León-Olea, M

    2001-03-15

    Oral administration of aqueous red pepper (Capsicum frutescens, Cf) solution and low capsaicin (8-methyl-N-vanillyl-6-nonenamide) doses during gestation produces an increase in the latency of the thermonociceptive escape response of rat offspring. The present work shows that different amounts of Cf (10%, 25% and 50%) incorporated to normal food of gestating rats modify in a dose-dependent manner the flexion reflex latency (R), as well as the latency of appearance of antialgesic behaviours expressed as paw lick (P) and escape response (E) using the hot plate test (53 degrees C+/-0.5 degrees C). The latency of the same parameters was tested in the same subjects 55 days later to determine the persistence of this effect. Results show an increase in latency of the three parameters R, P and E in all experimental groups with respect to controls. Animals (Cf, 25% group) tested 55 days after the first test exhibited latencies similar to controls, which suggests that the process is reversible.

  5. The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Apoptosis in Rat Offspring's Eye Retina

    PubMed Central

    Khordad, Elnaz; Fazel, Alireza; Ebrahimzadeh Bideskan, Alireza

    2013-01-01

    Introduction: Lead toxicity induces retinal cell apoptosis. Vitamin C and garlic may decrease lead-induced apoptosis. This study was undertaken to investigate vitamin C and garlic protective effects on lead-induced apoptosis in eye retina. Methods: Pregnant Wistar rats (n = 72) were divided randomly into 9 groups: (L) treated rats with lead acetate in drinking water and (L+AA) with leaded water and vitamin C intraperitoneally;(L+G), the rats received leaded-water and garlic juice via gavage; (L+AA+G) treated rats with leaded water, ascorbic acid, and garlic juice, (AA) with ascorbic acid, and (G) with garlic juice; (AA+G) treated rats with vitamin C and garlic juice and (Sh) with tap water plus normal hydrogen chloride (HCl) and glucose; normal (N). After 21-day lactation, blood lead level (BLL) in rats was measured, and then their offspring and the rat offspring's eyes were removed and processed for using TUNEL method. TUNEL positive cells in the eye retina were counted and all groups were compared. Results: BLL increased in L group compared to the control groups and decreased significantly in L + G, L + AA, and L+ AA + G groups compared to L group (P<0.05). TUNELL positive cell number in eye retina significantly increased in L group compared to control groups (P<0.05) and decreased in L+ G, L+ AA, and L+AA + G groups compared to L group (P<0.05). Conclusion: Garlic juice and ascorbic acid administration during pregnancy and lactation may protect lead-induced apoptosis in rat offspring's eye retina. PMID:23999717

  6. The Preventive Effect of Zuogui Wan on Offspring Rats' Impaired Glucose Tolerance Whose Mothers Had Gestational Diabetes Mellitus

    PubMed Central

    Feng, Qianjin; Niu, Xin; Xu, Kaixia; Wang, Yingli; Wang, Jinlong; Mao, Yingqiu; Gao, Shuangrong

    2016-01-01

    In this experiment, we used streptozotocin (STZ) to establish a model of gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats. After pregnancy, offspring rats were divided into 4 groups: control group, high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were fed with high fat and sugar diet. Rats in control group were fed the basic diet. The means of 2hPG were higher than 7.8 mmol·L−1 and lower than 11.1 mmol·L−1 on the rats of GDM group on week 15, and IGT models were successful. Body weight, abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM group. The level of adiponectin in Zuogui Wan GDM group was significantly higher than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a preventive effect on the offsprings' IGT induced by high fat and sugar diet. PMID:27034700

  7. Supplementing the maternal diet of rats with butyrate enhances mitochondrial biogenesis in the skeletal muscles of weaned offspring.

    PubMed

    Huang, Yanping; Gao, Shixing; Jun, Guo; Zhao, Ruqian; Yang, Xiaojing

    2017-01-01

    The present study aimed to investigate the effects of maternal dietary butyrate supplementation on energy metabolism and mitochondrial biogenesis in offspring skeletal muscle and the possible mediating mechanisms. Virgin female rats were randomly assigned to either control or butyrate diets (1 % butyrate sodium) throughout gestation and lactation. At the end of lactation (21 d), the offspring were killed by exsanguination from the abdominal aorta under anaesthesia. The results showed that maternal butyrate supplementation throughout gestation and lactation did not affect offspring body weight. However, the protein expressions of G-protein-coupled receptors (GPR) 43 and 41 were significantly enhanced in offspring skeletal muscle of the maternal butyrate-supplemented group. The ATP content, most of mitochondrial DNA-encoded gene expressions, the cytochrome c oxidase subunit 1 and 4 protein contents and the mitochondrial DNA copy number were significantly higher in the butyrate group than in the control group. Meanwhile, the protein expressions of type 1 myosin heavy chain, mitochondrial transcription factor A, PPAR-coactivator-1α (PGC-1α) and uncoupling protein 3 were significantly increased in the gastrocnemius muscle of the treatment group compared with the control group. These results indicate for the first time that maternal butyrate supplementation during the gestation and lactation periods influenced energy metabolism and mitochondrial biogenesis through the GPR and PGC-1α pathways in offspring skeletal muscle at weaning.

  8. Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring

    PubMed Central

    Li, Na; Li, Yongmei; Gao, Qinqin; Li, Dawei; Tang, Jiaqi; Sun, Miao; Zhang, Pengjie; Liu, Bailin; Mao, Caiping; Xu, Zhice

    2015-01-01

    Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2+-activated K+ (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca2+ sensitivity of BKCa channels. BKCa α-subunit expression was unchanged, BKCa β1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca2+]i fluorescence and vasoconstriction testing showed reduced Ca2+, leading to diminished BKCa activation via ryanodine receptor Ca2+ release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins. PMID:26277840

  9. Offspring-exposure reduces depressive-like behaviour in the parturient female rat.

    PubMed

    Pawluski, Jodi L; Lieblich, Stephanie E; Galea, Liisa A M

    2009-01-30

    In women, breastfeeding generally results in reductions in anxiety and increased positive mood. However, approximately 10-15% of women experience depressed mood and increased anxiety during the first year postpartum. Recent research has demonstrated that offspring-exposure is important for the reduction in behaviours related to depression and anxiety in the mother. It remains to be determined whether these effects are due to factors related to pregnancy and/or pup-exposure, are associated with the degree of maternal behaviour by the mother towards offspring, or persist after weaning. To address these questions the present study used four groups of female rats; primiparous, nulliparous, primip-no-pups (primiparous females with pups permanently removed), and sensitized females. Depressive- and anxiety-like behaviours were assessed 1 week after weaning/pup-exposure (4 weeks after birth for primip-no-pups animals) using the forced swim test for measures of depressive-like behaviour, and the open field test and elevated plus maze for measure of anxiety-like behaviour. Results demonstrate that primiparous females without pup-exposure have increased depressive-like, but not anxiety-like, behaviour compared to primiparous and sensitized females. In addition, kyphotic nursing by primiparous mothers was negatively related to behavioural measures of depression and anxiety. From this work it is clear that pup-exposure is important for reductions in depressive-like behaviour in parturient females. Further research is needed to determine the extent of these changes and the neural and hormonal correlates of these events.

  10. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

    PubMed

    Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-02-01

    Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.

  11. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    PubMed Central

    2016-01-01

    Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats. PMID:27230461

  12. Inhibition of the osteogenic differentiation of mesenchymal stem cells derived from the offspring of rats treated with caffeine during pregnancy and lactation.

    PubMed

    Reis, Amanda Maria Sena; Ocarino, Natália de Melo; Boeloni, Jankerle Neves; Gomes, Dawidson Assis; Goes, Alfredo Miranda; Ferreira, Andrea da Fonseca; Serakides, Rogéria

    2016-01-01

    Caffeine is an alkaloid that is widely consumed due to its presence in drugs, coffee, tea, and chocolate. This compound passes to offspring through the placenta and milk; can cause teratogenic mutations; and reduces the formation, growth, and mass of bone. Because mesenchymal stem cells (MSCs) are responsible for generating the entire skeleton, we hypothesized that these cells are targets of caffeine. This study evaluated the osteogenic differentiation of MSCs derived from the offspring of rats treated with caffeine during pregnancy and lactation. Twenty-four adult Wistar rats were randomly divided into four groups, including one control group and three experimental groups treated with 25, 50, or 100 mg/kg of caffeine. At weaning, three 21-day-old pups from each dam in each group were euthanized for extraction of bone marrow cells for in vitro tests. Caffeine doses of 50 and 100 mg/kg significantly reduced the activity of alkaline phosphatase at 7, 14, and 21 days and the expression of collagen I at 21 days. However, the expression of gene transcripts for alkaline phosphatase, Runx-2, and bone sialoprotein, as well as the synthesis of mineralization nodules, decreased significantly in all groups treated with caffeine. The expression of osteocalcin was significantly reduced only in the group treated with 50 mg/kg caffeine. The caffeine that passes from the mother to the offspring during pregnancy and lactation reduces the osteogenic differentiation of MSCs. We propose that this reduction in the osteogenic potential of MSCs may be involved in the pathogenesis of osteopenia resulting from caffeine consumption.

  13. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-03

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  14. Assessment of growth and metabolism characteristics in offspring of dehydroepiandrosterone-induced polycystic ovary syndrome adults

    PubMed Central

    Huang, Ying; Gao, Jiang-Man; Zhang, Chun-Mei; Zhao, Hong-Cui; Qiao, Jie

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity, which may have significant implications for pregnancy outcomes and long-term health of women. Daughters born to PCOS mothers constitute a high-risk group for metabolic and reproductive derangements, but no report has described potential growth and metabolic risk factors for such female offspring. Hence, we used a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS to study the mechanisms underlying the pathology of PCOS by investigating the growth, developmental characteristics, metabolic indexes and expression profiles of key genes of offspring born to the models. We found that the average litter size was significantly smaller in the DHEA group, and female offspring had sustained higher body weight, increased body fat and triglyceride content in serum and liver; they also exhibited decreased energy expenditure, oxygen consumption and impaired glucose tolerance. Genes related to glucolipid metabolism such as Pparγ, Acot1/2, Fgf21, Pdk4 and Inhbb were upregulated in the liver of the offspring in DHEA group compared with those in controls, whereas Cyp17a1 expression was significantly decreased. However, the expression of these genes was not detected in male offspring. Our results show that female offspring in DHEA group exhibit perturbed growth and glucolipid metabolism that were not observed in male offspring. PMID:27798284

  15. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

    SciTech Connect

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  16. Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats.

    PubMed

    Kawaguchi, Maiko; Irie, Kaoru; Morohoshi, Kaori; Watanabe, Gen; Taya, Kazuyoshi; Morita, Masatoshi; Kondo, Yasuhiko; Imai, Hideki; Himi, Toshiyuki

    2009-10-01

    Isobutyl-paraben (IBP), one of the most widely used preservatives, exhibits estrogenic activity. In this study, we analyzed the effects of maternal IBP treatment on the emotional behavior and learning performance in mature offspring. Pregnant female Sprague-Dawley rats were treated with IBP via a subcutaneous Silastic capsule. Consequently, the offspring were exposed to IBP during gestation through the placentae, and before weaning through the milk. Male and female offspring were tested for emotional behavior in an open field and in an elevated plus maze at five and six weeks old, respectively. IBP-exposed male (but not female) rats spent less time in the open arms of the elevated plus maze. At 11 weeks old, all females were gonadectomized and treated chronically with 17beta-estradiol or cholesterol by Silastic capsules; all males were kept intact. They were tested for learning performance in a passive avoidance test and a Morris water maze. IBP exposure impaired the performance of males in the passive avoidance test. These findings suggest that male rats are more affected by early exposure to IBP than female rats. IBP affects their adult behavior including anxiety and learning abilities.

  17. The effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus

    PubMed Central

    Ataei, Maryam Lale; Ebrahimzadeh-bideskan, Ali Reza

    2014-01-01

    Objective(s): The aim of this study was to investigate the effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus. Materials and Methods: Fifty pregnant wistar rats were randomly divided into five groups: 1- nano-silver (N.S) group; 30 mg/kg of N.S treated via gavage. 2- Control (C) group, administrated with distilled water via gavage. 3- N.S and garlic (N.S+G) group; N.S (30 mg/kg) and garlic juice (1 ml/100 g) treated via gavage simultaneously. 4- Garlic group (G); garlic juice (1 ml/100 g) administrated via gavage, 5- normal (N) without any intervention. All the interventions were done during pregnancy (21 days). Finally, the brains of rat offspring were removed to use for nano-silver level measurement and TUNEL staining. The mean of TUNEL positive cell numbers per unit area (NA) in different regions of hippocampus were compared in all animal groups. Results: The results revealed a significant increase of hippocampus nano-silver level in N.S and N.S+G groups comparing to N group (P<0.05) and a significant decrease in nano-silver level in N.S+G group comparing to N.S group (P<0.01). The number of TUNEL positive cells in the CA1, CA3, and DG fields of rat offspring hippocampus increased in N.S and N.S+G groups comparing to other ones, and also reduced significantly in N.S+G group comparing to N.S group (¥ P< 0.01). Conclusion: Our results showed that co-administration of nano-silver and garlic during pregnancy may lead to reduce nano-silver induced apoptotic cells in their offspring hippocampus. PMID:25140202

  18. Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring.

    PubMed

    Melancia, Francesca; Servadio, Michela; Schiavi, Sara; Campolongo, Patrizia; Giusti-Paiva, Alexandre; Trezza, Viviana

    2017-03-15

    Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated. To address this issue, we used a validated animal model of prenatal hypothyroidism based on the administration of the thyroid peroxidase inhibitor methimazole (MMI, 0.02g/100ml in tap water) to rat dams from gestational day 9 up to delivery. The offspring was tested in behavioral tasks during infancy (PNDs 5, 9, 13) and adolescence (PND 35-40) to capture some of the core and associated symptoms of ASD. MMI-exposed pups were able to vocalize as controls when separated from the nest, and showed intact social discrimination abilities in the homing behavior test. At adolescence, the offspring from both sexes did not show an anxious-phenotype in the elevated plus maze and showed intact object recognition. However, MMI-exposed male rats showed increased novelty-directed exploratory behaviors: they solicited their partner to play more and showed more interest for novel rather than familiar objects compared to control rats. Our results show that prenatal MMI-induced hypothyroidism does not cause in the rat offspring behaviors that resemble core and associated ASD symptoms, like deficits in communication and social interaction and anxiety.

  19. Effect of vitamin D supplementation during pregnancy on the Th1/Th2 cell balance of rat offspring.

    PubMed

    Chen, Wen-Jia; Hou, Xue-Jing; Yang, Shu-Fen; Yin, Xin-Hua; Ren, Lihong

    2014-05-01

    Vitamin D has important functions in the immune system, and it may suppress the proliferation of T helper (Th) cells and modulate their cytokine production. In this study, we aimed to investigate the effects of maternal supplementation with different doses of vitamin D on the allergy status of the offspring. We gave pregnant female rats a low dose (48000IU/kg, equal to 800IU/d in human) and a high dose (240000IU/kg,equal to 4000IU/d in human) of vitamin D3 intramuscular injection on gestation day (GD)17, and we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of immune responsive cytokines including IL-4, IgE, and interferon gamma (IFN-gamma) in the offspring. On postnatal day (PND) 21, plasma IL-4 levels were elevated by 10.43% (p < 0.01) in the offspring from the high dose vitamin D3 group compared with the control group. And offspring plasma IL-4 levels in the low dose group decreased by 7.27% (p < 0.05) compared with the control dose group. We found that the offspring of mothers given a low dose of vitamin D3 had a 6.17% (p < 0.01) decrease in their plasma IgE levels compared to control animals, but the high dose of vitamin D3 showed no effect. The serum 25(OH)D3 levels were negatively correlated with the IL-4 (r = -0.561, p < 0.01) and IgE (r = -0.421, p < 0.05) levels of the offspring from the low dose group. In the lung tissues of the offspring of the high dose group, we observed thickening of the alveolar septa and more inflammatory cells compared with the control group and low dose group. Thickened alveolar septa were also found in the lung tissues of the offspring from the control group. We conclude that high dose vitamin D3 maternal supplementation during pregnancy induced an imbalance of Th1 and Th2 cells in their offspring resulting allergic and inflammatory response.

  20. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2007-12-15

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

  1. Windscapes shape seabird instantaneous energy costs but adult behavior buffers impact on offspring

    PubMed Central

    2014-01-01

    Background Windscapes affect energy costs for flying animals, but animals can adjust their behavior to accommodate wind-induced energy costs. Theory predicts that flying animals should decrease air speed to compensate for increased tailwind speed and increase air speed to compensate for increased crosswind speed. In addition, animals are expected to vary their foraging effort in time and space to maximize energy efficiency across variable windscapes. Results We examined the influence of wind on seabird (thick-billed murre Uria lomvia and black-legged kittiwake Rissa tridactyla) foraging behavior. Airspeed and mechanical flight costs (dynamic body acceleration and wing beat frequency) increased with headwind speed during commuting flights. As predicted, birds adjusted their airspeed to compensate for crosswinds and to reduce the effect of a headwind, but they could not completely compensate for the latter. As we were able to account for the effect of sampling frequency and wind speed, we accurately estimated commuting flight speed with no wind as 16.6 ms?1 (murres) and 10.6 ms?1 (kittiwakes). High winds decreased delivery rates of schooling fish (murres), energy (murres) and food (kittiwakes) but did not impact daily energy expenditure or chick growth rates. During high winds, murres switched from feeding their offspring with schooling fish, which required substantial above-water searching, to amphipods, which required less above-water searching. Conclusions Adults buffered the adverse effect of high winds on chick growth rates by switching to other food sources during windy days or increasing food delivery rates when weather improved. PMID:26019870

  2. Prenatal stress enhances severity of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring via inflammatory pathways.

    PubMed

    Ho, H; Lhotak, S; Solano, M E; Karimi, K; Pincus, M K; Austin, R C; Arck, P

    2013-02-01

    Atherosclerosis is the underlying cause of cardiovascular disease and stroke. Endothelial cell dysfunctions are early events in atherosclerosis, resulting in the recruitment of circulating monocytes. The immune system can elicit an inflammatory response toward the atherosclerotic lesion, thereby accelerating lesion growth. Risk factors for atherosclerosis include hypertension, smoking, stress perception or low birth weight. As prenatal stress challenge decreases the birth weight and affects the offspring's postnatal immune response, we aimed to investigate whether prenatal stress contributes to the development of atherosclerosis in mice. Syngenic pregnant apolipoprotein E-deficient (apoE-/-) dams were exposed to sound stress on gestation days 12.5 and 14.5. The presence and size of atherosclerotic plaques in the offspring at the age of 15 weeks was evaluated by histomorphology, accompanied by flow cytometric analysis of the frequency and phenotype of monocytes/macrophages and regulatory T (Treg) cells in the blood. Further, cytokine secretion of peripheral blood lymphocytes was analyzed. In response to prenatal stress challenge, an increased frequency of large atherosclerotic plaques was detectable in apoE-/- offspring, which was particularly profound in females. Prenatal stress also resulted in alterations of the offspring's immune response, such as a decreased frequency of Treg cells in blood, alterations of macrophage populations in blood and an increased secretion of inflammatory cytokines. We provide novel evidence that prenatally stressed adult offspring show an increased severity of atherosclerosis. As Treg cells are key players in dampening inflammation, the observed increase in atherosclerosis may be due to the lack of Treg cell frequency. Future interdisciplinary research is urgently required to understand the developmental origin of prenatal stress-induced atherosclerosis. The availability of our model may facilitate and foster such research endeavors.

  3. Modulation of lipid metabolism by n-3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring.

    PubMed

    Soulimane-Mokhtari, Nassima A; Guermouche, Baya; Yessoufou, Akadiri; Saker, Myrieum; Moutairou, Kebirou; Hichami, Aziz; Merzouk, Hafida; Khan, Naim A

    2005-09-01

    The time course of changes in lipid metabolism by dietary n-3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n-3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.

  4. Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression.

    PubMed

    Zhang, X G; Zhang, H; Liang, X L; Liu, Q; Wang, H Y; Cao, B; Cao, J; Liu, S; Long, Y J; Xie, W Y; Peng, D Z

    2016-08-19

    Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were performed on the offsprings 30 days after birth. The results showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of whole-genome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

  5. Maternal lead exposure produces long-term enhancement of dopaminergic reactivity in rat offspring.

    PubMed

    Szczerbak, Grazyna; Nowak, Przemysław; Kostrzewa, Richard M; Brus, Ryszard

    2007-10-01

    To determine the effect of prenatal lead exposure on brain monoaminergic systems, pregnant rats were given tap water containing 250 ppm lead acetate, for the duration of pregnancy, while tap water without lead (Pb(2+)) was substituted at birth. Control rats were derived from dams that consumed tap water during pregnancy, and had no exposure to lead afterwards. At 12 weeks after birth, Pb(2+) content of brain cortex was increased 3- to 4-fold (P < 0.05). At this time the endogenous striatal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were 19% lower in Pb(2+) exposed rats (P < 0.05), while there was no change in the striatal level of dopamine (DA), noradrenaline, 3,4-dihydroxyphenylglycol, serotonin (5-HT) and 5-hydroxyindoleacetic acid (HPLC/ED). Also there was no change in these monoamines and metabolites in the prefrontal cortex of Pb(2+) exposed rats. However, turnover of 5-HT in prefrontal cortex, as indicated by 5-hydroxytryptophan accumulation 30 min after acute treatment with the decarboxylase inhibitor NSD-1015 (100 mg/kg IP), was lower in the Pb(2+) exposed rats. In the striatum AMPH-induced (1 mg/kg IP) turnover of DA, evidenced as L-DOPA accumulation after NSD-1015, was increased to a lesser extent in the Pb(2+) exposed rats (P < 0.05). The nitric oxide synthase inhibitor 7-nitroindazole (10 mg/kg IP) attenuated the latter effect, indicating that neuronal NO mediates this AMPH effect, at least in part. Moreover, DA D(2) receptor sensitivity developed in Pb(2+) exposed rats, as evidenced by enhanced quinpirole-induced yawning activity and enhanced quinpirole-induced locomotor activity (each, P < 0.05). These findings indicate that ontogenetic exposure to lead can have consequences on monoaminergic neuronal function at an adult stage of life, generally promoting accentuated behavioral effects of direct and indirect monoaminergic agonists, and related to increased dopamine turnover in basal ganglia.

  6. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    PubMed

    Huang, Yuejun; Lai, Huihong; Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Chen, Yunbin; Ma, Lian

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  7. Maternal consumption of low-isoflavone soy protein isolate alters hepatic gene expression and liver development in rat offspring.

    PubMed

    Won, Sae Bom; Han, Anna; Kwon, Young Hye

    2017-04-01

    In utero environment is known to affect fetal development. Especially, the distinct fetal programming of carcinogenesis was reported in offspring exposed to maternal diets containing soy protein isolate (SPI) or genistein. Therefore, we investigated whether maternal consumption of low-isoflavone SPI or genistein alters hepatic gene expression and liver development in rat offspring. Female Sprague-Dawley rats were fed a casein diet, a low-isoflavone SPI diet or a casein diet supplemented with genistein (250 mg/kg diet) for 2 weeks before mating and throughout pregnancy and lactation. Male offspring were studied on postnatal day 21 (CAS, SPI and GEN groups). Among 965 differentially expressed hepatic genes related to maternal diet (P<.05), the expression of 590 was significantly different between CAS and SPI groups. Conversely, the expression of 88 genes was significantly different between CAS and GEN groups. Especially, genes involved in drug metabolism were significantly affected by the maternal diet. SPI group showed increased cell proliferation, reduced apoptosis and activation of the mTOR pathway, which may contribute to a higher relative liver weight compared to other groups. We observed higher serum homocysteine levels and lower global and CpG site-specific DNA methylation of Gadd45b, a gene involved in cell proliferation and apoptosis, in SPI group compared to CAS group. Maternal SPI diet also reduced histone H3-Lysine 9 (H3K9) trimethylation and increased H3K9 acetylation in offspring. These results demonstrate that maternal consumption of a low-isoflavone SPI diet alters the hepatic gene expression profile and liver development in offspring possibly by epigenetic processes.

  8. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

  9. Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring.

    PubMed

    Yan, C-G; Rincón-Cortés, M; Raineki, C; Sarro, E; Colcombe, S; Guilfoyle, D N; Yang, Z; Gerum, S; Biswal, B B; Milham, M P; Sullivan, R M; Castellanos, F X

    2017-01-17

    Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.

  10. Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats' hippocampus.

    PubMed

    Lu, Xiaobo; Jin, Cuihong; Yang, Jinghua; Liu, Qiufang; Wu, Shengwen; Li, Dandan; Guan, Yangyang; Cai, Yuan

    2013-01-01

    Oxidative stress and apoptosis facilitation in the developing central nervous system (CNS) have been inferred as two mechanisms related to lead's neurotoxicity, and excessive reactive oxygen species (ROS) can promote oxidative stress and apoptosis facilitation. Few studies systematically investigated the potential relationship among oxidative stress, ROS generation, and apoptosis facilitation after lead exposure in earlier life as a whole. To better understand the adverse effect on the developing central nervous system (CNS) after lead exposure during pregnancy and lactation, the indexes of oxidative stress, apoptosis status, and Bax and Bcl-2 expression of offspring rats' hippocampus were determined. Pregnant rats were randomly divided into four groups and given free access to drinking water which contained 0 %, 0.05 %, 0.1 %, and 0.2 % Pb(AC)(2) respectively from gestation day 0 to postnatal day 21 (PND21). Results showed that ROS and malondialdehyde level of either PND7 or PND21 pups' hippocampus were significantly raised; reduced glutathione level and superoxide dismutase activity were obviously decreased following the increase of blood and brain lead level. Similar to apoptotic indexes, Bax/Bcl-2 ratio increased after 0.1 % and 0.2 % Pb(AC)(2) exposure, especially for the pups on PND7. Comparing with cortex, the hippocampus seemed much more sensitive to damage induced by lead. We concluded that the disruption of pro-oxidant and antioxidant balance and apoptosis facilitation could be associated with the mechanisms of neurotoxicity after lead exposure in earlier life.

  11. Metabolic and Histopathological Effects of Fructose Intake During Pregestation, Gestation and Lactation in Rats and their Offspring

    PubMed Central

    Sarı, Erkan; Yeşilkaya, Ediz; Bolat, Ahmet; Topal, Turgut; Altan, Bilal; Fidancı, Kürşat; Saldır, Mehmet; Erdem, Galip; Gülgün, Mustafa; Gülcan Kurt, Yasemin; Güven, Ahmet

    2015-01-01

    Objective: Studies have demonstrated a significant relationship between maternal fructose intake and metabolic outcome in their offspring. However, there is a paucity of data about the long-term effects of fructose intake on the offspring of fructose-fed dams. Therefore, we planned a study to evaluate the long-term effects of fructose intake on the offspring of dam rats fed a high-fructose diet. Methods: Sixteen virgin female Sprague-Dawley rats were divided into two groups. Group 1 received a regular diet and Group 2 a high-fructose diet. Both groups received their experimental diets for 8 weeks before conception. They were mated and continued to feed with their experimental diet during mating and during their pregnancy and lactation periods. After weaning, the offspring from each group were divided into two groups. Group 1A received a regular diet, Group 1B - a fructose diet, Group 2A - a regular diet and Group 2B received a fructose diet. After weaning, the offspring were anesthetized and blood samples were collected for biochemical analysis. Liver, kidney and retroperitoneal adipose tissue were harvested for histopathological examination. Primary antibodies against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined as early inflammation markers. Results: After weaning, while daily water consumption was found to be significantly higher in Groups 2B and 1B (p<0.01), daily laboratory chow consumption was significantly lower in Groups 1A and 2A (p<0.01). Body weight was significantly higher in Groups 1B and 2B (p<0.01). Serum glucose, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were found to be increased and high-density lipoprotein cholesterol levels decreased in Group 2B (p<0.05). The intensities of iNOS staining in the retroperitoneal adipose tissue, COX-2 staining in the liver and both iNOS and COX-2 staining in the kidney were higher in Group 2B (p<0.05). Conclusion

  12. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

    PubMed

    Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

    2016-03-01

    The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety.

  13. Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium.

    PubMed

    Feng, Liuxing; He, Xiao; Xiao, Haiqing; Li, Zijie; Li, Fuliang; Liu, Nianqing; Chai, Zhifang; Zhao, Yuliang; Zhang, Zhiyong

    2007-01-01

    Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.

  14. 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.

    PubMed

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

    2012-10-01

    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 μg/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

  15. Effects of number and gender of offspring on quality of life among older adults: evidence from the Korean Longitudinal Study of Aging, 2006–2012

    PubMed Central

    Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Cho, Kyung-Hee; Choi, Jae-Woo; Park, Eun-Cheol

    2015-01-01

    Objectives We examined correlations between number and gender of offspring and health-related quality of life (HRQoL) and quality of life (QoL) in older adults. Setting We used data from the 2006–2012 data sets of the Korean Longitudinal Study of Aging. Participants There were 10 242, 8680, 7907 and 7480 participants in 2006, 2008, 2010 and 2012, respectively. Interventions Number and gender of offspring. Primary and secondary outcome measures We measured participants’ QoL and HRQoL using a visual analogue scale developed by the Korea Labour Institute and which is similar to the EQ-VAS, a European measure. Results We estimated the HRQoL and QoL of individuals with offspring. Estimates for the HRQoL and QoL of parents with no offspring were −7.762 and −9.384, respectively (both p<0.0001) versus parents with two offspring. For parents with five or more offspring, the estimates for the HRQoL and QoL were −1.529 and 0.885, respectively (p<0.001 and p<0.017, respectively) compared with parents with two offspring. For fathers with no offspring compared with fathers with two offspring, the estimates for the HRQoL and QoL were −6.143 and −7.492, respectively (both p<0.0001). Conclusions These results suggest that number of offspring is associated with both HRQoL and QoL. Those with no offspring showed the lowest HRQoL and QoL. Although having five or more children had positive associations with QoL, it had negative associations with HRQoL. Public health services for those with poor quality of life should provide effective support programmes and services based on these findings. PMID:26063566

  16. Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ(9)-THC exposure.

    PubMed

    Beggiato, Sarah; Borelli, Andrea Celeste; Tomasini, Maria Cristina; Morgano, Lucia; Antonelli, Tiziana; Tanganelli, Sergio; Cuomo, Vincenzo; Ferraro, Luca

    2017-03-01

    The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta(9)-tetrahydrocannabinol (Δ(9)-THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ(9)-THC induced a significant reduction (p<0.05) in basal and K(+)-evoked [(3)H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [(3)H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ(9)-THC induced a significant reduction of CB1 receptor binding (Bmax) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ(9)-THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K(+)-evoked [(3)H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of

  17. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    EPA Pesticide Factsheets

    behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

  18. Impairment of male rat reproductive function in F1 offspring from dams exposed to 2-bromopropane during gestation and lactation.

    PubMed

    Kang, Kyung-Sun; Li, Guang-Xun; Che, Jeong-Hwan; Lee, Yong-Soon

    2002-01-01

    The toxic effects of 2-bromopropane (2-BP) on the reproductive tracts of male F1 offspring from dams exposed to 2-BP during gestation and lactation were investigated. Ten pregnant (sperm-positive) Sprague-Dawley rats per group were exposed sc to 2-BP at 135, 405, and 1215 mg/kg/day from gestation day (GD) 6 to postnatal day (PND) 20. 2-BP decreased the proportion of dams littering at the two highest doses. At the highest dose, the rate of delivery and surviving pups were significantly lower than in the controls (P < or = 0.05). The relative weights of testes vs. brain were significantly lower than the controls (P < or = 0.05) on PND 33 and 63 at 405 mg/kg/day, and on PND 90 at 1215 mg/kg/day in the F1 rats. Seminiferous tubule atrophy, germ cell loss, and increased Leydig cell proliferation were observed at the highest dose by histopathologic examination. Female offspring has a decrease in all follicle types at the high dose. These results suggest that gestational and lactational exposure to 2-BP at a high maternally toxic dose impairs the development of the reproductive organs of the offspring.

  19. Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring

    PubMed Central

    Nazari, Zahra; Nabiuni, Mohammad; Saeidi, Mohsen; Golalipour, Mohammad Jafar

    2017-01-01

    Objective(s): The link between a hyperglycemic intrauterine environment and the development of diabetes later in life has been observed in offspring exposed to gestational diabetes mellitus (GDM), but the underlying mechanisms for this phenomenon are still not clear. Reduced β-cells mass is a determinant in the development of diabetes (type 1 and type 2 diabetes). Some recent studies have provided evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring’s β-cells by disruption in the CDK4-pRB-E2F1 pathway. Materials and Methods: Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and control dams at the age of 15 week were randomly scarified and pancreases were harvested. Langerhans islets of diabetic and control groups were digested by collagenase digestion technique. After RNA extraction, we investigated the expressions of the kir 6.2 and CDK4-pRB-E2F1 pathway genes by quantitative real-time PCR. Results: GDM reduced the expression of CDK4-pRB-E2F1 pathway genes in Langerhans islets cells of offspring. CDK4, pRB and E2F1 pathway genes were downregulated in diabetic islets by 51%, 35% and 84%, respectively. Also, the expression of Kir 6.2 was significantly decreased in diabetic islets by 88%. Conclusion: We suggest that the effect of gestational diabetes on offspring’s β-cells may be primarily caused by the suppression of CDK4-pRB-E2F1 pathway. PMID:28293391

  20. Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice.

    PubMed

    Ben Slima, A; Ben Abdallah, F; Keskes-Ammar, L; Mallek, Z; El Feki, A; Gdoura, R

    2012-05-01

    Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.

  1. An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring

    PubMed Central

    Wirbisky, Sara E.; Weber, Gregory J.; Sepúlveda, Maria S.; Lin, Tsang-Long; Jannasch, Amber S.; Freeman, Jennifer L.

    2016-01-01

    The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID:26891955

  2. Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

    PubMed

    Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L

    2014-04-01

    Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges.

  3. To have and to hold: codependency as a mediator or moderator of the relationship between substance abuse in the family of origin and adult-offspring medical problems.

    PubMed

    Harkness, Daniel

    2003-01-01

    This pilot study explored the putative role of codependency as a mediator or moderator of the relationship between substance abuse in the family of origin (SAFO) and offspring medical problems in a counterbalanced multiple-treatment experiment with a heterogenous sample of adult males and females. Codependent attitude and behavior were moderators that attenuated the relationship between SAFO and two measures of acute offspring medical problems, but codependent behavior amplified the relationship between SAFO and chronic medical problems. Challenging replications are called for.

  4. "Green odor" inhalation by stressed rat dams reduces behavioral and neuroendocrine signs of prenatal stress in the offspring.

    PubMed

    Fujita, Sayaka; Ueki, Shiori; Miyoshi, Michio; Watanabe, Tatsuo

    2010-07-01

    Chronic maternal stress during pregnancy results in the "prenatally stressed" offspring displaying behavioral and neuroendocrine alterations that persist into adulthood. We investigated how inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) by stressed dams might alter certain indices of prenatal stress in their offspring. These indices were depression-like behavior (increased immobility time in the forced-swim test) and acute restraint stress-induced changes in hypothalamo-pituitary-adrenocortical (HPA) axis activity [plasma corticosterone (CORT) and ACTH levels and the number of Fos-immunoreactive cells in the hypothalamic paraventricular nucleus (an index of neuronal activity)]. Pregnant rats were exposed to restraint stress for 60 min/day for 10 days (gestational days 10-19). The prenatally stressed offspring exhibited significant increases in depression-like behavior and in restraint stress-induced ACTH, CORT, and Fos responses, unless their dam had been exposed to green odor. The behavioral effect of the odor was also seen in offspring that were fostered by unstressed dams. The results obtained in the dams themselves were as follows. In vehicle-exposed stressed dams, but not in green odor-exposed ones, total body and adrenal weights were significantly decreased or increased, respectively. Depression-like behavior was not observed in the vehicle-exposed stressed dams themselves. Green odor inhalation prevented the impairment of maternal behavior induced by restraint stress. Thus, exposure of dams to stress may affect both the fetal brain and fetal HPA axis, and also maternal behavior, leading to altered behavioral and neuroendocrine responses in the offspring. Such effects may be prevented by the stressed dams inhaling green odor.

  5. Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase.

    PubMed

    Zhu, Wei-Fen; Zhu, Jian-Fang; Liang, Li; Shen, Zheng; Wang, Ying-Min

    2016-05-01

    Small for gestational age (SGA) at birth increases the risk of developing metabolic syndrome, which encompasses various symptoms including hypertriglyceridemia. The aim of the present study was to determine whether maternal undernutrition during pregnancy may lead to alterations in hepatic triglyceride content and the gene expression levels of hepatic lipoprotein lipase (LPL) in SGA male offspring. The present study focused on the male offspring in order to prevent confounding factors, such as estrus cycle and hormone profile. Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum chow diet or 50% food restricted diet from pregnancy day 1 until parturition. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to measure the gene expression levels of hepatic LPL at day 1 and upon completion of the third week of age. Chromatin immunoprecipitation quantified the binding activity of liver X receptor‑α (LXR‑α) gene to the LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics. At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of hepatic triglycerides, which was concomitant with increased expression levels of LPL. Since LPL is regulated by LXR‑α, the expression levels of LXR‑α were detected in appropriate for gestational age and SGA male offspring. Maternal undernutrition during pregnancy led to an increase in the hepatic expression levels of LXR‑α, and enriched binding to the putative LXR response elements in the LPL promoter regions in 3‑week‑old male offspring. In addition, enhanced acetylation of histone H3 [H3 lysine (K)9 and H3K14] was detected surrounding the LPL promoter. The results of the present study indicated that maternal undernutrition during pregnancy may lead to an increase in hepatic triglycerides, via alterations in the transcriptional and epigenetic regulation of the LPL gene.

  6. The effects of exposure to titanium dioxide nanoparticles during lactation period on learning and memory of rat offspring.

    PubMed

    Mohammadipour, Abbas; Hosseini, Mahmoud; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Pourganji, Masoume; Bideskan, Alireza Ebrahimzadeh

    2016-02-01

    Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious.

  7. Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

    PubMed Central

    Han, Mei; Zhang, Ji-chun; Hashimoto, Kenji

    2017-01-01

    Objective Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA. PMID:28138113

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

    PubMed

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

    2015-02-01

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

  9. Retinoic acid exposure on gestational days 11 to 13 impairs swallowing in rat offspring.

    PubMed

    Holson, R R; Adams, J; Ferguson, S A; Scalzo, F M

    2000-01-01

    We have previously reported that exposure to 10 mg/kg of all-trans-retinoic acid (RA) daily on the 11th, 12th, and 13th days of rat gestation is lethal to all fetuses so exposed, due to an inability to suckle [R.R. Holson et al., Neurotoxicol Teratol 19 (1997) 347-353]. Because this lethal RA effect could be due to any of a variety of causes, from olfactory problems in locating the nipple to a motor problem in sucking or swallowing, we performed the following experiment. Albino dams were exposed to 10-mg/kg RA or vehicle daily over gestational days (GDs) 11 to 13. On the afternoon of GD 21 all pups were delivered by c-section. Tongue cannulae were inserted into the oral cavity of these offspring, and used to infuse a solution of condensed milk directly into the mouth. During and after each of four infusions, the behavioral response to the infusion (typically rolling and curling) was recorded. Controls responded well to this procedure, typically swallowing all milk so infused. In contrast, almost no RA-exposed neonates were able to swallow milk infused into the oral cavity. In such cases the milk simply dribbled out of the mouth, while the stomach was found to be empty at autopsy. However, the RA-treated animals did seem aware that milk was entering their mouths, because they showed a normal behavioral response to milk infusion. We conclude that GD 11-13 retinoid lethality is due to motor not sensory problems in the control of swallowing.

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

    PubMed

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

    2011-04-01

    Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.4±0.8 and 3.8±0.3 sessions, respectively, p<0.05). Performance in fixed ratio-5 conditioning showed the RR (5.4±1.1), CR (4.0±0.8), and RC (5.0±0.8) offspring required more sessions to reach performance criterion than CC offspring (2.5±0.5, p<0.05). Furthermore, motivational effects during the progressive ratio test revealed less responding in the RR (48.1±17), CR (74.7±8.4), and RC (65.9±11.2) for positive reinforcement vs. the CC offspring (131.5±7.5, p<0.05). These findings demonstrate negative developmental programming effects due to perinatal isocaloric low protein diet on learning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior.

  11. Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.

    PubMed

    Bonomo, Isabela Teixeira; Lisboa, Patrícia Cristina; Passos, Magna Cottini Fonseca; Alves, Simone Bezerra; Reis, Adelina Martha; de Moura, Egberto Gaspar

    2008-08-01

    Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum tri-iodothyronine (T(3)). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO - injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C - control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with (125)I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (-51%), T(3) (-23%), and thyroxine (-21%), lower thyroid (125)I uptake (-41%), liver mGPD (-55%), and pituitary D2 (-51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

  12. Birth outcomes among offspring of adult cancer survivors: a population-based study.

    PubMed

    Stensheim, Hanne; Klungsøyr, Kari; Skjaerven, Rolv; Grotmol, Tom; Fosså, Sophie D

    2013-12-01

    Do cancer and cancer treatment influence patients' subsequent pregnancies and outcomes for the offspring? In this study, we compared birth outcomes in 3,915 female and male survivors and 144,653 controls from the general population with similar parity, by merging data from the Cancer Registry and the Medical Birth Registry of Norway. The cancer survivors were diagnosed at age 16-45 in the period 1967-2004. Subgroups of nulliparous survivors (childless before cancer) and primiparous (one pregnancy before and one after cancer) were analyzed, using logistic regression to compare birth outcomes with controls, focusing perinatal death, congenital anomalies, preterm birth (<37 gestational weeks) and low birth weight (LBW, <2,500 g). We adjusted for maternal age, birth period and educational level. Nulliparous female survivors' offspring had increased risk of preterm birth (OR = 1.30 [95% CI 1.05-1.61]) but similar risks of LBW and perinatal death as their controls. Primiparous female survivors differed from their controls, with higher frequency of preterm birth (OR = 1.89 [95% CI 1.40-2.56]) and LBW at term (OR = 2.02 [95% CI 1.15-3.55]). A borderline significant increase of perinatal death was seen among offspring of primiparous female survivors, with OR = 1.92 (95% CI 0.98-3.76). Offspring of male survivors did not differ from their controls. For all cancer types combined, no increased risk of congenital anomalies was seen among either female or male survivors' offspring. Pregnant female cancer survivors should be offered close follow-up, as there is an increased risk of adverse birth outcomes, in particular among those with higher parities.

  13. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study

    PubMed Central

    Al-Gholam, Marwa A.; El-Mehi, Abeer E.; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-01-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord. PMID:27051566

  14. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study.

    PubMed

    Al-Gholam, Marwa A; Nooh, Hanaa Zakaria; El-Mehi, Abeer E; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-03-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord.

  15. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    PubMed

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-10-29

    Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain. Furthermore, the level of brain-derived neurotrophic factor (BDNF) was analyzed. Pregnant female Wistar rats received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring, while the control animals received drinking water. During the feeding of pups, mothers from the Pb-group were continuously receiving PbAc. Pups of both groups were weaned at postnatal day 21 and then until postnatal day 28 received only drinking water. 28-Day old pups were sacrificed and the ultrastructural changes as well as expression of presynaptic (VAMP1/2, synaptophysin, synaptotagmin-1, SNAP25, syntaxin-1) and postsynaptic (PSD-95) proteins were analyzed in: forebrain cortex, cerebellum and hippocampus. Our data revealed that pre- and neonatal exposure to low dose of Pb promotes pathological changes in synapses, including nerve endings swelling, blurred and thickened synaptic cleft structure as well as enhanced density of synaptic vesicles in the presynaptic area. Moreover, synaptic mitochondria were elongated, swollen or shrunken in Pb-treated animals. These structural abnormalities were accompanied by decrease in the level of key synaptic proteins: synaptotagmin-1 in cerebellum, SNAP25 in hippocampus and syntaxin-1 in cerebellum and hippocampus. In turn, increased level of synaptophysin was

  16. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    PubMed

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-12-12

    Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain. Furthermore, the level of brain-derived neurotrophic factor (BDNF) was analyzed. Pregnant female Wistar rats received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring, while the control animals received drinking water. During the feeding of pups, mothers from the Pb-group were continuously receiving PbAc. Pups of both groups were weaned at postnatal day 21 and then until postnatal day 28 received only drinking water. 28-day old pups were sacrificed and the ultrastructural changes as well as expression of presynaptic (VAMP1/2, synaptophysin, synaptotagmin-1, SNAP25, syntaxin-1) and postsynaptic (PSD-95) proteins were analyzed in: forebrain cortex, cerebellum and hippocampus. Our data revealed that pre- and neonatal exposure to low dose of Pb promotes pathological changes in synapses, including nerve endings swelling, blurred and thickened synaptic cleft structure as well as enhanced density of synaptic vesicles in the presynaptic area. Moreover, synaptic mitochondria were elongated, swollen or shrunken in Pb-treated animals. These structural abnormalities were accompanied by decrease in the level of key synaptic proteins: synaptotagmin-1 in cerebellum, SNAP25 in hippocampus and syntaxin-1 in cerebellum and hippocampus. In turn, increased level of synaptophysin was

  17. Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Thamotharan, Shanthie; Shin, Bo-Chul; Stout, David; Devaskar, Sherin U

    2012-06-01

    Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype.

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

    PubMed

    Lomanowska, Anna M; Melo, Angel I

    2016-01-01

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

  19. Evaluation of a group intervention to assist aging parents with permanency planning for an adult offspring with special needs.

    PubMed

    Botsford, Anne L; Rule, David

    2004-07-01

    More than three-fourths of older adults with developmental disabilities and mental illness live in the community with aging parents, the majority of whom do not complete plans for the residential, financial, and legal future of their offspring. The authors used a true experimental design to evaluate the effectiveness of a six-week psychoeducational group intervention with 27 older mothers. Data collected in pre- and posttest telephone interviews were analyzed with repeated measures MANCOVA to test five hypotheses. Significant multivariate effects were found for mothers' knowledge and awareness about permanency planning, confidence and competence to plan, planning activities, and stage of planning. Findings support use of group interventions with older parents and underscore the need for professional education about planning for adults with special needs.

  20. Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring.

    PubMed

    Wu, Ling-Yi; Chen, Jain-Fang; Tao, Pao-Luh; Huang, Eagle Yi-Kung

    2009-11-25

    Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction) in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p.) in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.

  1. Tobacco Smoking: Patterns, Health Consequences for Adults, and the Long-term Health of the Offspring

    PubMed Central

    Maritz, Gert S.; Mutemwa, Muyunda

    2012-01-01

    Tobacco use started several centuries ago and increased markedly after the invention of the cigarette making machine. Once people start smoking they find it difficult to quit the habit. This is due to the addictive effect of nicotine in tobacco smoke. Various epidemiologic and laboratory studies clearly showed that smoking is associated with various diseases such as heart diseases, asthma and emphysema and the associated increase in morbidity and mortality of smokers. Several studies implicate nicotine as the causative factor in tobacco smoke. Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in an increase in the incidence of cancer in smokers. While the smoking habit is decreasing in developed countries, tobacco use increases in the developing countries. Smoking prevalence is also highest in poor communities and amongst those with low education levels. It is important to note that, although ther is a decline in the number of smokers in the developed countries, there is a three to four decades lag between the peak in smoking prevalence and the subsequent peak in smoking related mortality. It has been shown that maternal smoking induces respiratory diseases in the offspring. There is also evidence that parental smoking may program the offspring to develop certain diseases later in life. Various studies showed that maternal nicotine exposure during pregnancy and lactation via tobacco smoke of nicotine replacement therapy (NRT), program the offspring to develop compromised lung structure later in life with the consequent compromised lung function. This implies that NRT is not an option to assist pregnant or lactating smokers to quit the habit. Even paternal smoking may have an adverse effect on the health of the offspring since it has been shown that 2nd and 3rd hand smoking have adverse health consequences for those exposed to it. PMID:22980343

  2. Maternal psychological stress-induced developmental disability, neonatal mortality and stillbirth in the offspring of Wistar albino rats

    PubMed Central

    Govindaraj, Sakthivel; Shanmuganathan, Annadurai; Rajan, Ravindran

    2017-01-01

    Background Stress is an inevitable part of life, and maternal stress during the gestational period has dramatic effects in the early programming of the physiology and behavior of offspring. The developmental period is crucial for the well-being of the offspring. Prenatal stress influences the developmental outcomes of the fetus, in part because the developing brain is particularly vulnerable to stress. The etiology of birth defects of the offspring is reported to be 30–40% genetic and 7–10% multifactorial, with the remaining 50% still unknown and also there is no clear cause for neonatal mortality and still-birth. Objective The present study explores the association of maternal psychological stress on mother and the offspring’s incidence of birth defects, stillbirth, and neonatal mortality. Study design Pregnant animals were restrained to induce psychological stress (3 times per day, 45 minutes per session). Except control group, other animals were exposed to restraint stress during the gestational period: early gestational stress (EGS, stress exposure during 1st day to 10th days of gestational period), late gestational stress (LGS, stress exposure during 11th day to till parturition), and full term gestational stress (FGS, stress exposure to the whole gestational period). The effects of maternal stress on the mother and their offspring were analyzed. Results Expectant female rats exposed to stress by physical restraint showed decreased body weight gain, food intake, and fecal pellet levels. Specifically, the offspring of female rats subjected to late gestational and full term gestational restraint stress showed more deleterious effects, such as physical impairment (LGS 24.44%, FGS 10%), neonatal mortality (EGS 2.56%, LGS 24.44%, FGS 17.5%), stillbirths (FGS 27.5%), low birth weight (EGS 5.42g, LGS 4.40g, FGS 4.12g), preterm births (EGS 539 Hrs, LGS 514 Hrs, FGS 520.6 Hrs), and delayed eyelid opening (EGS 15.16 Days, LGS 17 Days, FGS 17.67 Days). Conclusion

  3. Nephrotoxic effects on offspring of rats chronically treated with mercuric chloride

    SciTech Connect

    Rusk, T.L.

    1983-08-01

    Repeated subcutaneous injections of HgCl/sub 2/ at a dose of either 4.0 or 2.0 mg/kg produced toxic effects in rats when administered during the last 9 days of gestation. Females exhibited diarrhea, anorexia and weight loss of varying severity. Maternal renal function was monitored by urinalysis and was shown to be impaired during the early days of treatment but returned to normal later. Histological evaluation of adult kidneys after 2 days of treatment demonstrated the nephrotoxic effects of HgCl/sub 2/. Evidence of the regenerative process was found in tubules lined with densely packed, flattened cuboidal epithelial cells. Pup birth weight among HgCl/sub 2/-exposed litters was significantly lower than that of control litters. Nephrotoxic effects were not identifiable in pups though the presence of mercury was confirmed in fetal kidneys. 93 refs., 7 figs., 3 tabs.

  4. Early maternal care predicts reliance on social learning about food in adult rats.

    PubMed

    Lindeyer, Charlotte M; Meaney, Michael J; Reader, Simon M

    2013-03-01

    Many vertebrates rely extensively on social information, but the value of information produced by other individuals will vary across contexts and habitats. Social learning may thus be optimized by the use of developmental or current cues to determine its likely value. Here, we show that a developmental cue, early maternal care, correlates with social learning propensities in adult rodents. The maternal behavior of rats Rattus norvegicus with their litters was scored over the first 6 days postpartum. Rat dams show consistent individual differences in the rate they lick and groom (LG) pups, allowing them to be categorized as high, low, or mid-LG mothers. The 100-day old male offspring of high and low-LG mothers were given the opportunity to learn food preferences for novel diets from conspecifics that had previously eaten these diets ("demonstrators"). Offspring of high-LG mothers socially learned food preferences, but offspring of low-LG mothers did not. We administered oxytocin to subjects to address the hypothesis that it would increase the propensity for social learning, but there were no detectable effects. Our data raise the possibility that social learning propensities may be both relatively stable throughout life and part of a suite of traits "adaptively programmed" by early developmental experiences.

  5. Chronic Maternal Vitamin B12 Restriction Induced Changes in Body Composition & Glucose Metabolism in the Wistar Rat Offspring Are Partly Correctable by Rehabilitation

    PubMed Central

    Kumar, Kalle Anand; Lalitha, Anumula; Reddy, Umakar; Chandak, Giriraj Ratan; Sengupta, Shantanu; Raghunath, Manchala

    2014-01-01

    Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers from conception or parturition and their offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with control males. Six each of pregnant B12R dams were rehabilitated from conception and parturition and their offspring weaned to control diet. While offspring of six B12R dams were weaned to control diet, those of the remaining six B12R dams continued on B12R diet. Biochemical parameters and body composition were determined in dams before mating and in male offspring at 3, 6, 9 and 12 months of their age. Dietary vitamin B12 restriction increased body weight but decreased LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams. Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%, basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12 months age, B12R offspring had higher (than controls) fasting plasma glucose, insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic enzyme activities were increased. B12R offspring had increased oxidative stress and decreased antioxidant status. Changes in body composition, glucose metabolism and stress were reversed by rehabilitating B12R dams from conception, whereas rehabilitation from parturition and weaning corrected them partially, highlighting the importance of vitamin B12 during pregnancy and lactation on growth, muscle development, glucose tolerance and metabolism in the offspring. PMID:25398136

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

    PubMed

    Kumar, Kalle Anand; Lalitha, Anumula; Reddy, Umakar; Chandak, Giriraj Ratan; Sengupta, Shantanu; Raghunath, Manchala

    2014-01-01

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

  7. The consequences of prenatal and/or postnatal methamphetamine exposure on neonatal development and behaviour in rat offspring.

    PubMed

    McDonnell-Dowling, Kate; Kelly, John P

    2015-12-01

    Methamphetamine (MA) has become a popular drug of abuse in recent years not only in the general population but also amongst pregnant women. Although there is a growing body of preclinical investigations of MA exposure during pregnancy, there has been little investigation of the consequences of such exposure via the breast milk during the neonatal period. Therefore, the aim of this study was to determine the consequences of MA exposure during pregnancy and lactation on neurodevelopment and behaviour in the rat offspring. Pregnant Sprague-Dawley dams received MA (3.75 mg/kg) or control (distilled water) once daily via oral gavage from gestation day 7-21, postnatal day 1-21 or gestation day 7- postnatal day 21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. Prenatal MA significantly reduced maternal weight gain, with a concomitant reduction in food intake. A significant increase in neonatal pup mortality was observed, being most marked in the prenatal/postnatal MA group. Significant impairments in neurodevelopmental parameters were also evident in all MA treatment groups including somatic development (e.g. pinna unfolding, fur appearance, eye opening) and behavioural development (e.g. surface righting, inclined plane test, forelimb grip). In conclusion, this study demonstrates that exposure to MA during any of these exposure periods (prenatal and/or postnatal) can have a profound effect on neonatal outcome, suggesting that regardless of the exposure period MA is associated with detrimental consequences in the offspring. These results indicate that in the clinical scenario, exposure during lactation needs to be considered when assessing the potential harmful effects of MA on offspring development.

  8. Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

    PubMed

    Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

    2015-11-01

    Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

  9. Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring.

    PubMed

    Kim, Ki Chan; Lee, Dong-Keun; Go, Hyo Sang; Kim, Pitna; Choi, Chang Soon; Kim, Ji-Woon; Jeon, Se Jin; Song, Mi-Ryoung; Shin, Chan Young

    2014-02-01

    Imbalance in excitatory/inhibitory signal in the brain has been proposed as one of the main pathological features in autism spectrum disorders, although the underlying cellular and molecular mechanism is unclear yet. Because excitatory/inhibitory imbalance can be induced by aberration in glutamatergic/GABAergic neuronal differentiation, we investigated the mechanism of dysregulated neuronal differentiation between excitatory and inhibitory neurons in the embryonic and postnatal brain of prenatally valproic acid-exposed rat offspring, which is often used as an animal model of autism spectrum disorders. Transcription factor Pax6, implicated in glutamatergic neuronal differentiation, was transiently increased in embryonic cortex by valproate exposure, which resulted in the increased expression of glutamatergic proteins in postnatal brain of offspring. Chromatin immunoprecipitation showed increased acetylated histone binding on Pax6 promoter region, which may underlie the transcriptional up-regulation of Pax6. Other histone deacetylase (HDAC) inhibitors including TSA and SB but not valpromide, which is devoid of HDAC inhibitor activity, induced Pax6 up-regulation. Silencing Pax6 expression in cultured rat primary neural progenitor cells demonstrated that up-regulation of Pax6 plays an essential role in valproate-induced glutamatergic differentiation. Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with MPEP treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed offspring. Together, environmental factors may contribute to the imbalance in excitatory/inhibitory neuronal activity in autistic brain by altering expression of transcription factors governing glutamatergic/GABAergic differentiation during fetal neural development, in conjunction with the genetic preload.

  10. Life-cycle exposure to BDE-47 results in thyroid endocrine disruption to adults and offsprings of zebrafish (Danio rerio).

    PubMed

    Zhao, Xuesong; Ren, Xin; Ren, Baixiang; Luo, Zhouying; Zhu, Rong

    2016-12-01

    2,2,4',4'-Tetrabromodi-phenyl ether (BDE-47) is predominantly concentrated in humans and wildlife and disturbs thyroid hormone homeostasis. The purpose of this study was to characterize the thyroid endocrine disruption induced by life-cycle exposure to BDE-47 in adults and offspring of zebrafish (Danio rerio). We exposed zebrafish embryos at the blastula stage to different concentrations of BDE-47 (1, 5, and 10μg/L). Exposure duration was 180days until fish reached adulthood. In F0 larvae, exposure decreased survival and increased malformations at 4 dpf. Thyroid hormone concentrations did not differ significantly between the F0 larvae and controls. All exposures significantly up-regulated expression of tshß, pa8, ugt1 and tg and down-regulated ttr. Significant up-regulation of dio2 and crh was observed in the 10μg/L BDE-47 group. There was no significant difference in the growth and somatic index between F0 adults and controls. BDE-47 (10μg/L) significantly decreased whole-body content of thyroxine (T4) but significantly increased triiodothyronine (T3) in both sexes. All exposures up-regulated expression of crh, tshß, pa8, ugt1 and tg and down-regulated ttr. Exposure to 10μg/L BDE-47 significantly up-regulated dio2 and ugt1 in both sexes. BDE-47 exposure (5 and 10μg/L) significantly increased the activity of pethoxy-resorufin-O-deethylase and UDP-glucuronosyl transferase. BDE-47 (10μg/L) significantly increased activity of ethoxy- and methoxy-resorufin-O-deethylase. In F1 offspring without continued BDE-47 (10μg/L) treatment, T4 significantly decreased and T3 increased. T4 was further decreased and T3 was further increased with continued BDE-47 treatment. Continued BDE-47 exposure decreased hatching and increased malformation compared with those without BDE-47 exposure. Expression of crh, tshß, dio2, pa8, ugt1 and tg was significantly up-regulated without BDE-47 exposure and with continued exposure. With continued BDE-47 exposure, dio1 was significantly

  11. Ultra high frequency-electromagnetic field irradiation during pregnancy leads to an increase in erythrocytes micronuclei incidence in rat offspring.

    PubMed

    Ferreira, Amâncio Romanelli; Knakievicz, Tanise; Pasquali, Matheus Augusto de Bittencourt; Gelain, Daniel Pens; Dal-Pizzol, Felipe; Fernández, Claudio Enrique Rodriguez; de Salles, Alvaro Augusto de Almeida; Ferreira, Henrique Bunselmeyer; Moreira, José Cláudio Fonseca

    2006-12-03

    Mobile telephones and their base stations are an important ultra high frequency-electromagnetic field (UHF-EMF) source and their utilization is increasing all over the world. Epidemiological studies suggested that low energy UHF-EMF emitted from a cellular telephone may cause biological effects, such as DNA damage and changes on oxidative metabolism. An in vivo mammalian cytogenetic test, the micronucleus (MN) assay, was used to investigate the occurrence of chromosomal damage in erythrocytes from rat offspring exposed to a non-thermal UHF-EMF from a cellular phone during their embryogenesis; the irradiated group showed a significant increase in MN occurrence. In order to investigate if UHF-EMF could also alter oxidative parameters in the peripheral blood and in the liver - an important hematopoietic tissue in rat embryos and newborns - we also measured the activity of antioxidant enzymes, quantified total sulfhydryl content, protein carbonyl groups, thiobarbituric acid-reactive species and total non-enzymatic antioxidant defense. No significant differences were found in any oxidative parameter of offspring blood and liver. The average number of pups in each litter has also not been significantly altered. Our results suggest that, under our experimental conditions, UHF-EMF is able to induce a genotoxic response in hematopoietic tissue during the embryogenesis through an unknown mechanism.

  12. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    PubMed

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  13. Mechanism of the delayed puberty onset in offspring of rats that consumed aqueous extract of Hibiscus sabdariffa during pregnancy.

    PubMed

    Iyare, E E; Adegoke, O A

    2008-01-01

    Consumption of extracts of Hibiscus sabdariffa (family: malvaceae) during pregnancy has been shown to cause maternal malnutrition which has been linked to various adverse conditions like increased postnatal weight gain, delayed puberty onset and elevated body weight and body mass index at onset of puberty in the female offspring. The present study was designed to investigate the possible mechanism underlying this. Eighteen in-bred pregnant Sprague-Dawley rats were on day 1 of pregnancy, randomly divided into three groups of six animals each. Group A (control) was given tap water to drink. Group B was given 0.6g extract/100ml while Group C was given 1.8g extract/100ml as their drinking solution. All groups received normal rat chow and their drinking solution ad libitum. Fluid and food intake and dam weights were measured daily throughout pregnancy. On gestational day 18, blood sample was withdrawn from each rat for estimation of plasma Na ion and corticosterone levels. On the day of delivery, the solutions of the extracts of Hibiscus sabdariffa were withdrawn and replaced with tap water. After 21 days, the pups were weaned to tap water and food ad libitum. Pups weight and age and body mass index at onset of puberty were measured. The results of the present study showed that the increased postnatal weight gain, delayed puberty onset and elevated body mass index at onset of puberty in the offspring of rats that consumed HS during pregnancy was associated with elevated maternal plasma Na ion and corticosterone levels during pregnancy.

  14. Transmission of cultural values among Mexican-origin parents and their adolescent and emerging adult offspring.

    PubMed

    Perez-Brena, Norma J; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

    2015-06-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths' adjustment and family dynamics. The current study examined the reciprocal associations in parents' and two offspring's cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers' values were associated with increases in youths' values 5 years later. In contrast, youths' familism values were associated with increases in fathers' familism values 5 years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support is crucial.

  15. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    PubMed

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

  16. Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes.

    PubMed

    Correia-Santos, André Manoel; Vicente, Gabriela C; Suzuki, Akemi; Pereira, Aline D; dos Anjos, Juliana S; Lenzi-Almeida, Kátia C; Boaventura, Gilson T

    2015-04-01

    Nutritional recommendations have promoted the increased need to consume n-3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n-3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high-fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HG); flaxseed oil group (FOG); and control group (CG) (non-diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β-cell mass in female offspring.

  17. Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning.

    PubMed

    Nobre, Jessica Lopes; Lisboa, Patricia Cristina; Lima, Natália da Silva; Franco, Juliana Gastão; Nogueira Neto, José Firmino; de Moura, Egberto Gaspar; de Oliveira, Elaine

    2012-04-01

    It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D₃ (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.

  18. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  19. Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation

    PubMed Central

    Han, Mei; Zhang, Ji-chun; Yao, Wei; Yang, Chun; Ishima, Tamaki; Ren, Qian; Ma, Min; Dong, Chao; Huang, Xu-Feng; Hashimoto, Kenji

    2016-01-01

    Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus. Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice. These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia. PMID:27824119

  20. Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring.

    PubMed

    Roy, Suchitra; Kale, Anvita; Dangat, Kamini; Sable, Pratiksha; Kulkarni, Asmita; Joshi, Sadhana

    2012-01-01

    Altered maternal micronutrients (folic acid, vitamin B(12)) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B(12) and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B(12)) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B(12). Both the vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B(12) deficient diet) increases (p<0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p<0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p<0.05) the levels of brain DHA in both the vitamin B(12) deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.

  1. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

    PubMed Central

    Zhang, Ke; Rasmussen, Dane; Wang, Junpeng; Wu, Dayong; Roemmich, James N.; Bundy, Amy; Johnson, W. Thomas; Claycombe, Kate

    2017-01-01

    Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein) diet followed by a postnatal high fat energy diet (HE, 45% fat) or low fat normal energy diet (NE, 10% fat) for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP) fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6. PMID:28141871

  2. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring.

    PubMed

    Xie, Linglin; Zhang, Ke; Rasmussen, Dane; Wang, Junpeng; Wu, Dayong; Roemmich, James N; Bundy, Amy; Johnson, W Thomas; Claycombe, Kate

    2017-01-01

    Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein) diet followed by a postnatal high fat energy diet (HE, 45% fat) or low fat normal energy diet (NE, 10% fat) for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP) fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6.

  3. Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.

    PubMed

    Banji, David; Banji, Otilia J F; Pratusha, N Gouri; Annamalai, A R

    2013-09-01

    The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats. The total antioxidant activity, phycocyanins, and β carotene content were quantified in Spirulina. Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15. Treatment groups included control, Spirulina alone, sodium fluoride (20 mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500 mg/kg). Serum fluoride levels were determined on ED 20 and PND 11. Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum. Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress. Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells. Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring.

  4. Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.

    PubMed

    Zhu, Yu-Peng; Xi, Shu-Hua; Li, Ming-Yan; Ding, Ting-Ting; Liu, Nan; Cao, Fu-Yuan; Zeng, Yang; Liu, Xiao-Jing; Tong, Jun-Wang; Jiang, Shou-Fang

    2017-03-01

    Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data

  5. Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

    PubMed

    Zhong, Liang; Luo, Foquan; Zhao, Weilu; Feng, Yunlin; Wu, Liuqin; Lin, Jiamei; Liu, Tianyin; Wang, Shengqiang; You, Xuexue; Zhang, Wei

    2016-10-01

    The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure.

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

    PubMed

    Sanchez-Hernandez, Diana; Poon, Abraham N; Kubant, Ruslan; Kim, Hwanki; Huot, Pedro S P; Cho, Clara E; Pannia, Emanuela; Pausova, Zdenka; Anderson, G Harvey

    2015-04-01

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

  7. Exposure to nicotine increases dopamine receptor content in the mesocorticolimbic pathway of rat dams and offspring during lactation.

    PubMed

    Pinheiro, C R; Oliveira, E; Manhães, A C; Fraga, M C; Claudio-Neto, S; Younes-Rapozo, V; Lotufo, B M; Moura, E G; Lisboa, P C

    2015-09-01

    Nicotine exposure causes the release of dopamine from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal exposure to nicotine during lactation causes hyperleptinemia in dams and pups, and leptin is known to decrease dopamine release from the VTA. Here we evaluated whether maternal exposure to nicotine during lactation causes changes in dopamine and leptin signaling pathways at the end of exposure and after 5days of withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R, D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3 contents in ARC. On PN15, NIC offspring had higher D1R, D2R and lower DAT contents in NAc, while on PN21, they had lower DAT in DS, and lower pSTAT3 content in ARC. We evidenced that postnatal nicotine exposure induces relevant changes in the brain reward system of dams and pups, possibly associated with changes in leptinemia and increased offspring anxiety-like behavior.

  8. Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

    PubMed

    Stolakis, Vasileios; Liapi, Charis; Zarros, Apostolos; Kalopita, Konstantina; Memtsas, Vassilios; Botis, John; Tsagianni, Anastasia; Kimpizi, Despoina; Varatsos, Alexios; Tsakiris, Stylianos

    2015-12-01

    The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology.

  9. PRENATAL EXPOSURE TO THE FUNGICIDE PROCHLORAZ ALTERS THE ONSET OF PARTURITION IN THE DAM AND SEXUAL DIFFERENTIATION IN MALE RAT OFFSPRING

    EPA Science Inventory

    Prenatal Exposure to the Fungicide Prochloraz alters the onset of Parturition in
    the Dam and Sexual Differentiation in Male Rat Offspring.
    N. Noriega1; E. Gray1; J. Ostby1; C. Lambright1; V. Wilson1
    1. RTD, NHEERL, ORD, USEPA, RTP, NC, USA;

    Prochloraz...

  10. Cardiac Cytochrome c Oxidase Activity and Contents of Submits 1 and 4 are Altered in Offspring by Low Prenatal Intake by Rat Dams

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial- and nuclear-subunit content after postnatal day...

  11. Prenatal low protein and postnatal high fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal low protein diets during prenatal development contribute to the development of obesity and insulin resistance in offspring. In this study, obese-prone Sprague -Dawley rats were fed diets having either 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and...

  12. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-12-14

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

  13. Young adult donor bone marrow infusions into female mice postpone age-related reproductive failure and improve offspring survival.

    PubMed

    Selesniemi, Kaisa; Lee, Ho-Joon; Niikura, Teruko; Tilly, Jonathan L

    2008-11-14

    The female reproductive axis is the first major organ system of the body to fail with advancing age. In addition to a permanent cessation of fertile potential, the loss of cyclic ovarian function in humans heralds the onset of menopause, which in turn underlies the emergence of a diverse spectrum of health issues in aging women. Recently, it was reported that bone marrow (BM) transplantation (BMT) into adult female mice conditioned a week earlier with highly cytotoxic drugs rescues ovarian function and fertility. Herein we show in mice receiving no prior conditioning regimen that once-monthly infusions of BM-derived cells retrieved from young adult female donors bearing an enhanced green fluorescent protein (EGFP) transgene sustain the fertile potential of aging wild-type females long past their time of normal reproductive senescence. The fertility-promoting effects of female donor BM are observed regardless whether the infusions are initiated in young adult or middle-aged females. Although the mechanism by which BM infusions benefit the reproductive performance of aging females remains to be elucidated, the absence of EGFP-expressing offspring suggests that it does not depend on development of mature eggs derived from germline-committed cells in the donor marrow. However, donor BM-derived somatic cells accumulate in the recipients, indicating efficient donor cell engraftment without prior conditioning. These findings provide a strong impetus to further explore development of adult stem cell-based technologies to safely extend function of the female reproductive axis into advanced age without the need for toxic pre-conditioning protocols routinely used in other models of stem cell delivery.

  14. Maternal High-Fat Diet during Pregnancy and Lactation Influences Obestatin and Ghrelin Concentrations in Milk and Plasma of Wistar Rat Dams and Their Offspring.

    PubMed

    Słupecka, Monika; Romanowicz, Katarzyna; Woliński, Jarosław

    2016-01-01

    The study aims to establish the effect of a maternal high-fat diet on obestatin concentration, total ghrelin, and ghrelin/obestatin ratio during pregnancy and lactation of Wistar rats and their offspring in the first 21 days of life. On the mating day, females were randomly allocated and fed either a high-fat diet (30% of fat; HF) or breeding diet (5% fat; BD) till the 21st day of lactation. Hormones were analyzed in the blood plasma and milk of rat dams as well as in the blood plasma of their offspring. HF resulted in a significant decrease in obestatin level on the 14th day of lactation and elevation on the 21st day. Plasma obestatin in HFD offspring was significantly higher than in BD ones. HF diet did not significantly affect dam plasma ghrelin until the 21st day of lactation. The ghrelin concentrations in milk after both diets were significantly lower than in blood plasma. Milk ghrelin in HF dams was significantly higher than in the BD ones. Plasma ghrelin from HF offspring was significantly higher than that from BD dams. Our results demonstrate that a maternal HF diet during pregnancy and lactation influences ghrelin and obestatin level in both dams and their offspring.

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

    PubMed

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

    2007-10-01

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

  16. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

    PubMed Central

    Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

  17. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring.

    PubMed

    Bueno-Vargas, Pilar; Manzano, Manuel; Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo; López-Pedrosa, Jose María

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength.

  18. Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study

    PubMed Central

    Pletcher, Mark J.; Vittinghoff, Eric; Thanataveerat, Anusorn; Bibbins-Domingo, Kirsten

    2016-01-01

    Background It is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life. Methods and Findings We used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20–39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8–5.7) for DBP = 71–80, 2.6 (0.9–7.2) for DBP = 81–90, and 3.6 (1.2–11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9–2.6) for LDL = 101–130, 2.2 (1.2–4.0) for LDL = 131–160, and 2.4 (1.2–4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors. Conclusions Using a mixed modeling approach to estimation of young adult exposures

  19. Transmission of Cultural Values among Mexican American Parents and their Adolescent and Emerging Adult Offspring

    PubMed Central

    Perez-Brena, Norma J.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.

    2015-01-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths’ adjustment and family dynamics. The current study examined the reciprocal associations in parents’ and two offspring’s cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers’ values were associated with increases in youths’ values five years later. In contrast, youths’ familism values were associated with increases in fathers’ familism values five years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant-status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support are crucial. PMID:25470657

  20. Effects of n-butylparaben on steroidogenesis and spermatogenesis through changed E₂ levels in male rat offspring.

    PubMed

    Zhang, Linyuan; Dong, Li; Ding, Sijin; Qiao, Peihuan; Wang, Chong; Zhang, Ming; Zhang, Lixia; Du, Qingcheng; Li, Yimin; Tang, Ning; Chang, Bing

    2014-03-01

    Parabens are widely used as antibacterial agents, which are concerned recently in the relationship between the use of parabens and reproductive toxicity. So that reassessment of the risk of parabens is needed. In this study, one of parabens, n-butylparaben (n-BP) was orally administered to pregnant Wistar rats (0, 64, 160, 400 and 1000 mg/kg/day) from gestation day (GD) 7 through postnatal day (PND) 21. Reduced anogenital distance (AGD) and delayed preputial separation (PPS) were observed in the male offspring. The weights of the testes were significantly reduced at PND 21-90. The weights of the epididymides were significantly reduced at all monitoring points, except PND 35. Seminal vesicle weights were significantly reduced on PND 21. Serum testosterone (T) was significantly decreased, especially on PND 49. The levels of 17β-estradiol (E2) showed an increase at each of the tested points except on PND 180. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels in the n-BP treated groups were lower on PND 21, 35 and 49 but elevated on PND 90 compared to control levels. n-BP reduced epididymal cauda sperm counts and daily sperm production in a dose-dependent manner; this difference was statistically significant at exposure groups of 400 and 1000 mg/kg/day. The present study strongly suggests that exposure to n-BP in utero and during lactation has adverse effects on the reproductive system in male offspring, with a no observed adverse effect level (NOAEL) of 160 mg/kg/day. To our knowledge, this is the first study that reports increased E2 levels of male rats following n-BP exposure; we suggest that E2 levels may be considered as biomarkers for some endocrine disrupting chemicals (EDCs).

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

    PubMed

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

    2015-02-01

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

  2. N-hexane inhalation during pregnancy alters DNA promoter methylation in the ovarian granulosa cells of rat offspring.

    PubMed

    Li, Hong; Liu, Jin; Sun, Yan; Wang, Wenxiang; Weng, Shaozheng; Xiao, Shihua; Huang, Huiling; Zhang, Wenchang

    2014-08-01

    The N-hexane-induced impact on the reproductive system of the offspring of animals exposed to n-hexane has caused great concern. Pregnant Wistar rats inhaled 500, 2 500 or 12 500 ppm n-hexane during gestational days 1-20. Clinical characteristics and developmental indices were observed. Ovarian granulosa cells were extracted from F1 rats, the number of follicles was determined in ovarian slices and promoter methylation was assessed using MeDIP-Chip. Several methods were used to analyze the scanned genes, including the Gene Ontology Consortium tools, the DAVID Functional Annotation Clustering Tool, hierarchical clustering and KEGG pathway analysis. The results indicated that the live pups/litter ratio was significantly lowest in the 12 500 ppm group. A significant decrease in secondary follicles and an increase in atresic follicles were observed in the 12 500 ppm group. The number of shared demethylated genes was higher than that of the methylated genes, and the differentially methylated genes were enriched in cell death and apoptosis, cell growth and hormone regulation. The methylation profiles of the offspring from the 500 ppm and control groups were different from those of the 2500 and 12 500 ppm groups. Furthermore, the methylation status of genes in the PI3K-Akt and NF-kappa B signaling pathways was changed after n-hexane exposure. The Cyp11a1, Cyp17a1, Hsd3b1, Cyp1a1 and Srd5a1 promoters were hypermethylated in the n-hexane-exposed groups. These results indicate that the developmental toxicity of n-hexane in F1 ovaries is accompanied by the altered methylation of promoters of genes associated with apoptotic processes and steroid hormone biosynthesis.

  3. Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring.

    PubMed

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

    2008-01-01

    The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e., antibiotic treatment or Escherichia coli exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics 3 days before parturition or live nonpathogenic E. coli Culture Collection of University of Göteborg, Sweden type strain (CCUG 29300(T)) 1 wk before parturition and up to 14 days of lactation in the drinking water. Cecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels, and intestinal inflammation were studied in 2-wk-old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae, which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability, and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300(T), also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth compared with the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen, and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of cecal Enterobacteriaceae, appears to have lasting effects on the postnatal microflora, which affects gut growth and function.

  4. Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring

    PubMed Central

    Lykkedegn, Sine; Sorensen, Grith Lykke; Beck-Nielsen, Signe Sparre; Pilecki, Bartosz; Duelund, Lars; Marcussen, Niels; Christesen, Henrik Thybo

    2016-01-01

    Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL) or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OH)D) determinations. After cesarean section at gestational day 19 (E19) or day 22 (E22), placental weight, birth weight, crown-rump-length (CRL), oxygenation (SaO2) at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR). S-25(OH)D was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p<0.0001). Compared to the controls, E19 VDL pups had lower birth weight (2.13 vs. 2.29g, p<0.001), lung weight (0.09 vs. 0.10g, p = 0.002), SaO2 (54% vs. 69%, p = 0.002) as well as reduced survival time (0.50 vs. 1.25h, p<0.0001). At E22, the VDL-induced pulmonary differences were leveled out, but VDL pups had lower CRL (4.0 vs. 4.5cm, p<0.0001). The phospholipid levels and the surfactant protein mRNA expression did not differ between the dietary groups. In conclusion, Vitamin D depletion led to lower oxygenation and reduced survival time in the preterm offspring, associated with reduced lung weight and birth weight. Further studies of vitamin D depletion in respiratory insufficiency in preterm neonates are warranted. PMID:27571350

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

    PubMed

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

    2014-08-01

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

  6. Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure

    PubMed Central

    SLIWOWSKA, J. H.; BARKER, J. M.; BARHA, C. K.; LAN, N.; WEINBERG, J.; GALEA, L. A. M.

    2016-01-01

    In adulthood, both alcohol (ethanol) and stress are known to suppress hippocampal neurogenesis in male rats. Similarly, most studies report that prenatal alcohol exposure (PAE) reduces cell proliferation and/or cell survival in the hippocampus of adult males. Furthermore, PAE is known to have marked effects on behavioral and hypothalamic–pituitary–adrenal (HPA) responsiveness to stressors. However, no studies have examined the modulation of adult hippocampal neurogenesis by stress in PAE animals. We hypothesized that, in accordance with previous data, PAE would suppress basal levels of adult hippocampal neurogenesis, and further that stress acting on a sensitized HPA axis would have greater adverse effects on adult hippocampal neurogenesis in PAE than in control rats. Adult male offspring from PAE, pair-fed (PF) control, and ad libitum-fed control (C) groups were subjected to restraint stress (9 days, 1 h/day) or left undisturbed. Rats were then injected with bromodeoxyuridine (BrdU) on day 10, perfused 24 h (proliferation) or 3 weeks (survival) later, and brains processed for BrdU immunohistochemistry. We found that (1) under non-stressed conditions, PAE rats had a small but statistically significant suppressive effect on levels of hippocampal neurogenesis and (2) unexpectedly, repeated restraint stress significantly reduced neurogenesis in C and PF, but not PAE rats. We speculate that the failure of PAE males to mount an appropriate (i.e. suppressive) neurogenic response to stressors, implies reduced plasticity and adaptability or resilience, which could impact negatively on hippocampal structure and function. PMID:20536332

  7. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.

    PubMed

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

    2014-12-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.

  8. Prenatal exposure to SKF-38393 alters the response to light of adult rats.

    PubMed

    Ferguson, S A; Kennaway, D J

    2000-05-15

    The current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT=zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.

  9. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  10. Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

    PubMed

    Guido, Luiza N; Fontelles, Camile C; Rosim, Mariana P; Pires, Vanessa C; Cozzolino, Silvia M F; Castro, Inar A; Bolaños-Jiménez, Francisco; Barbisan, Luis F; Ong, Thomas P

    2016-10-15

    Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.

  11. Effects of maternal exposure to cow's milk high or low in isoflavones on carcinogen-induced mammary tumorigenesis among rat offspring.

    PubMed

    Nielsen, Tina Skau; Purup, Stig; Wärri, Anni; Godschalk, Roger W; Hilakivi-Clarke, Leena

    2011-05-01

    We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin-like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis in female rat offspring. Pregnant Sprague-Dawley rats were given HIM, LIM, or tap water (control) from gestational day (GD) 11 until birth; hereafter all rats received tap water. Mammary tumorigenesis was induced by administrating 7,12-dimethylbenz[a]anthracene (DMBA) on postnatal day 50. No differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM group than in the HIM group. Puberty onset occurred earlier in the LIM offspring than in controls (P = 0.03). Although the high isoflavone content seemed to prevent the effect on circulating estradiol and IGF-1 levels and advanced puberty onset seen in the LIM group, HIM increased DMBA-DNA adducts in the mammary gland and tended to increase mammary tumorigenesis. In contrast, offspring exposed to LIM in utero, did not exhibit increased breast cancer risk, despite having higher estradiol and IGF-1 environment and consequently earlier puberty onset. These results indicate that the phytochemical content in the cow's milk, consumed by a pregnant dam, determines how milk affects the offspring.

  12. Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

    PubMed

    Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

    2011-10-01

    The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring.

  13. Olfactory impairment in an adult population: the Beaver Dam Offspring Study.

    PubMed

    Schubert, Carla R; Cruickshanks, Karen J; Fischer, Mary E; Huang, Guan-Hua; Klein, Barbara E K; Klein, Ronald; Pankow, James S; Nondahl, David M

    2012-05-01

    The objective of this study was to determine the prevalence of olfactory impairment and associated risk factors and the effects of olfactory impairment on dietary choices and quality of life. Odor identification was measured in 2838 participants aged 21-84 years (mean 49 years) in the Beaver Dam Offspring Study. The overall prevalence of olfactory impairment was 3.8%, increased with age (from 0.6% in those<35 years to 13.9% among those≥65 years) and was more common in men than women. In a multivariate model age (odds ratio [OR]=1.48, 95% confidence interval [CI]=1.33, 1.64 for every 5-year increase), nasal polyps or deviated septum (OR=2.69, 95% CI=1.62, 4.48), ankle-brachial index<0.9 (OR=3.62, 95% CI=1.45, 9.01), and smoking (women only) (OR=2.43, 95% CI=1.19, 4.98 ever smoked vs. never) were associated with an increased odds of olfactory impairment, whereas higher household income, ≥$50,000 versus <$50,000 per year, was associated with a decreased odds of olfactory impairment (OR=0.48, 95% CI=0.31, 0.73). Participants with olfactory impairment were less likely to report that food tasted as good as it used to, or that they experienced food flavors the same. There was no association between olfactory impairment and general health-related quality of life, depressive symptoms, or dietary choices. The prevalence of olfactory impairment was low in this largely middle-aged cohort, and some factors associated with olfactory impairment are potentially modifiable.

  14. The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress response in rat offspring exposed prenatally to polyriboinosinic-polyribocytidylic-acid (PIC).

    PubMed

    Maayan, Rachel; Ram, Edward; Biton, Doron; Cohen, Hagit; Baharav, Ehud; Strous, Rael D; Weizman, Abraham

    2012-07-11

    Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic-polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions.

  15. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

    PubMed

    Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

    2015-06-01

    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

  16. Risk Factors Associated with Aortic and Carotid Intimal-Medial Thickness in Adolescents and Young Adults: the Muscatine Offspring Study

    PubMed Central

    Dawson, Jeffrey D.; Sonka, Milan; Blecha, Mary Beth; Lin, Wenjiao; Davis, Patricia H.

    2009-01-01

    Objectives To determine whether cardiovascular risk factors are associated with aortic and carotid intimal-medial thickness (aIMT and cIMT) in adolescents and young adults. Background Atherosclerotic lesions begin developing in youth, first in the distal abdominal aorta and later in the carotid arteries. Knowledge of how risk factors relate to aIMT and cIMT may help in the design of early interventions to prevent cardiovascular disease. Methods Participants were 635 members of the Muscatine Offspring cohort. The mean aIMT and cIMT were measured using an automated reading program. Results The means (SDs) of aIMT and cIMT were 0.63 (0.14) mm and 0.49 (0.04) mm, respectively. In adolescents (ages 11 to 17), aIMT was associated with triglycerides, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist/hip ratio, after adjusting for age, gender, and height. In young adults (ages 18 to 34), aIMT was associated with those same five risk factors, plus HDL-cholesterol and pulse pressure. In adolescents, cIMT was associated with SBP, pulse pressure, heart rate, BMI, and waist/hip ratio. In young adults, cIMT was associated total cholesterol, LDL-cholesterol, triglycerides, SBP, .DBP, BMI, waist/hip ratio, and HbA1C. In both age groups, aIMT and cIMT were significantly correlated with the PDAY coronary artery risk score. Conclusions Both aIMT and cIMT are associated with cardiovascular risk factors. Using aIMT in adolescents gives information beyond that obtained from cIMT alone. Measurement of aIMT and cIMT may help identify those at risk for premature cardiovascular disease. PMID:19520251

  17. Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

    PubMed

    Arentson-Lantz, Emily J; Zou, Mi; Teegarden, Dorothy; Buhman, Kimberly K; Donkin, Shawn S

    2016-09-01

    Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (P<.05) at weaning (50.3, 29.6 vs 59.1±0.8 g) and at 18 weeks of age (420, 369 vs 464±10.9 g). At 18 weeks of age, offspring from fructose dams expressed greater quantities (P<.05) of intestinal Pgc1a messenger RNA compared with offspring from control or low-protein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (P<.05) consumption increased expression of Pgc1a in offspring liver (7.24, 2.22 vs 1.22; confidence interval, 2.11-3.45). These data indicate that maternal fructose feeding is a programming model that shares some features of maternal protein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts.

  18. The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

    PubMed

    Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S

    2016-06-01

    Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data.

  19. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine.

    PubMed

    Šlamberová, Romana; Macúchová, Eva; Nohejlová, Kateryna; Štofková, Andrea; Jurčovičová, Jana

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  20. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect

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

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  1. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase.

    PubMed

    Ma, Noelle; Nicholson, Catherine J; Wong, Michael; Holloway, Alison C; Hardy, Daniel B

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway.

  2. [Radioprotective effect of drinking sulfate mineral water on spermatogenesis in offspring of irradiated male rats].

    PubMed

    Korolev, Iu N; Geniatulina, M S; Nikulina, L A; Kurilo, L F

    2003-01-01

    Histological and electron-microscopic studies of a radioprotective action of drinking sulphate mineral water (SMW) on spermatogenesis of irradiated male rats' progeny have found that SMW used before radiation (2 Gy) and 10 days after it is able to reduce postradiation sequelae in the progeny (2-5 month and 1.5 year old rats) testes.

  3. Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats.

    PubMed

    Younes-Rapozo, V; Moura, E G; Manhães, A C; Pinheiro, C R; Carvalho, J C; Barradas, P C; de Oliveira, E; Lisboa, P C

    2015-12-01

    Astrocytes and microglia, the immune competent cells of central nercous system, can be activated in response to metabolic signals such as obesity and hyperleptinaemia. In rats, maternal exposure to nicotine during lactation leads to central obesity, hyperleptinaemia, leptin resistance and alterations in hypothalamic neuropeptides in the offspring during adulthood. In the present study, we studied the activation of astrocytes and microglia, as well as the pattern of inflammatory mediators, in adult offspring of this experimental model. On postnatal day 2 (P2), osmotic minipumps releasing nicotine (NIC) (-6 mg/kg/day) or saline for 14 days were s.c. implanted in dams. Male offspring were killed on P180 and hypothalamic immunohistochemistry, retroperitoneal white adipose tissue (WAT) polymerase chain reaction analysis and multiplex analysis for plasma inflammatory mediators were carried out. At P180, NIC astrocyte cell number was higher in the arcuate nucleus (ARC) (medial: +82%; lateral: +110%), in the paraventricular nucleus (PVN) (+144%) and in the lateral hypothalamus (+121%). NIC glial fibrillary acidic protein fibre density was higher in the lateral ARC (+178%) and in the PVN (+183%). Interleukin-6 was not affected in the hypothalamus. NIC monocyte chemotactic protein 1 was only higher in the periventricular nucleus (+287%). NIC microglia (iba-1-positive) cell number was higher (+68%) only in the PVN, as was the chemokine (C-X3-C motif) receptor 1 density (+93%). NIC interleukin-10 was lower in the WAT (-58%) and plasma (-50%). Thus, offspring of mothers exposed to nicotine during lactation present hypothalamic astrogliosis at adulthood and microgliosis in the PVN.

  4. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring

    PubMed Central

    Cyrus Chu, C.Y.; Lee, Ronald D.

    2013-01-01

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages. PMID:23648187

  5. On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring.

    PubMed

    Cyrus, Chu C Y; Lee, Ronald D

    2013-09-07

    We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages.

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

    PubMed

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

    2003-09-01

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

  7. Prenatal exposure to glucocorticoids affects body weight, serum leptin levels, and hypothalamic neuropeptide-Y expression in pre-pubertal female rat offspring.

    PubMed

    Iwasa, Takeshi; Matsuzaki, Toshiya; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Kawami, Takako; Murakami, Masahiro; Yamasaki, Mikio; Kato, Takeshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2014-08-01

    Glucocorticoid secretion is a key endocrine response to stress. It has been reported that prenatal stress induces long-lasting alterations in body weight regulation systems, which persist after the stress has ceased. In this study, the long-term effects of prenatal glucocorticoid exposure on body weight changes and the expression of appetite-regulating factors were examined in female rats. Pregnant rats were given normal drinking water (control) or dexamethasone (1 μg/mL) dissolved in drinking water (DEX) from day 13 of pregnancy until delivery. Then, the body weight change, serum leptin levels, and hypothalamic NPY mRNA levels of their offspring were examined. The DEX dams gained significantly less body weight during pregnancy than the control dams. The DEX dams' offspring exhibited a significantly lower birth weight than the offspring of the control dams, and the same was true for body weight at postnatal days 20 and 28. The offspring of the DEX dams displayed significantly higher serum leptin levels and significantly lower hypothalamic NPY mRNA levels compared with the offspring of the control dams. Significant inverse correlations were detected between body weight and the serum leptin level, and between the serum leptin level and the hypothalamic NPY mRNA level. On the other hand, a significant positive correlation was detected between body weight and the hypothalamic NPY mRNA level. These results indicate that leptin production is increased in a long-lasting manner in offspring exposed to glucocorticoids during the prenatal period and that this results in attenuated body weight gain and hypothalamic NPY expression during the pre-pubertal period.

  8. Maternal dietary loads of α-tocopherol differentially influence fear conditioning and spatial learning in adult offspring.

    PubMed

    Ambrogini, Patrizia; Ciuffoli, Stefano; Lattanzi, Davide; Minelli, Andrea; Bucherelli, Corrado; Baldi, Elisabetta; Betti, Michele; Cuppini, Riccardo

    2011-10-24

    α-Tocopherol, the main component of vitamin E, is well known to be a radical scavenger, so an increased intake of vitamin E is recommended in complicated pregnancy, to prevent possible fetus damage by free radical. In a previous work, we found that maternal α-tocopherol supplementation affects PKC-mediated cellular signaling and hippocampal synaptic plasticity in developing brain; the latter effect persists in adulthood. Here, adult rats maternally exposed to supranutritional doses of α-tocopherol were evaluated for Contextual Fear Conditioning and spatial learning in Morris Water Maze, two different hippocampus-dependent learning tasks. Moreover, anxiety, spontaneous activity, and explorative drive were also evaluated as factors potentially affecting learning performance. Treated rats showed a different behavior with respect to controls: performance in Contextual Fear Conditioning was improved, while spatial learning tested in Morris Water Maze, was impaired. The improvement of fear response was not ascribable to differences in anxiety level and/or spontaneous activity; thus it appears to be a specific effect of α-tocopherol overloading during brain development. On the contrary, the impaired performance in Morris Water Maze exhibited by treated rats can be in part explained by their enhanced explorative drive. Although extrapolation from rats to humans is difficult, a caveat in assuming supranutritional doses of vitamin E in pregnancy arises from this study.

  9. Too risky to settle: avian community structure changes in response to perceived predation risk on adults and offspring

    USGS Publications Warehouse

    Hua, Fangyuan; Fletcher, Robert J.; Sieving, Kathryn E.; Dorazio, Robert M.

    2013-01-01

    Predation risk is widely hypothesized as an important force structuring communities, but this potential force is rarely tested experimentally, particularly in terrestrial vertebrate communities. How animals respond to predation risk is generally considered predictable from species life-history and natural-history traits, but rigorous tests of these predictions remain scarce. We report on a large-scale playback experiment with a forest bird community that addresses two questions: (i) does perceived predation risk shape the richness and composition of a breeding bird community? And (ii) can species life-history and natural-history traits predict prey community responses to different types of predation risk? On 9 ha plots, we manipulated cues of three avian predators that preferentially prey on either adult birds or offspring, or both, throughout the breeding season. We found that increased perception of predation risk led to generally negative responses in the abundance, occurrence and/or detection probability of most prey species, which in turn reduced the species richness and shifted the composition of the breeding bird community. Species-level responses were largely predicted from the key natural-history trait of body size, but we did not find support for the life-history theory prediction of the relationship between species' slow/fast life-history strategy and their response to predation risk.

  10. Prenatal stress alters diazepam withdrawal syndrome and 5HT1A receptor expression in the raphe nuclei of adult rats.

    PubMed

    Lakehayli, S; Said, N; El Khachibi, M; El Ouahli, M; Nadifi, S; Hakkou, F; Tazi, A

    2016-08-25

    Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats.

  11. The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

    ERIC Educational Resources Information Center

    Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

  12. Placental and lactational transfer of decabromodiphenyl ether and 2,2',4,4'-tetrabromodiphenyl ether in dam-offspring pairs of Sprague-Dawley rats.

    PubMed

    Shin, Mi-Yeon; Lee, Sunggyu; Choi, Hyeyoung; Jeong, Da-In; Moon, Hyo-Bang; Kim, Sungkyoon

    2017-01-31

    Although several studies have conducted maternal transfer of individual PBDE congener in experimental animals, there is a paucity of research on differences in maternal transfer of PBDE congeners. The purpose of the study was to investigate and compare placental and lactational transfer of BDE 47, -209 and its metabolites in rat dam-offspring pairs following repeated administration of BDE 47 and -209. (13)C-BDE 47, BDE 209 and its debrominated congeners were detected both in dam serum and offspring body, which indicates that PBDEs can be maternally transferred. In addition, BDE 196 and -197 appeared in offspring body earlier than in maternal serum, which suggests that debromination can be occur in offspring body. BDE 209 increased in both dam and offspring while levels of (13)C-BDE 47 was not increased in dam serum. 13C-BDE 47 seems to be stored in breast milk rather than in maternal serum, which can be assumed through the drastic increase of the congener in suckling pups. The magnitude of lactational transfer of the administered congeners was greater than that of placental transfer. And (13)C-BDE 47 was relatively more transferred to suckling pups than BDE 209 through breastfeeding.

  13. Experimental comparison of the reproductive outcomes and early development of the offspring of rats given five common types of drinking water.

    PubMed

    Zeng, Hui; Chen, Ji-an; Liu, Lin; Wang, Da-hua; Fu, Wen-juan; Wang, Ling-qiao; Luo, Jiao-hua; Zhang, Liang; Tan, Yao; Qiu, Zhi-qun; Huang, Yu-jing; Shu, Wei-qun

    2014-01-01

    Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague-Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring's learning and memory abilities (OLMA); the lowest offspring survi