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Sample records for exposure alters l-a-amino-3-hydroxy-5-methyl-4-isoxazole

  1. Marijuana exposure and pulmonary alterations in primates.

    Science.gov (United States)

    Fligiel, S E; Beals, T F; Tashkin, D P; Paule, M G; Scallet, A C; Ali, S F; Bailey, J R; Slikker, W

    1991-11-01

    As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

  2. Chronic bisphenol A exposure alters behaviors of zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Wang, Ju; Wang, Xia; Xiong, Can; Liu, Jian; Hu, Bing; Zheng, Lei

    2015-01-01

    The adult zebrafish (Danio rerio) were exposed to treated-effluent concentration of bisphenol A (BPA) or 17β-estradiol (E2) for 6 months to evaluate their effects on behavioral characteristics: motor behavior, aggression, group preference, novel tank test and light/dark preference. E2 exposure evidently dampened fish locomotor activity, while BPA exposure had no marked effect. Interestingly, BPA-exposed fish reduced their aggressive behavior compared with control or E2. Both BPA and E2 exposure induced a significant decrease in group preference, as well as a weaker adaptability to new environment, exhibiting lower latency to reach the top, more entries to the top, longer time spent in the top, fewer frequent freezing, and fewer erratic movements. Furthermore, the circadian rhythmicity of light/dark preference was altered by either BPA or E2 exposure. Our results suggest that chronic exposure of treated-effluent concentration BPA or E2 induced various behavioral anomalies in adult fish and enhanced ecological risk to wildlife. - Highlights: • BPA exposure induces various adult behavioral anomalies. • BPA exposure decreases social interaction and environmental adaptation of zebrafish. • BPA exposure increases ecological risk to wildlife. - Chronic bisphenol A exposure alters zebrafish behaviors.

  3. Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

    Science.gov (United States)

    Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

    2010-11-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  5. Cigarette smoke exposure-associated alterations to noncoding RNA

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    Matthew Alan Maccani

    2012-04-01

    Full Text Available Environmental exposures vary by timing, severity, and frequency and may have a number of deleterious effects throughout the life course. The period of in utero development, for example, is one of the most crucial stages of development during which adverse environmental exposures can both alter the growth and development of the fetus as well as lead to aberrant fetal programming, increasing disease risk. During fetal development and beyond, the plethora of exposures, including nutrients, drugs, stress, and trauma, influence health, development, and survival. Recent research in environmental epigenetics has investigated the roles of environmental exposures in influencing epigenetic modes of gene regulation during pregnancy and at various stages of life. Many relatively common environmental exposures, such as cigarette smoking, alcohol consumption, and drug use, may have consequences for the expression and function of noncoding RNA (ncRNA, important post-transcriptional regulators of gene expression. A number of ncRNA have been discovered, including microRNA (miRNA, Piwi-interacting RNA (piRNA, and long noncoding RNA (long ncRNA. The best-characterized species of ncRNA are miRNA, the mature forms of which are ~22 nucleotides in length and capable of post-transcriptionally regulating target mRNA utilizing mechanisms based largely on the degree of complementarity between miRNA and target mRNA. Because miRNA can still negatively regulate gene expression when imperfectly base-paired with a target mRNA, a single miRNA can have a large number of potential mRNA targets and can regulate many different biological processes critical for health and development. The following review analyzes the current literature detailing links between cigarette smoke exposure and aberrant expression and function of noncoding RNA, assesses how such alterations may have consequences throughout the life course, and proposes future directions for this intriguing field of

  6. Tributyltin exposure alters cytokine levels in mouse serum.

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  7. Tributyltin Exposure Alters Cytokine Levels in Mouse Serum

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T.; Shanker, Anil; Whalen, Margaret M.

    2016-01-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines. PMID:27602597

  8. Self-generated visual imagery alters the mere exposure effect.

    Science.gov (United States)

    Craver-Lemley, Catherine; Bornstein, Robert F

    2006-12-01

    To determine whether self-generated visual imagery alters liking ratings of merely exposed stimuli, 79 college students were repeatedly exposed to the ambiguous duck-rabbit figure. Half the participants were told to picture the image as a duck and half to picture it as a rabbit. When participants made liking ratings of both disambiguated versions of the figure, they rated the version consistent with earlier encoding more positively than the alternate version. Implications of these findings for theoretical models of the exposure effect are discussed.

  9. Altering user' acceptance of automation through prior automation exposure.

    Science.gov (United States)

    Bekier, Marek; Molesworth, Brett R C

    2017-06-01

    Air navigation service providers worldwide see increased use of automation as one solution to overcome the capacity constraints imbedded in the present air traffic management (ATM) system. However, increased use of automation within any system is dependent on user acceptance. The present research sought to determine if the point at which an individual is no longer willing to accept or cooperate with automation can be manipulated. Forty participants underwent training on a computer-based air traffic control programme, followed by two ATM exercises (order counterbalanced), one with and one without the aid of automation. Results revealed after exposure to a task with automation assistance, user acceptance of high(er) levels of automation ('tipping point') decreased; suggesting it is indeed possible to alter automation acceptance. Practitioner Summary: This paper investigates whether the point at which a user of automation rejects automation (i.e. 'tipping point') is constant or can be manipulated. The results revealed after exposure to a task with automation assistance, user acceptance of high(er) levels of automation decreased; suggesting it is possible to alter automation acceptance.

  10. Alteration of gene expression by alcohol exposure at early neurulation.

    Science.gov (United States)

    Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

    2011-02-21

    We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

  11. Prenatal methadone exposure is associated with altered neonatal brain development

    Directory of Open Access Journals (Sweden)

    Victoria J. Monnelly

    Full Text Available Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development is altered among newborn infants whose mothers were prescribed methadone.20 methadone-exposed neonates born after 37weeks' postmenstrual age (PMA and 20 non-exposed controls underwent diffusion MRI at mean PMA of 39+2 and 41+1weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA data between exposed and non-exposed neonates.Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF and the internal and external capsules after adjustment for GA at MRI (p<0.05, TFCE corrected. Median FA across the white matter skeleton was 12% lower among methadone-exposed infants. Mean head circumference (HC z-scores were lower in the methadone-exposed group (−0.52 (0.99 vs 1.15 (0.84, p<0.001; after adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug use among cases was common.Prenatal methadone exposure is associated with microstructural alteration in major white matter tracts, which is present at birth and is independent of head growth. Although the findings cannot be attributed to methadone per se, the data indicate that further research to determine optimal management of opioid use disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function. Keywords: Prenatal, Methadone, Brain, Neonate, MRI, Opioid

  12. Alexithymia tendencies and mere exposure alter social approachability judgments.

    Science.gov (United States)

    Campbell, Darren W; McKeen, Nancy A

    2011-04-01

    People have a fundamental motivation for social connection and social engagement, but how do they decide whom to approach in ambiguous social situations? Subjective feelings often influence such decisions, but people vary in awareness of their feelings. We evaluated two opposing hypotheses based on visual familiarity effects and emotional awareness on social approachability judgments. These hypotheses differ in their interpretation of the familiarity or mere exposure effect with either an affective or cognitive interpretation. The responses of our 128-student sample supported the cognitive interpretation. Lower emotional awareness or higher alexithymia was associated with higher approachability judgments to familiarized faces and lower approachability judgments to novel faces. These findings were independent of the Big Five personality factors. The results indicate that individual differences in emotional awareness should be integrated into social decision-making models. The results also suggest that cognitive-perceptual alterations may underlie the poorer social outcomes associated with alexithymia. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

  13. Exposure to buffer solution alters tendon hydration and mechanics.

    Science.gov (United States)

    Safa, Babak N; Meadows, Kyle D; Szczesny, Spencer E; Elliott, Dawn M

    2017-08-16

    A buffer solution is often used to maintain tissue hydration during mechanical testing. The most commonly used buffer solution is a physiological concentration of phosphate buffered saline (PBS); however, PBS increases the tissue's water content and decreases its tensile stiffness. In addition, solutes from the buffer can diffuse into the tissue and interact with its structure and mechanics. These bathing solution effects can confound the outcome and interpretation of mechanical tests. Potential bathing solution artifacts, including solute diffusion, and their effect on mechanical properties, are not well understood. The objective of this study was to measure the effects of long-term exposure of rat tail tendon fascicles to several concentrations (0.9-25%) of NaCl, sucrose, polyethylene glycol (PEG), and SPEG (NaCl+PEG) solutions on water content, solute diffusion, and mechanical properties. We found that with an increase in solute concentration the apparent water content decreased for all solution types. Solutes diffused into the tissue for NaCl and sucrose, however, no solute diffusion was observed for PEG or SPEG. The mechanical properties changed for both NaCl solutions, in particular after long-term (8h) incubation the modulus and equilibrium stress decreased compared to short-term (15min) for 25% NaCl, and the cross sectional area increased for 0.9% NaCl. However, the mechanical properties were unchanged for both PEG and SPEG except for minor alterations in stress relaxation parameters. This study shows that NaCl and sucrose buffer solutions are not suitable for long-term mechanical tests. We therefore propose using PEG or SPEG as alternative buffer solutions that after long-term incubation can maintain tissue hydration without solute diffusion and produce a consistent mechanical response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  15. Mere exposure alters category learning of novel objects

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    Jonathan R Folstein

    2010-08-01

    Full Text Available We investigated how mere exposure to complex objects with correlated or uncorrelated object features affects later category learning of new objects not seen during exposure. Correlations among pre-exposed object dimensions influenced later category learning. Unlike other published studies, the collection of pre-exposed objects provided no information regarding the categories to be learned, ruling out unsupervised or incidental category learning during pre-exposure. Instead, results are interpreted with respect to statistical learning mechanisms, providing one of the first demonstrations of how statistical learning can influence visual object learning.

  16. Mere exposure alters category learning of novel objects.

    Science.gov (United States)

    Folstein, Jonathan R; Gauthier, Isabel; Palmeri, Thomas J

    2010-01-01

    We investigated how mere exposure to complex objects with correlated or uncorrelated object features affects later category learning of new objects not seen during exposure. Correlations among pre-exposed object dimensions influenced later category learning. Unlike other published studies, the collection of pre-exposed objects provided no information regarding the categories to be learned, ruling out unsupervised or incidental category learning during pre-exposure. Instead, results are interpreted with respect to statistical learning mechanisms, providing one of the first demonstrations of how statistical learning can influence visual object learning.

  17. ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

    OpenAIRE

    Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

    2010-01-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

  18. Neuropsychological alterations in mercury intoxication persist several years after exposure.

    Science.gov (United States)

    Zachi, Elaine Cristina; Taub, Anita; Faria, Marcília de Araújo Medrado; Ventura, Dora Fix

    2008-01-01

    Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (Precovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years.

  19. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

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    Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  20. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    International Nuclear Information System (INIS)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G.; Flaws, Jodi A.

    2016-01-01

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  1. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  2. Neuropsychological alterations in mercury intoxication persist several years after exposure

    Directory of Open Access Journals (Sweden)

    Elaine Cristina Zachi

    Full Text Available Abstract Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. Objectives: The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Methods: Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. Results: At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (P<0.05. Paired comparisons of neuropsychological functioning within the exposed group at baseline and 1.5 years later showed poorer immediate memory performance (P<0.05. There were no differences on other measures. Conclusions: Although the literature show signs of recovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years.

  3. Prenatal cadmium exposure alters postnatal immune cell development and function

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    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B., E-mail: jbarnett@hsc.wvu.edu

    2012-06-01

    Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can

  4. Passive Heat Exposure Alters Perception and Executive Function

    Directory of Open Access Journals (Sweden)

    Rachel A. Malcolm

    2018-05-01

    Full Text Available Findings regarding the influence of passive heat exposure on cognitive function remain equivocal due to a number of methodological issues including variation in the domains of cognition examined. In a randomized crossover design, forty-one male participants completed a battery of cognitive function tests [Visual Search, Stroop, Corsi Blocks and Rapid Visual Information Processing (RVIP tests] prior to and following 1 h of passive rest in either hot (39.6 ± 0.4°C, 50.8 ± 2.3% Rh or moderate (21.2 ± 1.8°C, 41.9 ± 11.4% Rh conditions. Subjective feelings of heat exposure, arousal and feeling were assessed alongside physiological measures including core temperature, skin temperature and heart rate, at baseline and throughout the protocol. Response times were slower in the hot trial on the simple (main effect of trial, P < 0.001 and complex (main effect of trial, P < 0.001 levels of the Stroop test (Hot: 872 ± 198 ms; Moderate: 834 ± 177 ms and the simple level of the visual search test (Hot: 354 ± 54 ms; Moderate: 331 ± 47 ms (main effect of trial, P < 0.001. Participants demonstrated superior accuracy on the simple level of the Visual Search test in the hot trial (Hot: 98.5 ± 3.1%; Moderate: 97.4 ± 3.6% (main effect of trial, P = 0.035. Participants also demonstrated an improvement in accuracy on the complex level of the visual search test following 1 h passive heat exposure (Pre: 96.8 ± 5.9%; Post: 98.1 ± 3.1%, whilst a decrement was seen across the trial in the moderate condition (Pre: 97.7 ± 3.5; Post: 97.0 ± 5.1% (time*trial interaction, P = 0.029. No differences in performance were observed on the RVIP or Corsi Blocks tests (all P > 0.05. Subjective feelings of thermal sensation and felt arousal were higher, feeling was lower in the hot trial, whilst skin temperature, core temperature and heart rate were higher (main effects of trial, all P < 0.001. The findings of the present study suggest that response times for perception

  5. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes

    Energy Technology Data Exchange (ETDEWEB)

    Moore-Ambriz, Teresita Rocio; Acuña-Hernández, Deyanira Guadalupe; Ramos-Robles, Brenda [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, México D.F. 07360, México (Mexico); Sánchez-Gutiérrez, Manuel [Área Académica de Medicina, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo 42000, México (Mexico); Santacruz-Márquez, Ramsés; Sierra-Santoyo, Adolfo [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, México D.F. 07360, México (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, México D.F. 07738, México (Mexico); and others

    2015-12-15

    Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first evaluated whether BPA alters ovulation by affecting folliculogenesis, the number of corpora lutea or eggs shed to the oviduct, ovarian gonadotropin responsiveness, hormone levels, and estrous cyclicity. Because it has been suggested (but not directly confirmed) that BPA exerts toxic effects on the fertilization ability of oocytes, a second aim was to evaluate whether BPA impacts the oocyte fertilization rate using an in vitro fertilization assay and mating. The possible effects on early zygote development were also examined. Young adult female C57BL/6J mice (39 days old) were orally dosed with corn oil (vehicle) or 50 μg/kg bw/day BPA for a period encompassing the first three reproductive cycles (12–15 days). BPA exposure did not alter any parameters related to ovulation. Moreover, BPA exposure reduced the percentage of fertilized oocytes after either in vitro fertilization or mating, but it did not alter the zygotic stages. The data indicate that exposure to the reference dose of BPA does not impact ovulation but that it does influence the oocyte quality in terms of its fertilization ability. - Highlights: • Bisphenol A targets the fertilization ability of oocytes. • Bisphenol A does not alter ovulation. • Young adult females may be susceptible to the effects of bisphenol A on fertilization.

  6. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes

    International Nuclear Information System (INIS)

    Moore-Ambriz, Teresita Rocio; Acuña-Hernández, Deyanira Guadalupe; Ramos-Robles, Brenda; Sánchez-Gutiérrez, Manuel; Santacruz-Márquez, Ramsés; Sierra-Santoyo, Adolfo; Piña-Guzmán, Belem

    2015-01-01

    Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first evaluated whether BPA alters ovulation by affecting folliculogenesis, the number of corpora lutea or eggs shed to the oviduct, ovarian gonadotropin responsiveness, hormone levels, and estrous cyclicity. Because it has been suggested (but not directly confirmed) that BPA exerts toxic effects on the fertilization ability of oocytes, a second aim was to evaluate whether BPA impacts the oocyte fertilization rate using an in vitro fertilization assay and mating. The possible effects on early zygote development were also examined. Young adult female C57BL/6J mice (39 days old) were orally dosed with corn oil (vehicle) or 50 μg/kg bw/day BPA for a period encompassing the first three reproductive cycles (12–15 days). BPA exposure did not alter any parameters related to ovulation. Moreover, BPA exposure reduced the percentage of fertilized oocytes after either in vitro fertilization or mating, but it did not alter the zygotic stages. The data indicate that exposure to the reference dose of BPA does not impact ovulation but that it does influence the oocyte quality in terms of its fertilization ability. - Highlights: • Bisphenol A targets the fertilization ability of oocytes. • Bisphenol A does not alter ovulation. • Young adult females may be susceptible to the effects of bisphenol A on fertilization.

  7. Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

    Science.gov (United States)

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2015-09-01

    The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

    Directory of Open Access Journals (Sweden)

    Silvers Janelle M

    2006-04-01

    Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

  9. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  10. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS

    Science.gov (United States)

    GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS. D.K. Tarka*1,2, J.D. Suarez*2, N.L. Roberts*2, J.M. Rogers*1,2, M.P. Hardy3, and G.R. Klinefelter1,2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC; 2USEPA,...

  11. Inorganic mercury exposure in drinking water alters essential metal homeostasis in pregnant rats without altering rat pup behavior.

    Science.gov (United States)

    Oliveira, Cláudia S; Oliveira, Vitor A; Costa, Lidiane M; Pedroso, Taíse F; Fonseca, Mariana M; Bernardi, Jamile S; Fiuza, Tiago L; Pereira, Maria E

    2016-10-01

    The aim of this work was to investigate the effects of HgCl 2 exposure in the doses of 0, 10 and 50μg Hg 2+ /mL in drinking water during pregnancy on tissue essential metal homeostasis, as well as the effects of HgCl 2 exposure in utero and breast milk on behavioral tasks. Pregnant rats exposed to both inorganic mercury doses presented high renal Hg content and an increase in renal Cu and hepatic Zn levels. Mercury exposure increased fecal Hg and essential metal contents. Pups exposed to inorganic Hg presented no alterations in essential metal homeostasis or in behavioral task markers of motor function. In conclusion, this work showed that the physiologic pregnancy and lactation states protected the offspring from adverse effects of low doses of Hg 2+ . This protection is likely to be related to the endogenous scavenger molecule, metallothionein, which may form an inert complex with Hg 2+ . Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

    Science.gov (United States)

    Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

    2018-01-01

    Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions

  13. Hurricane Sandy Exposure Alters the Development of Neural Reactivity to Negative Stimuli in Children.

    Science.gov (United States)

    Kessel, Ellen M; Nelson, Brady D; Kujawa, Autumn; Hajcak, Greg; Kotov, Roman; Bromet, Evelyn J; Carlson, Gabrielle A; Klein, Daniel N

    2018-03-01

    This study examined whether exposure to Hurricane Sandy-related stressors altered children's brain response to emotional information. An average of 8 months (M age  = 9.19) before and 9 months after (M age  = 10.95) Hurricane Sandy, 77 children experiencing high (n = 37) and low (n = 40) levels of hurricane-related stress exposure completed a task in which the late positive potential, a neural index of emotional reactivity, was measured in response to pleasant and unpleasant, compared to neutral, images. From pre- to post-Hurricane Sandy, children with high stress exposure failed to show the same decrease in emotional reactivity to unpleasant versus neutral stimuli as those with low stress exposure. Results provide compelling evidence that exposure to natural disaster-related stressors alters neural emotional reactivity to negatively valenced information. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

  14. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    Science.gov (United States)

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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. © The Author(s) 2014.

  16. Embryo-larval exposure to atrazine reduces viability and alters oxidative stress parameters in Drosophila melanogaster.

    Science.gov (United States)

    Figueira, Fernanda Hernandes; Aguiar, Lais Mattos de; Rosa, Carlos Eduardo da

    2017-01-01

    The herbicide atrazine has been used worldwide with subsequent residual contamination of water and food, which may cause adverse effects on non-target organisms. Animal exposure to this herbicide may affect development, reproduction and energy metabolism. Here, the effects of atrazine regarding survival and redox metabolism were assessed in the fruit fly D. melanogaster exposed during embryonic and larval development. The embryos (newly fertilized eggs) were exposed to different atrazine concentrations (10μM and 100μM) in the diet until the adult fly emerged. Pupation and emergence rates, developmental time and sex ratio were determined as well as oxidative stress parameters and gene expression of the antioxidant defence system were evaluated in newly emerged male and female flies. Atrazine exposure reduced pupation and emergence rates in fruit flies without alterations to developmental time and sex ratio. Different redox imbalance patterns were observed between males and females exposed to atrazine. Atrazine caused an increase in oxidative damage, reactive oxygen species generation and antioxidant capacity and decreased thiol-containing molecules. Further, atrazine exposure altered the mRNA expression of antioxidant genes (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2). Reductions in fruit fly larval and pupal viability observed here are likely consequences of the oxidative stress induced by atrazine exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Diesel exhaust particle exposure in vitro alters monocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Nazia Chaudhuri

    Full Text Available Air pollution by diesel exhaust particles is associated with elevated mortality and increased hospital admissions in individuals with respiratory diseases such as asthma and chronic obstructive pulmonary disease. During active inflammation monocytes are recruited to the airways and can replace resident alveolar macrophages. We therefore investigated whether chronic fourteen day exposure to low concentrations of diesel exhaust particles can alter the phenotype and function of monocytes from healthy individuals and those with chronic obstructive pulmonary disease. Monocytes were purified from the blood of healthy individuals and people with a diagnosis of chronic obstructive pulmonary disease. Monocyte-derived macrophages were generated in the presence or absence of diesel exhaust particles and their phenotypes studied through investigation of their lifespan, cytokine generation in response to Toll like receptor agonists and heat killed bacteria, and expression of surface markers. Chronic fourteen day exposure of monocyte-derived macrophages to concentrations of diesel exhaust particles >10 µg/ml caused mitochondrial and lysosomal dysfunction, and a gradual loss of cells over time both in healthy and chronic obstructive pulmonary disease individuals. Chronic exposure to lower concentrations of diesel exhaust particles impaired CXCL8 cytokine responses to lipopolysaccharide and heat killed E. coli, and this phenotype was associated with a reduction in CD14 and CD11b expression. Chronic diesel exhaust particle exposure may therefore alter both numbers and function of lung macrophages differentiating from locally recruited monocytes in the lungs of healthy people and patients with chronic obstructive pulmonary disease.

  18. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    Directory of Open Access Journals (Sweden)

    Ivy N Cheung

    Full Text Available Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux. Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group or 10.5 hours after wake (n = 10; evening group. All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR and area under the curve (AUC for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism.

  19. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    International Nuclear Information System (INIS)

    Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.

    2015-01-01

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O 3 ) or HDMA/ozone (HDMA + O 3 ) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O 3 alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  20. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    Energy Technology Data Exchange (ETDEWEB)

    Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)

    2015-02-15

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  1. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

    Science.gov (United States)

    Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

    2006-09-01

    Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

  2. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology

    Directory of Open Access Journals (Sweden)

    Brian R. Mullen

    2016-06-01

    Full Text Available Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors—reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon—gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology.

  3. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity.

    Science.gov (United States)

    Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J

    2017-03-31

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues.

  4. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

    2003-03-01

    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  5. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

    Science.gov (United States)

    Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

    2010-10-01

    Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

  6. Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs.

    Science.gov (United States)

    Schuster, Andrew; Skinner, Michael K; Yan, Wei

    Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.

  7. Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2015-05-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. © 2013 Wiley Periodicals, Inc.

  8. In vitro exposure of Ulva lactuca Linnaeus (Chlorophyta) to gasoline - Biochemical and morphological alterations.

    Science.gov (United States)

    Pilatti, Fernanda Kokowicz; Ramlov, Fernanda; Schmidt, Eder Carlos; Kreusch, Marianne; Pereira, Débora Tomazi; Costa, Christopher; de Oliveira, Eva Regina; Bauer, Cláudia M; Rocha, Miguel; Bouzon, Zenilda Laurita; Maraschin, Marcelo

    2016-08-01

    Refined fuels have considerable share of pollution of marine ecosystems. Gasoline is one of the most consumed fuel worldwide, but its effects on marine benthic primary producers are poorly investigated. In this study, Ulva lactuca was chosen as a biological model due to its cosmopolitan nature and tolerance to high levels and wide range of xenobiotics and our goal was to evaluate the effects of gasoline on ultrastructure and metabolism of that seaweed. The experimental design consisted of in vitro exposure of U. lactuca to four concentrations of gasoline (0.001%, 0.01%, 0.1%, and 1.0%, v/v) over 30 min, 1 h, 12 h, and 24 h, followed by cytochemical, SEM, and biochemical analysis. Increase in the number of cytoplasmic granules, loss of cell turgor, cytoplasmic shrinkage, and alterations in the mucilage were some of the ultrastructural alterations observed in thalli exposed to gasoline. Decrease in carotenoid and polyphenol contents, as well as increase of soluble sugars and starch contents were associated with the time of exposure to the xenobiotic. In combination, the results revealed important morphological and biochemical alterations in the phenotype of U. lactuca upon acute exposure to gasoline. This seaweed contain certain metabolites assigned as candidates to biomarkers of the environmental stress investigated and it is thought to be a promise species for usage in coastal ecosystems perturbation monitoring system. In addition, the findings suggest that U. lactuca is able to metabolize gasoline hydrocarbons and use them as energy source, acting as bioremediator of marine waters contaminated by petroleum derivatives. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    International Nuclear Information System (INIS)

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-01-01

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

  10. Parental diuron-exposure alters offspring transcriptome and fitness in Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Bachère, Evelyne; Barranger, Audrey; Bruno, Roman; Rouxel, Julien; Menard, Dominique; Piquemal, David; Akcha, Farida

    2017-08-01

    One of the primary challenges in ecotoxicology is to contribute to the assessment of the ecological status of ecosystems. In this study, we used Pacific oyster Crassostrea gigas to explore the effects of a parental exposure to diuron, a herbicide frequently detected in marine coastal environments. The present toxicogenomic study provides evidence that exposure of oyster genitors to diuron during gametogenesis results in changes in offspring, namely, transcriptomic profile alterations, increased global DNA methylation levels and reduced growth and survival within the first year of life. Importantly, we highlighted the limitations to identify particular genes or gene expression signatures that could serve as biomarkers for parental herbicide-exposure and further for multigenerational and transgenerational effects of specific chemical stressors. By analyzing samples from two independent experiments, we demonstrated that, due to complex confounding effects with both tested solvent vehicles, diuron non-specifically affected the offspring transcriptome. These original results question the potential development of predictive genomic tools for detecting specific indirect impacts of contaminants in environmental risk assessments. However, our results indicate that chronic environmental exposure to diuron over several generations may have significant long term impacts on oyster populations with adverse health outcomes. Copyright © 2017. Published by Elsevier Inc.

  11. MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.

  12. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice.

    Directory of Open Access Journals (Sweden)

    Heather L Cameron

    Full Text Available Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil, or dieldrin (0.45, 2.25, and 4.5 microg/g body weight daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

  13. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    Science.gov (United States)

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. © 2016 The Author(s).

  14. Exposure of rainbow trout milt to mercury and cadmium alters sperm motility parameters and reproductive success

    International Nuclear Information System (INIS)

    Dietrich, Grzegorz J.; Dietrich, Mariola; Kowalski, R.K.; Dobosz, Stefan; Karol, Halina; Demianowicz, Wieslaw; Glogowski, Jan

    2010-01-01

    In the current work, seminal plasma was used for the first time as an incubation medium for monitoring short-time exposure effects of sublethal concentrations of mercury and cadmium ions on rainbow trout sperm. Sperm motility parameters (CASA) and hatching rates were used as gamete quality markers. Additionally live/dead sperm viability test and comet assay of DNA fragmentation were performed. We demonstrated that computer-assisted sperm motility analysis (CASA) may serve as a predictor of reproductive success, when milt contaminated with heavy metals is used. Results presented in this study demonstrate that mercury ions altered sperm motility characteristics at 1-10 mg Hg 2+ /l and 10 mg Cd 2+ /l and hatching rates at 10 mg Hg 2+ /l and 10 mg Cd 2+ /l after 4 h of exposure. Although mercury ions affected sperm motility parameters immediately after dilution with milt as well as at 4 h of exposure, no differences in sperm motility parameters were found between intact and mercury-treated milt after 24 h of exposure. Our results suggest that rainbow trout seminal plasma has a protective role against the toxic effects of mercury ions of rainbow trout sperm motility.

  15. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

    International Nuclear Information System (INIS)

    Meyer, Armando; Seidler, Frederic J.; Aldridge, Justin E.; Slotkin, Theodore A.

    2005-01-01

    Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a β-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: terbutaline on postnatal days (PN) 2-5 and CPF on PN11-14, with assessments conducted on PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), a transduction pathway shared by numerous neuronal and hormonal signals. Terbutaline altered signaling in the brainstem and cerebellum, with gender differences particularly notable in the cerebellum (enhanced AC in males, suppressed in females). By itself, CPF exposure elicited deficits in AC signaling in the midbrain, brainstem, and striatum. However, sequential exposure to terbutaline followed by CPF produced larger alterations and involved a wider spectrum of brain regions than were obtained with either agent alone. In the cerebral cortex, adverse effects of the combined treatment intensified between PN45 and PN60, suggesting that exposures alter the long-term program for development of synaptic communication, leading to alterations in AC signaling that emerge even after adolescence. These findings indicate that terbutaline, like CPF, is a developmental neurotoxicant, and reinforce the idea that its use in preterm labor may create a subpopulation that is sensitized to long-term CNS effects of organophosphorus insecticides

  16. Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus

    International Nuclear Information System (INIS)

    Guerrero Schimpf, Marlise; Milesi, María M.; Ingaramo, Paola I.; Luque, Enrique H.; Varayoud, Jorgelina

    2017-01-01

    Highlights: • Neonatal exposure to GBH lead to endometrial hyperplasia and increase proliferation. • GBH disrupts proteins involved in uterine organogenetic differentiation. • GBH exposure induced persistent increase of PR and Hoxa10 proteins. - Abstract: Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2 mg/kg) by sc injection every 48 h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic

  17. Association between lead exposure from electronic waste recycling and child temperament alterations.

    Science.gov (United States)

    Liu, Junxiao; Xu, Xijin; Wu, Kusheng; Piao, Zhongxian; Huang, Jinrong; Guo, Yongyong; Li, Weiqiu; Zhang, Yuling; Chen, Aimin; Huo, Xia

    2011-08-01

    We aimed to evaluate the dose-dependent effects of lead exposure on temperament alterations in children from a primitive e-waste (obsolete electrical and electronic devices) recycling area in Guiyu of China and a control area (Chendian, China). Blood lead levels (BLL) might be correlated with temperament, health, and relevant factors that were evaluated through Parent Temperament Questionnaire (PTQ), physical examination, and residential questionnaires. We collected venipuncture blood samples from 303 children (aged 3-7 years old) between January and February 2008. Child BLL were higher in Guiyu than in Chendian (median 13.2 μg/dL, range 4.0-48.5 μg/dL vs. 8.2 μg/dL, 0-21.3 μg/dL) (Pchildren (all Pchildren with low BLL (BLLchildren by increasing BLL and altering children temperament, although the exposure to other toxicants needs to be examined in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

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    Jill A. Poole

    2012-07-01

    Full Text Available Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE collected from a CAFO results in the activation of protein kinase C (PKC, elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6, and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF, tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability

  20. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

    Science.gov (United States)

    Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

    2017-05-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

  1. Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus

    International Nuclear Information System (INIS)

    Baranowska-Bosiacka, I.; Strużyńska, L.; Gutowska, I.; Machalińska, A.; Kolasa, A.; Kłos, P.; Czapski, G.A.; Kurzawski, M.; Prokopowicz, A.; Marchlewicz, M.

    2013-01-01

    Highlights: ► Pre- and neonatal Pb exposure decreased the number of hippocampal neurons. ► Lead caused ultrastructural alterations in CA1 region of hippocampus. ► Hippocampus is highly vulnerable to low level perinatal Pb exposure. ► Lead decreased BDNF level in the developing brain. ► Decreased Bax/Bcl2 ratio may protect hippocampus against Pb-induced apoptosis. -- Abstract: The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb) may intensify or inhibit apoptosis or necroptosis in the developing rat brain. Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring; the control group received distilled water. During the feeding of pups, mothers from the experimental group were still receiving PbAc. Pups were weaned at postnatal day 21 and the young rats of both groups then received only distilled water until postnatal day 28. This treatment protocol resulted in a concentration of Pb in rat offspring whole blood (Pb-B) below the threshold of 10 μg/dL, considered safe for humans.We studied Casp-3 activity and expression, AIF nuclear translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein expression as well as BDNF concentration in selected structures of the rat brain: forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic examinations showed alterations in hippocampal neurons.Our data shows that pre- and neonatal exposure of rats to Pb, leading to Pb-B below 10 μg/dL, can decrease the number of hippocampus neurons, occurring concomitantly with ultrastructural alterations in this region. We observed no morphological or molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF translocation to nucleus) in young brains, despite the reduced levels of BDNF. The potential protective factor against apoptosis was probably the decreased Bax/Bcl-2 ratio, which requires further investigation. Our

  2. Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood.

    Science.gov (United States)

    Solomon, Olivia; Yousefi, Paul; Huen, Karen; Gunier, Robert B; Escudero-Fung, Maria; Barcellos, Lisa F; Eskenazi, Brenda; Holland, Nina

    2017-07-01

    Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican-American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb-p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di-(2-ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398-410, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

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    Mariateresa Maldini

    2015-06-01

    Full Text Available The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle. We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the

  4. Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats.

    Science.gov (United States)

    Fernandez, Marina O; Bourguignon, Nadia S; Arocena, Paula; Rosa, Matías; Libertun, Carlos; Lux-Lantos, Victoria

    2018-03-15

    Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 μg 50 μl -1 oil (B500), or 50 μg 50 μl -1 (B50), or 5 μg 50 μl -1 (B5). Controls were injected with 50 μl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHβ and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E 2 increased basal TSH as well as prolactin release. On the other hand, both BPA and E 2 lowered the response to TRH. The results presented here show that the neonatal exposure to BPA alters the hypothalamic pituitary-thyroid axis in adult rats in estrus, possibly with effects on the pituitary and thyroid. They also show that BPA alters TSH release from rat PPC through direct actions on the pituitary. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Prenatal Cigarette Smoke Exposure Causes Hyperactivity and Agressive Behavior: Role of Altered Catcholamines and BDNF

    Science.gov (United States)

    Yochum, Carrie; Doherty-Lyon, Shannon; Hoffman, Carol; Hossain, Muhammad M.; Zellikoff, Judith T.; Richardson, Jason R.

    2014-01-01

    Smoking during pregnancy is associated with a variety of untoward effects on the offspring. However, recent epidemiological studies have brought into question whether the association between neurobehavioral deficits and maternal smoking is causal. We utilized an animal model of maternal smoking to determine the effects of prenatal cigarette smoke (CS) exposure on neurobehavioral development. Pregnant mice were exposed to either filtered air or mainstream CS from gestation day (GD) 4 to parturition for 4 hr/d and 5 d/wk, with each exposure producing maternal plasma concentration of cotinine equivalent to smoking <1 pack of cigarettes per day (25 ng/ml plasma cotinine level). Pups were weaned at postnatal day (PND) 21 and behavior assessed on at 4 weeks of age and again at 4–6 months of age. Male, but not female, offspring of CS-exposed dams demonstrated a significant increase in locomotor activity during adolescence and adulthood that was ameliorated by methylphenidate treatment. Additionally, male offspring exhibited increased aggression, as evidenced by decreased latency to attack and number of attacks in a resident intruder task. These behavioral abnormalities were accompanied by a significant decrease in striatal and cortical dopamine and serotonin and a significant reduction in brain-derived neurotrophic factor (BDNF) mRNA and protein. Taken in concert, these data demonstrate that prenatal exposure to CS produces behavioral alterations in mice that are similar to those observed in epidemiological studies linking maternal smoking to neurodevelopmental disorders and suggest a role for monoaminergic and BDNF alterations in these effects. PMID:24486851

  6. Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

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    Susanna L Lundström

    Full Text Available Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.Sixty-four oxylipins representing the cyclooxygenase (COX, lipoxygenase (LOX and cytochrome P450 (CYP metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS of bronchoalveolar lavage (BAL-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ. Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2 (PGE(2. Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

  7. Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

    Science.gov (United States)

    Lundström, Susanna L; Levänen, Bettina; Nording, Malin; Klepczynska-Nyström, Anna; Sköld, Magnus; Haeggström, Jesper Z; Grunewald, Johan; Svartengren, Magnus; Hammock, Bruce D; Larsson, Britt-Marie; Eklund, Anders; Wheelock, Åsa M; Wheelock, Craig E

    2011-01-01

    Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

  8. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones.

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    Po-Chin Huang

    Full Text Available Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy.We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, mono-(2-ethylhexyl phthalate (MEHP, mono-butyl phthalate (MnBP, of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4, free T4, and thyroid-binding globulin (TBG.Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%, MnBP (81% and MECPP (86%. Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97 in pregnant women using Bonferroni correction.We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

  9. Nighttime dim light exposure alters the responses of the circadian system.

    Science.gov (United States)

    Shuboni, D; Yan, L

    2010-11-10

    The daily light dark cycle is the most salient entraining factor for the circadian system. However, in modern society, darkness at night is vanishing as light pollution steadily increases. The impact of brighter nights on wild life ecology and human physiology is just now being recognized. In the present study, we tested the possible detrimental effects of dim light exposure on the regulation of circadian rhythms, using CD1 mice housed in light/dim light (LdimL, 300 lux:20 lux) or light/dark (LD, 300 lux:1 lux) conditions. We first examined the expression of clock genes in the suprachiasmatic nucleus (SCN), the locus of the principal brain clock, in the animals of the LD and LdimL groups. Under the entrained condition, there was no difference in PER1 peak expression between the two groups, but at the trough of the PER 1 rhythm, there was an increase in PER1 in the LdimL group, indicating a decrease in the amplitude of the PER1 rhythm. After a brief light exposure (30 min, 300 lux) at night, the light-induced expression of mPer1 and mPer2 genes was attenuated in the SCN of LdimL group. Next, we examined the behavioral rhythms by monitoring wheel-running activity to determine whether the altered responses in the SCN of LdimL group have behavioral consequence. Compared to the LD controls, the LdimL group showed increased daytime activity. After being released into constant darkness, the LdimL group displayed shorter free-running periods. Furthermore, following the light exposure, the phase shifting responses were smaller in the LdimL group. The results indicate that nighttime dim light exposure can cause functional changes of the circadian system, and suggest that altered circadian function could be one of the mechanisms underlying the adverse effects of light pollution on wild life ecology and human physiology. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Altered Parietal Activation during Non-symbolic Number Comparison in Children with Prenatal Alcohol Exposure

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    Keri J. Woods

    2018-01-01

    Full Text Available Number processing is a cognitive domain particularly sensitive to prenatal alcohol exposure, which relies on intact parietal functioning. Alcohol-related alterations in brain activation have been found in the parietal lobe during symbolic number processing. However, the effects of prenatal alcohol exposure on the neural correlates of non-symbolic number comparison and the numerical distance effect have not been investigated. Using functional magnetic resonance imaging (fMRI, we examined differences in brain activation associated with prenatal alcohol exposure in five parietal regions involved in number processing during a non-symbolic number comparison task with varying degrees of difficulty. fMRI results are presented for 27 Cape Colored children (6 fetal alcohol syndome (FAS/partial FAS, 5 heavily exposed (HE non-sydromal, 16 controls; mean age ± SD = 11.7 ± 1.1 years. Fetal alcohol exposure was assessed by interviewing mothers using a timeline follow-back approach. Separate subject analyses were performed in each of five regions of interest, bilateral horizontal intraparietal sulci (IPS, bilateral posterior superior parietal lobules (PSPL, and left angular gyrus (left AG, using the general linear model with predictors for number comparison and difficulty level. Mean percent signal change for each predictor was extracted for each subject for each region to examine group differences and associations with continuous measures of alcohol exposure. Although groups did not differ in performance, controls activated the right PSPL more during non-symbolic number comparison than exposed children, but this was not significant after controlling for maternal smoking, and the right IPS more than children with fetal alcohol syndrome (FAS or partial FAS. More heavily exposed children recruited the left AG to a greater extent as task difficulty increased, possibly to compensate, in part, for impairments in function in the PSPL and IPS. Notably, in non

  11. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Science.gov (United States)

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  12. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Directory of Open Access Journals (Sweden)

    Laurent Grégoire

    2018-01-01

    Full Text Available This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD and no abuse participants. We focused particularly on an early wave (C1/P1, the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology.

  13. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    International Nuclear Information System (INIS)

    Marlatt, Vicki L.; Veldhoen, Nik; Lo, Bonnie P.; Bakker, Dannika; Rehaume, Vicki; Vallée, Kurtis; Haberl, Maxine; Shang, Dayue; Aggelen, Graham C. van; Skirrow, Rachel C.; Elphick, James R.; Helbing, Caren C.

    2013-01-01

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26–28) tadpoles were immersed for 21 days in solvent control, 1.5 μg/L thyroxine (T 4 ), 0.3, 3 and 30 μg/L (nominal) TCS, or combined T 4 /TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T 4 treatment alone accelerated development concomitant with altered levels of TH receptors α and β, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 μg/L) was protective against tadpole mortality, this protection was lost in the presence of T 4 . The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  14. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    Energy Technology Data Exchange (ETDEWEB)

    Marlatt, Vicki L. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Veldhoen, Nik [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Lo, Bonnie P. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Bakker, Dannika; Rehaume, Vicki; Vallee, Kurtis [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Haberl, Maxine; Shang, Dayue; Aggelen, Graham C. van; Skirrow, Rachel C. [Pacific and Yukon Laboratory for Environmental Testing, Emergencies Operational Analytical Laboratories and Research Support Division, Environment Canada, 2645 Dollarton Highway, North Vancouver, B.C. V7H 1B1 (Canada); Elphick, James R. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Helbing, Caren C., E-mail: chelbing@uvic.ca [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada)

    2013-01-15

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26-28) tadpoles were immersed for 21 days in solvent control, 1.5 {mu}g/L thyroxine (T{sub 4}), 0.3, 3 and 30 {mu}g/L (nominal) TCS, or combined T{sub 4}/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T{sub 4} treatment alone accelerated development concomitant with altered levels of TH receptors {alpha} and {beta}, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 {mu}g/L) was protective against tadpole mortality, this protection was lost in the presence of T{sub 4}. The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  15. Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

    Science.gov (United States)

    Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

    2014-10-01

    Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. Copyright © 2014. Published by Elsevier Inc.

  16. In utero exposure to chloroquine alters sexual development in the male fetal rat

    International Nuclear Information System (INIS)

    Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

    2009-01-01

    Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

  17. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.

    Directory of Open Access Journals (Sweden)

    David A Davis

    Full Text Available Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM. In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3 or control filtered ambient air for 10 weeks (3×5 hour exposures per week, encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Does exposure to very high levels of natural radiation induce hematological alterations in humans?

    International Nuclear Information System (INIS)

    Ghiassi-Nejad, M.

    2003-01-01

    Full text: It has long been known that total body exposure to moderate doses decrease the number of circulating erythrocytes, platelets, granulocytes, and lymphocytes. However, data on hematopoietic effects of exposure to very low doses of ionizing radiation in humans are scarce. Recently it has been reported that hematological parameters have significant positive associations with the radiation dose received by residents lived near a nuclear power plant. Ramsar, a city in northern Iran, has some inhabited areas with the highest levels of natural radiation studied so far. A population of about 2000 is exposed to average annual radiation levels of 10.2 mGy y -1 and the highest recorded external gamma dose rates are about 130 mGy y -1 . In this study, hematological parameters such as counts of leukocytes, lymphocytes, monocytes, granulocytes, red blood cells, hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, PLT, and MPV were measured in the inhabitants. The results of this study indicated that there was no any statistically significant alteration in hematological parameters of the inhabitants of very high background radiation areas of Ramsar compared to those of a neighboring control area

  20. CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Megan K., E-mail: megan.horton@mssm.edu [Department of Preventive Medicine, Icahn School of Medicine, New York, New York (United States); Blount, Benjamin C.; Valentin-Blasini, Liza [National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia (United States); Wapner, Ronald [Department of Obstetrics and Gynecology, Columbia University, New York, New York (United States); Whyatt, Robin [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York (United States); Gennings, Chris [Department of Preventive Medicine, Icahn School of Medicine, New York, New York (United States); Factor-Litvak, Pam [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York (United States)

    2015-11-15

    Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood

  1. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in CD-1 mouse pups.

    Science.gov (United States)

    Venerosi, Aldina; Ricceri, Laura; Scattoni, Maria Luisa; Calamandrei, Gemma

    2009-03-30

    Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Late gestational exposure [gestational day (GD) 14-17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses. Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants.

  2. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    Directory of Open Access Journals (Sweden)

    Calamandrei Gemma

    2009-03-01

    Full Text Available Abstract Background Chlorpyrifos (CPF is a non-persistent organophosphate (OP largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [gestational day (GD 14–17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10. Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. Results As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking and explorative (wall rearing responses. Conclusion Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants.

  3. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

    Energy Technology Data Exchange (ETDEWEB)

    Coburn, C G [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E; Curras-Collazo, M [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)

    2004-09-15

    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  4. CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

    International Nuclear Information System (INIS)

    Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

    2015-01-01

    Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood

  5. Proteomic analysis revealed alterations of the Plasmodium falciparum metabolism following salicylhydroxamic acid exposure

    Directory of Open Access Journals (Sweden)

    Torrentino-Madamet M

    2011-09-01

    Full Text Available Marylin Torrentino-Madamet1, Lionel Almeras2, Christelle Travaillé1, Véronique Sinou1, Matthieu Pophillat3, Maya Belghazi4, Patrick Fourquet3, Yves Jammes5, Daniel Parzy11UMR-MD3, Université de la Méditerranée, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 2Unité de Recherche en Biologie et Epidémiologie Parasitaires, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 3Centre d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, 4Centre d'Analyse Protéomique de Marseille, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, 5UMR-MD2, Physiologie et Physiopathologie en Conditions d'Oxygénations Extrêmes, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, Marseille, FranceObjectives: Although human respiratory metabolism is characterized by the mitochondrial electron transport chain, some organisms present a “branched respiratory chain.” This branched pathway includes both a classical and an alternative respiratory chain. The latter involves an alternative oxidase. Though the Plasmodium falciparum alternative oxidase is not yet identified, a specific inhibitor of this enzyme, salicylhydroxamic acid (SHAM, showed a drug effect on P. falciparum respiratory function using oxygen consumption measurements. The present study aimed to highlight the metabolic pathways that are affected in P. falciparum following SHAM exposure.Design: A proteomic approach was used to analyze the P. falciparum proteome and determine the metabolic pathways altered following SHAM treatment. To evaluate the SHAM effect on parasite growth, the phenotypic alterations of P. falciparum after SHAM or/and hyperoxia exposure were observed.Results: After SHAM exposure, 26 proteins were significantly deregulated using a fluorescent two dimensional-differential gel electrophoresis. Among these deregulated proteins

  6. Exposure to dietary mercury alters cognition and behavior of zebra finches.

    Science.gov (United States)

    Swaddle, John P; Diehl, Tessa R; Taylor, Capwell E; Fanaee, Aaron S; Benson, Jessica L; Huckstep, Neil R; Cristol, Daniel A

    2017-04-01

    Environmental stressors can negatively affect avian cognitive abilities, potentially reducing fitness, for example by altering response to predators, display to mates, or memory of locations of food. We expand on current knowledge by investigating the effects of dietary mercury, a ubiquitous environmental pollutant and known neurotoxin, on avian cognition. Zebra finches Taeniopygia guttata were dosed for their entire lives with sub-lethal levels of mercury, at the environmentally relevant dose of 1.2 parts per million. In our first study, we compared the dosed birds with controls of the same age using tests of three cognitive abilities: spatial memory, inhibitory control, and color association. In the spatial memory assay, birds were tested on their ability to learn and remember the location of hidden food in their cage. The inhibitory control assay measured their ability to ignore visible but inaccessible food in favor of a learned behavior that provided the same reward. Finally, the color association task tested each bird's ability to associate a specific color with the presence of hidden food. Dietary mercury negatively affected spatial memory ability but not inhibitory control or color association. Our second study focused on three behavioral assays not tied to a specific skill or problem-solving: activity level, neophobia, and social dominance. Zebra finches exposed to dietary mercury throughout their lives were subordinate to, and more active than, control birds. We found no evidence that mercury exposure influenced our metric of neophobia. Together, these results suggest that sub-lethal exposure to environmental mercury selectively harms neurological pathways that control different cognitive abilities, with complex effects on behavior and fitness.

  7. Sucrose exposure in early life alters adult motivation and weight gain.

    Directory of Open Access Journals (Sweden)

    Cristianne R M Frazier

    2008-09-01

    Full Text Available The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  8. Sucrose exposure in early life alters adult motivation and weight gain.

    Science.gov (United States)

    Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A

    2008-09-17

    The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  9. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Bosco, Anthony; McKenna, Katherine L.; Carter, Kim W.; Elliot, John G.; Berry, Luke J.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2012-01-01

    Background: Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. Objectives: We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity. Methods: Pregnant BALB/c, C57BL/6, and C3H/HeARC mice were exposed to 0 (control) or 100 ?g/L...

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

    NARCIS (Netherlands)

    Boulle, F.; Pawluski, J.L.; Homberg, J.R.; Machiels, B.; Kroeze, Y.; Kumar, N.; Steinbusch, H.W.; Kenis, G.; Hove, D.L. van den

    2016-01-01

    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

  11. Alteration in expression of defence genes in Pisum sativum after exposure to supplementary ultraviolet-B radiation

    International Nuclear Information System (INIS)

    Strid, A.

    1993-01-01

    Alterations in the amounts of mRNA for different types of defence genes after exposure of peas to supplementary ultraviolet-B radiation are demonstrated. The expression of the genes which encode the chalcone synthase of the flavonoid biosynthetic pathway and glutathione reductase was induced, while a decrease was found for the chloroplastic radical-scavenging enzyme, superoxide dismutase. (author)

  12. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    Science.gov (United States)

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-12-12

    noticed in the cerebellum, while the expression of postsynaptic PSD-95 was significantly decreased in forebrain cortex and cerebellum, and raised in hippocampus. Additionally, we observed the lower level of BDNF in all brain structures in comparison to control animals. In conclusion, perinatal exposure to low doses of Pb caused pathological changes in nerve endings associated with the alterations in the level of key synaptic proteins. All these changes can lead to synaptic dysfunction, expressed by the impairment of the secretory mechanism and thereby to the abnormalities in neurotransmission as well as to the neuronal dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P.

    2004-01-01

    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

  14. Prenatal exposure to gamma/neutron irradiation: Sensorimotor alterations and paradoxical effects on learning

    International Nuclear Information System (INIS)

    Di Cicco, D.; Antal, S.; Ammassari-Teule, M.

    1991-01-01

    The effects of prenatal exposure on gamma/neutron radiations (0.5 Gy at about the 18th day of fetal life) were studied in a hybrid strain of mice (DBA/Cne males x C57BL/Cne females). During ontogeny, measurements of sensorimotor reflexes revealed in prenatally irradiated mice (1) a delay in sensorial development, (2) deficits in tests involving body motor control, and (3) a reduction of both motility and locomotor activity scores. In adulthood, the behaviour of prenatally irradiated and control mice was examined in the open field test and in reactivity to novelty. Moreover, their learning performance was compared in several situations. The results show that, in the open field test, only rearings were more frequent in irradiated mice. In the presence of a novel object, significant sex x treatment interactions were observed since ambulation and leaning against the novel object increased in irradiated females but decreased in irradiated males. Finally, when submitted to different learning tasks, irradiated mice were impaired in the radial maze, but paradoxically exhibited higher avoidance scores than control mice, possibly because of their low pain thresholds. Taken together, these observations indicate that late prenatal gamma/neutron irradiation induces long lasting alterations at the sensorimotor level which, in turn, can influence learning abilities of adult mice

  15. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    Science.gov (United States)

    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  16. Binge Toluene Exposure Alters Glutamate, Glutamine and GABA in the Adolescent Rat Brain as Measured by Proton Magnetic Resonance Spectroscopy*

    Science.gov (United States)

    Perrine, Shane A.; O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7 T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8,000 , or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either one or seven days later (on P35 or P42) to assess glutamate, glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced glutamate one day after exposure, with no effect on GABA, while after seven days, glutamate was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor glutamate was altered one day after exposure, whereas seven days after exposure, increases were observed in GABA and glutamate. Striatal glutamate and GABA levels measured after either one or seven days were not altered after toluene exposure. These findings show that one week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least one week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens. PMID:21126832

  17. Acute Exposure to Microcystin-Producing Cyanobacterium Microcystis aeruginosa Alters Adult Zebrafish (Danio rerio Swimming Performance Parameters

    Directory of Open Access Journals (Sweden)

    Luiza Wilges Kist

    2011-01-01

    Full Text Available Microcystins (MCs are toxins produced by cyanobacteria (blue-green algae, primarily Microcystis aeruginosa, forming water blooms worldwide. When an organism is exposed to environmental perturbations, alterations in normal behavioral patterns occur. Behavioral repertoire represents the consequence of a diversity of physiological and biochemical alterations. In this study, we assessed behavioral patterns and whole-body cortisol levels of adult zebrafish (Danio rerio exposed to cell culture of the microcystin-producing cyanobacterium M. aeruginosa (MC-LR, strain RST9501. MC-LR exposure (100 μg/L decreased by 63% the distance traveled and increased threefold the immobility time when compared to the control group. Interestingly, no significant alterations in the number of line crossings were found at the same MC-LR concentration and time of exposure. When animals were exposed to 50 and 100 μg/L, MC-LR promoted a significant increase (around 93% in the time spent in the bottom portion of the tank, suggesting an anxiogenic effect. The results also showed that none of the MC-LR concentrations tested promoted significant alterations in absolute turn angle, path efficiency, social behavior, or whole-body cortisol level. These findings indicate that behavior is susceptible to MC-LR exposure and provide evidence for a better understanding of the ecological consequences of toxic algal blooms.

  18. Bacillus subtilis alters the proportion of major membrane phospholipids in response to surfactin exposure.

    Science.gov (United States)

    Uttlová, Petra; Pinkas, Dominik; Bechyňková, Olga; Fišer, Radovan; Svobodová, Jaroslava; Seydlová, Gabriela

    2016-12-01

    Surfactin, an anionic lipopeptide produced by Bacillus subtilis, is an antimicrobial that targets the cytoplasmic membrane. Nowadays it appears increasingly apparent that the mechanism of resistance against these types of antibiotics consists of target site modification. This prompted us to investigate whether the surfactin non-producing strain B. subtilis 168 changes its membrane composition in response to a sublethal surfactin concentration. Here we show that the exposure of B. subtilis to surfactin at concentrations of 350 and 650 μg/ml (designated as SF350 and SF650, respectively) leads to a concentration-dependent growth arrest followed by regrowth with an altered growth rate. Analysis of the membrane lipid composition revealed modifications both in the polar head group and the fatty acid region. The presence of either surfactin concentration resulted in a reduction in the content of the major membrane phospholipid phosphatidylglycerol (PG) and increase in phosphatidylethanolamine (PE), which was accompanied by elevated levels of phosphatidic acid (PA) in SF350 cultures. The fatty acid analysis of SF350 cells showed a marked increase in non-branched high-melting fatty acids, which lowered the fluidity of the membrane interior measured as the steady-state fluorescence anisotropy of DPH. The liposome leakage of carboxyfluorescein-loaded vesicles resembling the phospholipid composition of surfactin-adapted cells showed that the susceptibility to surfactin-induced leakage is strongly reduced when the PG/PE ratio decreases and/or PA is included in the target bilayer. We concluded that the modifications of the phospholipid content of B. subtilis cells might provide a self-tolerance of the membrane active surfactin. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures.

    Science.gov (United States)

    Kakumanu, Madhavi L; Reeves, Alison M; Anderson, Troy D; Rodrigues, Richard R; Williams, Mark A

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2-V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation.

  20. Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

    International Nuclear Information System (INIS)

    Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

    2003-01-01

    Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G 4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

  1. Adolescent fluoxetine exposure produces enduring, sex-specific alterations of visual discrimination and attention in rats.

    Science.gov (United States)

    LaRoche, Ronee B; Morgan, Russell E

    2007-01-01

    Over the past two decades the use of selective serotonin reuptake inhibitors (SSRIs) to treat behavioral disorders in children has grown rapidly, despite little evidence regarding the safety and efficacy of these drugs for use in children. Utilizing a rat model, this study investigated whether post-weaning exposure to a prototype SSRI, fluoxetine (FLX), influenced performance on visual tasks designed to measure discrimination learning, sustained attention, inhibitory control, and reaction time. Additionally, sex differences in response to varying doses of fluoxetine were examined. In Experiment 1, female rats were administered (P.O.) fluoxetine (10 mg/kg ) or vehicle (apple juice) from PND 25 thru PND 49. After a 14 day washout period, subjects were trained to perform a simultaneous visual discrimination task. Subjects were then tested for 20 sessions on a visual attention task that consisted of varied stimulus delays (0, 3, 6, or 9 s) and cue durations (200, 400, or 700 ms). In Experiment 2, both male and female Long-Evans rats (24 F, 24 M) were administered fluoxetine (0, 5, 10, or 15 mg/kg) then tested in the same visual tasks used in Experiment 1, with the addition of open-field and elevated plus-maze testing. Few FLX-related differences were seen in the visual discrimination, open field, or plus-maze tasks. However, results from the visual attention task indicated a dose-dependent reduction in the performance of fluoxetine-treated males, whereas fluoxetine-treated females tended to improve over baseline. These findings indicate that enduring, behaviorally-relevant alterations of the CNS can occur following pharmacological manipulation of the serotonin system during postnatal development.

  2. Environmental tobacco smoke exposure and EGFR and ALK alterations in never smokers' lung cancer. Results from the LCRINS study.

    Science.gov (United States)

    Torres-Durán, María; Ruano-Ravina, Alberto; Kelsey, Karl T; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Abdulkader, Ihab; Provencio, Mariano; Abal-Arca, José; Castro-Añón, Olalla; Montero-Martínez, Carmen; Vidal-García, Iria; Amenedo, Margarita; Golpe-Gómez, Antonio; Martínez, Cristina; Guzmán-Taveras, Rosirys; Mejuto-Martí, María José; Fernández-Villar, Alberto; Barros-Dios, Juan Miguel

    2017-12-28

    Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant. Exposure during adulthood, at home or at workplace, did not show any association with EGFR mutation. The mutation type L858R seemed the most associated with a lower probability of EGFR alterations for ETS exposure at home in adult life. There is no apparent association between ETS exposure and ALK translocation. These results might suggest that ETS exposure during childhood or at home in adult life could influence the EGFR mutations profile in lung cancer in never smokers, reducing the probability of presenting EFGR mutation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2008-02-01

    Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  4. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Science.gov (United States)

    Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

    2008-01-01

    Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience. PMID:18301720

  5. Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

    Directory of Open Access Journals (Sweden)

    Leavell Sarah

    2010-05-01

    Full Text Available Abstract Background Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control and then cats were vaginally challenged with cell-associated or cell-free FIV. Results Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. Conclusions The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus can be modulated by mucosal exposure to uninfected heterologous cells.

  6. Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

    Science.gov (United States)

    Chao, Linda L; Raymond, Morgan R; Leo, Cynthia K; Abadjian, Linda R

    2017-10-01

    To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

  7. Alterations in prostacyclin and thromboxane formation by chronic cigarette smoke exposure: temporal relationships and whole smoke vs. gas phase

    Energy Technology Data Exchange (ETDEWEB)

    Lubawy, W.C.; Culpepper, B.T.; Valentovic, M.A.

    1986-04-01

    Chronic cigarette smoke exposure in vivo causes decreased conversion of (/sup 14/C)arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGI2/TXA2 balance may be part of the mechanism through which smoking increases the risk of cardiovascular disease. To study the influence of smoke exposure duration on this response, male rats were exposed daily to 10 puffs of freshly generated cigarette smoke. Animals were killed after 1, 4, 14, 28 and 57 days of smoke exposure and 3, 7, 14 and 28 days after cessation of the 57-day of smoke-exposure regimen. Elevated carboxyhemoglobin levels during the smoke-exposure sessions verified smoke (gas phase) inhalation. Statistically significant alterations in prostacyclin synthesis preceded those of thromboxane. A decrease of 20-25% (P less than 0.05) in PGI2 production from (/sup 14/C)AA in isolated aortic tissue was found beginning 28 days after smoke was initiated and quickly rebounded when smoke exposure was terminated. Increased production of TXA2 from (/sup 14/C)AA by isolated platelets became statistically significant (P less than 0.05) on the 57th day and returned to normal 7-14 days after cessation of smoke exposure. To determine the effect of gas phase constituents on the PGI2/TXA2 balance a second series of experiments divided male and female Sprague-Dawley rats into sham, whole smoke and gas phase groups. Gas phase was produced by passing whole smoke through a Cambridge filter to remove particulate matter. Per cent COHb averaged 1.4 for sham, 7.8 for whole smoke and 9.4 for gas phase groups.

  8. Associations between personal exposures to VOCs and alterations in cardiovascular physiology: Detroit Exposure and Aerosol Research Study (DEARS) - presentation

    Science.gov (United States)

    Introduction: An adult cohort consisting of 63 participants engaged in the US EPA’s recent Detroit Exposure and Aerosol Research Study (DEARS) and a University of Michigan cardiovascular sub-study conducted during summer and winter periods over 3 years between 2004 and 2007...

  9. Associations between Personal Exposures to VOCs and Alterations in Cardiovascular Physiology: Detroit Exposure and Aerosol Research Study (DEARS)

    Science.gov (United States)

    Background: An adult cohort consisting of 63 participants engaged in the US EPA’s recent Detroit Exposure and Aerosol Research Study (DEARS) and a University of Michigan cardiovascular sub-study conducted during summer and winter periods over 3 years between 2004 and 2007 (5 seas...

  10. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Directory of Open Access Journals (Sweden)

    Marjo J. den Broeder

    2017-04-01

    Full Text Available Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio. We used label-free Stimulated Raman Scattering (SRS microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf and compared standard feed conditions (StF to a high fat diet (HFD or high glucose diet (HGD. We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM or Tris(1,3-dichloroisopropylphosphate (TDCiPP, 0.5 µM from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo.

  11. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Science.gov (United States)

    den Broeder, Marjo J.; Moester, Miriam J. B.; Kamstra, Jorke H.; Cenijn, Peter H.; Davidoiu, Valentina; Kamminga, Leonie M.; Ariese, Freek; de Boer, Johannes F.; Legler, Juliette

    2017-01-01

    Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo. PMID:28441764

  12. Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness

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    Lichtman Aron H

    2011-01-01

    Full Text Available Abstract Background Previously we have found that cannabinoid treatment of zebra finches during sensorimotor stages of vocal development alters song patterns produced in adulthood. Such persistently altered behavior must be attributable to changes in physiological substrates responsible for song. We are currently working to identify the nature of such physiological changes, and to understand how they contribute to altered vocal learning. One possibility is that developmental agonist exposure results in altered expression of elements of endocannabinoid signaling systems. To test this hypothesis we have studied effects of the potent cannabinoid receptor agonist WIN55212-2 (WIN on endocannabinoid levels and densities of CB1 immunostaining in zebra finch brain. Results We found that late postnatal WIN treatment caused a long-term global disregulation of both levels of the endocannabinoid, 2-arachidonyl glycerol (2-AG and densities of CB1 immunostaining across brain regions, while repeated cannabinoid treatment in adults produced few long-term changes in the endogenous cannabinoid system. Conclusions Our findings indicate that the zebra finch endocannabinoid system is particularly sensitive to exogenous agonist exposure during the critical period of song learning and provide insight into susceptible brain areas.

  13. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    Science.gov (United States)

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  14. Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells

    DEFF Research Database (Denmark)

    Jantzen, Kim; Møller, Peter Horn; Karottki, Dorina Gabriela

    2016-01-01

    . Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate......Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked...... to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related...

  15. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Directory of Open Access Journals (Sweden)

    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  16. Acrolein inhalation alters myocardial synchrony and performance at and below exposure concentrations that cause ventilatory responses

    Science.gov (United States)

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we ...

  17. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    Science.gov (United States)

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  18. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

    Directory of Open Access Journals (Sweden)

    Eugen Dhimolea

    Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

  19. Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

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    Golam Mohammod Mostakim

    2015-01-01

    Full Text Available Quinalphos (QP is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p<0.05 at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations.

  20. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

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    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  1. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

    OpenAIRE

    Balsevich, G.; Baumann, V.; Uribe, A.; Chen, A.; Schmidt, M.

    2016-01-01

    Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. Methods: We used a mouse...

  2. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

    Science.gov (United States)

    Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

  3. Exposure of mice to cigarette smoke and/or light causes DNA alterations in heart and aorta

    International Nuclear Information System (INIS)

    Izzotti, Alberto; D'Agostini, Francesco; Balansky, Roumen; Degan, Paolo; Pennisi, Tanya M.; Steele, Vernon E.; De Flora, Silvio

    2008-01-01

    Cigarette smoke (CS) is a major risk factor for cardiovascular diseases, cancer, and other chronic degenerative diseases. UV-containing light is the most ubiquitous DNA-damaging agent existing in nature, but its possible role in cardiovascular diseases had never been suspected before, although it is known that mortality for cardiovascular diseases is increased during periods with high temperature and solar irradiation. We evaluated whether exposure of Swiss CD-1 mice to environmental CS (ECS) and UV-C-covered halogen quartz lamps, either individually or in combination, can cause DNA damage in heart and aorta cells. Nucleotide alterations were evaluated by 32 P postlabeling methods and by HPLC-electrochemical detection. The whole-body exposure of mice to ECS considerably increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and of bulky DNA adducts in both heart and aorta. Surprisingly, even exposure to a light that simulated solar irradiation induced oxidatively generated damage in both tissues. The genotoxic effects of UV light in internal organs is tentatively amenable to formation of unidentified long-lived mutagenic products in the skin of irradiated mice. Nucleotide alterations were even more pronounced when the mice were exposed to smoke and/or light during the first 5 weeks of life rather than during adulthood for an equivalent period of time. Although the pathogenetic meaning is uncertain, DNA damage in heart and aorta may tentatively be related to cardiomyopathies and to the atherogenesis process, respectively

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Histopathological Alterations of Hybrid Walking Catfish (Clarias macrocephalus x Clarias gariepinus in Acute and Subacute Cadmium Exposure

    Directory of Open Access Journals (Sweden)

    Nuntiya Pantung

    2008-01-01

    Full Text Available Histopathological alterations occur in the gills, livers and kidneys of 3-month old hybrid walking catsfich (Clarias macrocephalus x Clarias gariepinos after acute and subacute cadmium exposure in water, and after intraperitoneal injection.The 96-h LC50 for cadmium in recirculation open systems was 13.6 mg/l, and the 96-h LD50 1.6 mg/kg of fish. Light microscopic studies were carried out in gills, livers and kidneys. Gill alterations included an increased number of chloride cells, breakdown of the pillar cells and edema of the epithelial cells. In the liver there was blood conjestion in sinusoids and swelling of hepatocytes. The kidneys showed vacuolation and necrosis of proximal tubular cells.

  6. High psychosis liability is associated with altered autonomic balance during exposure to Virtual Reality social stressors

    NARCIS (Netherlands)

    Counotte, Jacqueline; Pot-Kolder, Roos; van Roon, Arie M.; Hoskam, Olivier; van der Gaag, Mark; Veling, Wim

    Background: Social stressors are associated with an increased risk of psychosis. Stress sensitisation is thought to be an underlying mechanismand may be reflected in an altered autonomic stress response. Using an experimental Virtual Reality design, the autonomic stress response to social

  7. Secretion of Interferon gamma (IFNγ) from Human Immune Cells is Altered by Exposure to Tributyltin (TBT) and Dibutyltin (DBT)

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2013-01-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and also alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 μM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from NK cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. PMID:24357260

  8. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study

    Directory of Open Access Journals (Sweden)

    Rafati A.

    2015-09-01

    Full Text Available Introduction: The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog’s isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz. Materials and Methods: Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF radiation emitted from a common Jammer at a distance of 1m from the jammer’s antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T, the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz as stimuli. Results: The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. Conclusion: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

  9. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study.

    Science.gov (United States)

    Rafati, A; Rahimi, S; Talebi, A; Soleimani, A; Haghani, M; Mortazavi, S M J

    2015-09-01

    The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer's antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

  10. Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

    Directory of Open Access Journals (Sweden)

    Danielle Botelho

    2018-03-01

    Full Text Available Here we examine the organ level toxicology of both carbon black (CB and silver nanoparticles (AgNP. We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF. C57Bl6/J male mice were intratracheally instilled with saline (control, low (0.05 μg/g or high (0.5 μg/g doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

  11. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

    Directory of Open Access Journals (Sweden)

    Abdelhalim Mohamed

    2012-01-01

    Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

  12. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/β-catenin signaling in the thymus resulting in altered thymocyte development

    International Nuclear Information System (INIS)

    Hanson, Miranda L.; Brundage, Kathleen M.; Schafer, Rosana; Tou, Janet C.; Barnett, John B.

    2010-01-01

    Cadmium (Cd) is both an environmental pollutant and a component of cigarette smoke. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/β-catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. This study was designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/β-catenin pathways. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose (10 ppm) of Cd throughout pregnancy and effects on the thymus were assessed on the day of birth. Thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways were assessed using real-time RT-PCR and western blot, respectively. Prenatal Cd exposure increased the number of CD4 + cells and a subpopulation of double-negative cells (DN; CD4 - CD8 - ), DN4 (CD44 - CD25 - ). Shh and Wnt/β-catenin signaling were both decreased in the thymus. Target genes of Shh (Patched1 and Gli1) and Wnt/β-catenin (c-fos, and c-myc) were affected differentially among thymocyte subpopulations. These findings suggest that prenatal exposure to Cd dysregulates two signaling pathways in the thymus, resulting in altered thymocyte development.

  13. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths

    Directory of Open Access Journals (Sweden)

    Herr Caroline EW

    2010-08-01

    Full Text Available Abstract Background Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month. Methods Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+, B lymphocytes (CD19+ and natural killer (NK cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH and particulate matter 2.5 were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births. Results The adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation. Conclusions PAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.

  14. OXIDATIVE STRESS-DEPENDENT ALTERED IMMUNE RESPONSES AND CELL DEATH IN SUBSTANTIA NIGRA AFTER OZONE EXPOSURE IN RAT

    Directory of Open Access Journals (Sweden)

    Selva eRivas - Arancibia

    2015-05-01

    Full Text Available Parkinson’s disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent 1 spectrophotometric analysis for protein oxidation; 2 western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and 3 immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson’s disease.

  15. Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior.

    Science.gov (United States)

    Scully, C M; Estill, C T; Amodei, R; McKune, A; Gribbin, K P; Meaker, M; Stormshak, F; Roselli, C E

    2018-01-01

    Prenatal androgens are largely responsible for growth and differentiation of the genital tract and testis and for organization of the control mechanisms regulating male reproductive physiology and behavior. The aim of the present study was to evaluate the impact of inappropriate exposure to excess testosterone (T) during the first trimester of fetal development on the reproductive function, sexual behavior, and fertility potential of rams. We found that biweekly maternal T propionate (100 mg) treatment administered from Day 30-58 of gestation significantly decreased (P < 0.05) postpubertal scrotal circumference and sperm concentration. Prenatal T exposure did not alter ejaculate volume, sperm motility and morphology or testis morphology. There was, however, a trend for more T-exposed rams than controls to be classified as unsatisfactory potential breeders during breeding soundness examinations. Postnatal serum T concentrations were not affected by prenatal T exposure, nor was the expression of key testicular genes essential for spermatogenesis and steroidogenesis. Basal serum LH did not differ between treatment groups, nor did pituitary responsiveness to GnRH. T-exposed rams, like control males, exhibited vigorous libido and were sexually attracted to estrous females. In summary, these results suggest that exposure to exogenous T during the first trimester of gestation can negatively impact spermatogenesis and compromise the reproductive fitness of rams. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Neuroprotective Effect of Ginseng against Alteration of Calcium Binding Proteins Immunoreactivity in the Mice Hippocampus after Radiofrequency Exposure

    Directory of Open Access Journals (Sweden)

    Dhiraj Maskey

    2013-01-01

    Full Text Available Calcium binding proteins (CaBPs such as calbindin D28-k, parvalbumin, and calretinin are able to bind Ca2+ with high affinity. Changes in Ca2+ concentrations via CaBPs can disturb Ca2+ homeostasis. Brain damage can be induced by the prolonged electromagnetic field (EMF exposure with loss of interacellular Ca2+ balance. The present study investigated the radioprotective effect of ginseng in regard to CaBPs immunoreactivity (IR in the hippocampus through immunohistochemistry after one-month exposure at 1.6 SAR value by comparing sham control with exposed and ginseng-treated exposed groups separately. Loss of dendritic arborization was noted with the CaBPs in the Cornu Ammonis areas as well as a decrease of staining intensity of the granule cells in the dentate gyrus after exposure while no loss was observed in the ginseng-treated group. A significant difference in the relative mean density was noted between control and exposed groups but was nonsignificant in the ginseng-treated group. Decrease in CaBP IR with changes in the neuronal staining as observed in the exposed group would affect the hippocampal trisynaptic circuit by alteration of the Ca2+ concentration which could be prevented by ginseng. Hence, ginseng could contribute as a radioprotective agent against EMF exposure, contributing to the maintenance of Ca2+ homeostasis by preventing impairment of intracellular Ca2+ levels in the hippocampus.

  17. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE PERMANENTLY ALTERS REPRODUCTIVE COMPETENCE IN THE CD-1 MOUSE

    Science.gov (United States)

    While the adult mouse Leydig cell (LC) has been considered refractory to cytotoxic destruction by ethane dimethanesulfonate (EDS), the potential consequences of exposure during reproductive development in this species are unknown. Herein pregnant CD-1 mice were treated with 160 m...

  18. Exposure of fluid milk to LED light negatively affects consumer perception and alters underlying sensory properties.

    Science.gov (United States)

    Martin, Nicole; Carey, Nancy; Murphy, Steven; Kent, David; Bang, Jae; Stubbs, Tim; Wiedmann, Martin; Dando, Robin

    2016-06-01

    Fluid milk consumption per capita in the United States has been steadily declining since the 1940s. Many factors have contributed to this decline, including the increasing consumption of carbonated beverages and bottled water. To meet the challenge of stemming the decline in consumption of fluid milk, the dairy industry must take a systematic approach to identifying and correcting for factors that negatively affect consumers' perception of fluid milk quality. To that end, samples of fluid milk were evaluated to identify factors, with a particular focus on light-emitting diode (LED) light exposure, which negatively affect the perceived sensory quality of milk, and to quantify their relative effect on the consumer's experience. Fluid milk samples were sourced from 3 processing facilities with varying microbial postprocessing contamination patterns based on historical testing. The effect of fat content, light exposure, age, and microbiological content were assayed across 23 samples of fluid milk, via consumer, descriptive sensory, and instrumental analyses. Most notably, light exposure resulted in a broad negative reaction from consumers, more so than samples with microbiological contamination exceeding 20,000 cfu/mL on days approaching code. The predominant implication of the study is that a component of paramount importance in ensuring the success of the dairy industry would be to protect fluid milk from all sources of light exposure, from processing plant to consumer. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. C60 exposure induced tissue damage and gene expression alterations in the earthworm Lumbricus rubellus

    NARCIS (Netherlands)

    Ploeg, van der M.J.C.; Handy, R.D.; Heckmann, L.H.; Hout, van der A.; Brink, van den N.W.

    2013-01-01

    Effects of C60 exposure (0, 15 or 154 mg/kg soil) on the earthworm Lumbricus rubellus were assessed at the tissue and molecular level, in two experiments. In the first experiment, earthworms were exposed for four weeks, and in the second lifelong. In both experiments, gene expression of heat shock

  20. Serum vitamin D levels are not altered after controlled diesel exhaust exposures in healthy human subjects

    Science.gov (United States)

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; ...

  1. Alterations in microbiota structure and neurobehavior in zebrafish following developmental exposure to estrogenic compounds

    Science.gov (United States)

    Exposure to Bisphenol A (BPA), a high-production volume chemical and widespread environmental contaminant, has been associated with adverse endocrine and neurodevelopmental effects. Growing public concern over the safety of BPA has resulted in swift replacement with a suite of al...

  2. Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets

    NARCIS (Netherlands)

    Lan, Qing; Vermeulen, Roel; Dai, Yufei; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Bin, Ping; Kim, Christopher; Bassig, Bryan A; Hosgood, H Dean; Silverman, Debra; Zheng, Yuxin; Rothman, Nathaniel

    2015-01-01

    BACKGROUND: The International Agency for Research on Cancer recently classified diesel engine exhaust (DEE) as a Group I carcinogen based largely on its association with lung cancer. However, the exposure-response relationship is still a subject of debate and the underlying mechanism by which DEE

  3. Alteration of cellular immune responses in the seastar Asterias rubens following dietary exposure to cadmium

    International Nuclear Information System (INIS)

    Coteur, G.; Gillan, D.; Pernet, Ph.; Dubois, Ph.

    2005-01-01

    Several parameters of cellular immunity in seastars fed Cd-contaminated mussels were analyzed. The accumulation of cadmium in the seastars did not alter the concentration of amoebocytes in the coelomic fluid. On the contrary, the immune cells showed a reduced phagocytic activity and an increased production of reactive oxygen species. These effects may lead to an inability of the seastars to cope with bacterial infections and to oxidative damages to self tissue that could threaten the survival of the animals

  4. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  5. Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain.

    Science.gov (United States)

    Ijomone, Omamuyovwi Meashack; Okori, Stephen Odey; Ijomone, Olayemi Kafilat; Ebokaiwe, Azubike Peter

    2018-02-26

    Nickel (Ni) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for neurological symptoms in humans. The present study investigated the behavior and histomorphological alterations in brain of rats sub-acutely exposed to nickel chloride (NiCl 2 ) and the possible involvement of oxidative stress. Rats were administered with 5, 10 or 20 mg/kg NiCl 2 via intraperitoneal injections for 21 days. Neurobehavioral assessment was performed using the Y-maze and open field test (OFT). Histomorphological analyses of brain tissues, as well as biochemical determination of oxidative stress levels were performed. Results showed that Ni treatments significantly reduced body weight and food intake. Cognitive and motor behaviors on the Y-maze and OFT, respectively, were compromised following Ni treatments. Administration of Ni affected neuronal morphology in the brain and significantly reduced percentage of intact neurons in both hippocampus and striatum. Additionally, markers of oxidative stress levels and nitric oxide (NO) levels were significantly altered following Ni treatments. These data suggest that compromised behavior and brain histomorphology following Ni exposures is associated with increase in oxidative stress.

  6. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse

    Directory of Open Access Journals (Sweden)

    Umezawa Masakazu

    2009-07-01

    Full Text Available Abstract Background Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2 on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO and Medical Subject Headings (MeSH terms information. Results Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. Conclusion Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system.

  7. Does prenatal exposure to vitamin D-fortified margarine and milk alter birth weight?

    DEFF Research Database (Denmark)

    Jensen, Camilla B; Berentzen, Tina L; Gamborg, Michael

    2014-01-01

    The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention with mandat......The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention...... the initiation and termination of vitamin D fortification programmes. In total, four sets of analyses were performed. Information on birth weight was available in the Copenhagen School Health Record Register for all school children in Copenhagen. The mean birth weight was lower among the exposed than non...

  8. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

    OpenAIRE

    Ciss?, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

    2017-01-01

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to eit...

  9. Long term impairment of cognitive functions and alterations of NMDAR subunits after continuous microwave exposure.

    Science.gov (United States)

    Wang, Hui; Tan, Shengzhi; Xu, Xinping; Zhao, Li; Zhang, Jing; Yao, Binwei; Gao, Yabing; Zhou, Hongmei; Peng, Ruiyun

    2017-11-01

    The long term effects of continuous microwave exposure cannot be ignored for the simulation of the real environment and increasing concerns about the negative cognitive effects of microwave exposure. In this study, 220 male Wistar rats were exposed by a 2.856GHz radiation source with the average power density of 0, 2.5, 5 and 10mW/cm 2 for 6min/day, 5days/week and up to 6weeks. The MWM task, the EEG analysis, the hippocampus structure observation and the western blot were applied until the 12months after microwave exposure to detect the spatial learning and memory abilities, the cortical electrical activity, changes of hippocampal structure and the NMDAR subunits expressions. Results found that the rats in the 10mW/cm 2 group showed the decline of spatial learning and memory abilities and EEG disorders (the decrease of EEG frequencies, and increase of EEG amplitudes and delta wave powers). Moreover, changes of basic structure and ultrastructure of hippocampus also found in the 10 and 5mW/cm 2 groups. The decrease of NR 2A, 2B and p-NR2B might contribute to the impairment of cognitive functions. Our findings suggested that the continuous microwave exposure could cause the dose-dependent long term impairment of spatial learning and memory, the abnormalities of EEG and the hippocampal structure injuries. The decrease of NMDAR key subunits and phosphorylation of NR 2B might contribute to the cognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides

    Science.gov (United States)

    2016-01-13

    hormone bindi Bdnf BDNF Brain-derived neurotrophic factor Mdk MDK Midkine (neurite growth -promoting fa Rbp4 RBP4 Retinol binding protein 4, plasma...cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits ), but the biological mechanism(s...neurobehavioral deficits following subchronic exposure to CPF at a level that inhibits hippocampal cholinesterase to less than 20% of control. An equally

  11. Traffic pollution exposure is associated with altered brain connectivity in school children.

    Science.gov (United States)

    Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells

    Directory of Open Access Journals (Sweden)

    Yan Yin

    2012-11-01

    Developmental exposure to diethylstilbestrol (DES causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of peroxisome proliferator-activated receptor-γ (PPARγ-mediated adipogenesis and lipid metabolism, including PPARγ itself, are targets of DES in the neonatal uterus. Transmission electron microscopy and Oil-Red O staining further demonstrate a dramatic increase in lipid deposition in uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor-induced reproductive abnormalities.

  13. Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture.

    Science.gov (United States)

    Lima, Florence; Swift, Joshua M; Greene, Elisabeth S; Allen, Matthew R; Cunningham, David A; Braby, Leslie A; Bloomfield, Susan A

    2017-10-01

    Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

  14. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

    Science.gov (United States)

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

  15. Alteration of gene expression in MDA-MB-453 breast cancer cell line in response to continuous exposure to Trastuzumab.

    Science.gov (United States)

    Sharieh, Elham Abu; Awidi, Abdulla S; Ahram, Mamoun; Zihlif, Malek A

    2016-01-10

    Development of resistance against cancer therapeutic agents is a common problem in cancer management. Trastuzumab resistance is one of the challenges in management of HER-2-positive breast cancer patients resulting in breast cancer progression, metastasis, and patient poor outcome. The aim of this study is to determine the alteration in gene expression in response to Trastuzumab resistance after long-term exposure to Trastuzumab. The Trastuzumab-resistant MDA-MB-453 (MDA-MB-453/TR) cell line was developed by exposing cells to 10 μM Trastuzumab continuously for 6 months. Sensitivity toward Trastuzumab was tested using cell viability assays. The acquisition of an epithelial-to mesenchymal transition (EMT) phenotype was also observed in parallel with the development of resistance. Based on the real-time-based PCR array technology, several genes were altered affecting multiple networks. The most up-regulated genes were TGF-β1 and EGF, and IGFBP-3. These genes are known to have a critical role in Trastuzumab resistance in breast cancer cell lines and/or in the acquisition of EMT. They are also recognized for their role in cancer progression and metastasis. These alterations indicate that the development of Trastuzumab resistance is multifactorial and involves a development of a mesenchymal like phenotype. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

    Directory of Open Access Journals (Sweden)

    Heather A Enright

    Full Text Available Triclocarban (TCC is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS. 14C-TCC (100 nM was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

  17. Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

    Science.gov (United States)

    Enright, Heather A; Falso, Miranda J S; Malfatti, Michael A; Lao, Victoria; Kuhn, Edward A; Hum, Nicholas; Shi, Yilan; Sales, Ana Paula; Haack, Kurt W; Kulp, Kristen S; Buchholz, Bruce A; Loots, Gabriela G; Bench, Graham; Turteltaub, Kenneth W

    2017-01-01

    Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

  18. Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance.

    Science.gov (United States)

    Gibson, D L; Gill, S K; Brown, K; Tasnim, N; Ghosh, S; Innis, S; Jacobson, K

    2015-01-01

    Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

  19. The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Spinetta, Michael J; Thomas, Jennifer D; Riley, Edward P

    2011-01-01

    The third trimester in human fetal development represents a critical time of brain maturation referred to as the "brain growth spurt". This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats. On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning. Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure. These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Alteration of the Carbon and Nitrogen Isotopic Composition in the Martian Surface Rocks Due to Cosmic Ray Exposure

    Science.gov (United States)

    Pavlov, A. A.; Pavlov, A. K.; Ostryakov, V. M.; Vasilyev, G. I.; Mahaffy, P.; Steele, A.

    2014-01-01

    C-13/C-12 and N-15/N-14 isotopic ratios are pivotal for our understanding of the Martian carbon cycle, history of the Martian atmospheric escape, and origin of the organic compounds on Mars. Here we demonstrate that the carbon and nitrogen isotopic composition of the surface rocks on Mars can be significantly altered by the continuous exposure of Martian surface to cosmic rays. Cosmic rays can effectively produce C-13 and N-15 isotopes via spallation nuclear reactions on oxygen atoms in various Martian rocks. We calculate that in the top meter of the Martian rocks, the rates of production of both C-13 and N-15 due to galactic cosmic rays (GCRs) exposure can vary within 1.5-6 atoms/cm3/s depending on rocks' depth and chemical composition. We also find that the average solar cosmic rays can produce carbon and nitrogen isotopes at a rate comparable to GCRs in the top 5-10 cm of the Martian rocks. We demonstrate that if the total carbon content in a surface Martian rock is <10 ppm, then the "light," potentially "biological" C-13/C-12 ratio would be effectively erased by cosmic rays over 3.5 billion years of exposure. We found that for the rocks with relatively short exposure ages (e.g., 100 million years), cosmogenic changes in N-15/N-14 ratio are still very significant. We also show that a short exposure to cosmic rays of Allan Hills 84001 while on Mars can explain its high-temperature heavy nitrogen isotopic composition (N-15/N-14). Applications to Martian meteorites and the current Mars Science Laboratory mission are discussed.

  1. Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring

    International Nuclear Information System (INIS)

    Lundberg, Rebecca; Lyche, Jan L.; Ropstad, Erik; Aleksandersen, Mona; Roenn, Monika; Skaare, Janneche U.; Larsson, Sune; Orberg, Jan; Lind, P. Monica

    2006-01-01

    The aim of this study was to investigate if environmentally relevant doses of the putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused changes in bone tissue in female goat offspring following perinatal exposure. Goat dams were orally dosed with PCB 153 in corn oil (98 μg/kg body wt/day) or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The offspring were exposed to PCB in utero and through mother's milk. The suckling period lasted for 6 weeks. Offspring metacarpal bones were analysed using peripheral quantitative computed tomography (pQCT) after euthanisation at 9 months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of the total bone length, and the metaphyseal bone at a distance of 9%. Also, biomechanical three-point bending of the bones was conducted, with the load being applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure significantly decreased the total cross-sectional area (125 mm 2 ± 4) versus non-exposed (142 mm 2 ± 5), decreased the marrow cavity (38 mm 2 ± 4) versus non-exposed (50 mm 2 ± 3) and decreased the moment of resistance (318 mm 3 ± 10) versus non-exposed (371 mm 3 ± 20) at the diaphyseal 18% measure point. At the metaphyseal measure point, the trabecular bone mineral density (121 mg/cm 3 ± 5) was increased versus non-exposed (111 mg/cm 3 ± 3). PCB 126 exposure did not produce any observable changes in bone tissue. The biomechanical testing of the bones did not show any significant changes in bone strength after PCB 153 or PCB 126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126, resulted in altered bone composition in female goat offspring

  2. Prenatal exposure to dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring.

    Directory of Open Access Journals (Sweden)

    Lee O'Sullivan

    Full Text Available Exposure to synthetic glucocorticoids during development can result in later cardiovascular and renal disease in sheep and rats. Although prenatal glucocorticoid exposure is associated with impaired renal development, less is known about effects on the developing heart. This study aimed to examine the effects of a short-term exposure to dexamethasone (60 hours from embryonic day 12.5 on the developing mouse heart, and cardiovascular function in adult male offspring. Dexamethasone (DEX exposed fetuses were growth restricted compared to saline treated controls (SAL at E14.5, but there was no difference between groups at E17.5. Heart weights of the DEX fetuses also tended to be smaller at E14.5, but not different at E17.5. Cardiac AT1aR, Bax, and IGF-1 mRNA expression was significantly increased by DEX compared to SAL at E17.5. In 12-month-old offspring DEX exposure caused an increase in basal blood pressure of ~3 mmHg. In addition, DEX exposed mice had a widened pulse pressure compared to SAL. DEX exposed males at 12 months had an approximate 25% reduction in nephron number compared to SAL, but no difference in cardiomyocyte number. Exposure to DEX in utero appears to adversely impact on nephrogenesis and heart growth but is not associated with a cardiomyocyte deficit in male mice in adulthood, possibly due to compensatory growth of the myocardium following the initial insult. However, the widened pulse pressure may be indicative of altered vascular compliance.

  3. Rim Structure, Stratigraphy, and Aqueous Alteration Exposures Along Opportunity Rover's Traverse of the Noachian Endeavour Crater

    Science.gov (United States)

    Crumpler, L.S.; Arvidson, R. E.; Golombek, M.; Grant, J. A.; Jolliff, B. L.; Mittlefehldt, D. W.

    2017-01-01

    The Mars Exploration Rover Opportunity has traversed 10.2 kilometers along segments of the west rim of the 22-kilometer-diameter Noachian Endeavour impact crater as of sol 4608 (01/09/17). The stratigraphy, attitude of units, lithology, and degradation state of bedrock outcrops exposed on the crater rim have been examined in situ and placed in geologic context. Structures within the rim and differences in physical properties of the identified lithologies have played important roles in localizing outcrops bearing evidence of aqueous alteration.

  4. Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study

    Directory of Open Access Journals (Sweden)

    Chivukula VK

    2015-01-01

    Full Text Available Venkat Keshav Chivukula,1 Benjamin L Krog,1,2 Jones T Nauseef,2 Michael D Henry,2 Sarah C Vigmostad1 1Department of Biomedical Engineering, 2Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, USA Abstract: Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH and transformed prostate cancer cells (PC-3 were used in this study. The Young's modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared and immediately after exposure to high (6,400 dyn/cm2 and low (510 dyn/cm2 FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young's modulus after exposure to high FSS and a ~47% increase in Young's modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young's modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young's modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study

  5. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

    Science.gov (United States)

    von Poser Toigo, E; Huffell, A P; Mota, C S; Bertolini, D; Pettenuzzo, L F; Dalmaz, C

    2015-04-01

    The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    Science.gov (United States)

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. Published by Elsevier Ltd.

  8. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

    1983-01-01

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  9. Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development.

    Science.gov (United States)

    Macaulay, Laura J; Chernick, Melissa; Chen, Albert; Hinton, David E; Bailey, Jordan M; Kullman, Seth W; Levin, Edward D; Stapleton, Heather M

    2017-01-01

    Polybrominated diphenyl ethers (PBDEs) and their metabolites (e.g., hydroxylated BDEs [OH-BDEs]) are contaminants frequently detected together in human tissues and are structurally similar to thyroid hormones. Thyroid hormones partially mediate metamorphic transitions between life stages in zebrafish, making this a critical developmental window that may be vulnerable to chemicals disrupting thyroid signaling. In the present study, zebrafish were exposed to 6-OH-BDE-47 (30 nM; 15 μg/L) alone, or to a low-dose (30 μg/L) or high-dose (600 μg/L) mixture of PentaBDEs, 6-OH-BDE-47 (0.5-6 μg/L), and 2,4,6-tribromophenol (5-100 μg/L) during juvenile development (9-23 d postfertilization) and evaluated for developmental endpoints mediated by thyroid hormone signaling. Fish were sampled at 3 time points and examined for developmental and skeletal morphology, apical thyroid and skeletal gene markers, and modifications in swimming behavior (as adults). Exposure to the high-dose mixture resulted in >85% mortality within 1 wk of exposure, despite being below reported acute toxicity thresholds for individual congeners. The low-dose mixture and 6-OH-BDE-47 groups exhibited reductions in body length and delayed maturation, specifically relating to swim bladder, fin, and pigmentation development. Reduced skeletal ossification was also observed in 6-OH-BDE-47-treated fish. Assessment of thyroid and osteochondral gene regulatory networks demonstrated significantly increased expression of genes that regulate skeletal development and thyroid hormones. Overall, these results indicate that exposures to PBDE/OH-BDE mixtures adversely impact zebrafish maturation during metamorphosis. Environ Toxicol Chem 2017;36:36-48. © 2016 SETAC. © 2016 SETAC.

  10. Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta)

    Science.gov (United States)

    Jandegian, Caitlin M.; Deem, Sharon L.; Bhandari, Ramji K.; Holliday, Casey M.; Nicks, Diane; Rosenfeld, Cheryl S.; Selcer, Kyle; Tillitt, Donald E.; vom Saal, Fredrick S.; Velez, Vanessa; Yang, Ying; Holliday, Dawn K.

    2015-01-01

    Environmental chemicals can disrupt endocrine signaling and adversely impact sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical commonly found in a variety of habitats. In this study, we used painted turtles (Chrysemys picta), which have temperature-dependent sex determination (TSD), as an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that BPA would override TSD and disrupt sexual development. We incubated farm-raised turtle eggs at the male-producing temperature (26 °C), randomly assigned individuals to treatment groups: control, vehicle control, 17β-estradiol (E2, 20 ng/g-egg) or 0.01, 1.0, 100 μg BPA/g-egg and harvested tissues at hatch. Typical female gonads were present in 89% of the E2-treated “males”, but in none of the control males (n = 35). Gonads of BPA-exposed turtles had varying amounts of ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the medulla. Although the percentage of males with OLCs increased with BPA dose (BPA-low = 30%, BPA-medium = 33%, BPA-high = 39%), this difference was not significant (p = 0.85). In all three BPA treatments, SOX9 patterns revealed disorganized medullary testicular tubules and β-catenin expression in a thickened cortex. Liver vitellogenin, a female-specific liver protein commonly used as an exposure biomarker, was not induced by any of the treatments. Notably, these results suggest that developmental exposure to BPA disrupts sexual differentiation in painted turtles. Further examination is necessary to determine the underlying mechanisms of sex reversal in reptiles and how these translate to EDC exposure in wild populations.

  11. Postnatal development of rat pups is altered by prenatal methamphetamine exposure.

    Science.gov (United States)

    Slamberová, Romana; Pometlová, Marie; Charousová, Petra

    2006-01-01

    There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MA-exposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks

  12. Regulation of ex vivo tyrosine hydroxylase (TH) activity is not altered by chronic lead (Pb) exposure

    International Nuclear Information System (INIS)

    Lasley, S.M.; Green, M.C.

    1991-01-01

    Previous studies have suggested that chronic Pb exposure results in impaired regulation of CNS dopamine (DA) synthesis in rats. The present study was designed to directly assess TH activity in exposed animals compared to controls, employing a pharmacological model that assesses the functional status of dopaminergic synthesis-modulating autoreceptors. At birth dams received 0.2% Pb acetate in drinking water. Offspring were weaned to and maintained on the same solution until termination at 60 or 120 days. Rats were given saline or a DA agonist (EMD 23448 or CGS 15855A) 45 min before sacrifice followed 15 min later by gamma-butyrolactone (GBL). Regional TH activity was measured by a modification of the tritium release method. DA content was determined by liquid chromatography. The ability of EMD 23448 to prevent the GBL-induced increase in DA content was significantly diminished in caudate-putamen (C-P) of exposed rats compared to controls, similar to previous observations. However, an analogous effect of Pb on TH activity in this drug model was not observed using CGS 15855A in rats either 60 or 120 days of age. These findings suggest that chronic Pb exposure has no effect on autoreceptor-mediated regulation of TH in DA neurons when TH activity is measured ex vivo

  13. Prenatal ethanol exposure alters steroidogenic enzyme activity in newborn rat testes.

    Science.gov (United States)

    Kelce, W R; Rudeen, P K; Ganjam, V K

    1989-10-01

    We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.

  14. Prenatal and lactational exposure to low-doses of bisphenol A alters adult mice behavior.

    Science.gov (United States)

    Nakamura, Keiko; Itoh, Kyoko; Dai, Hongmei; Han, Longzhe; Wang, Xiaohang; Kato, Shingo; Sugimoto, Tohru; Fushiki, Shinji

    2012-01-01

    Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in dentistry and various industries. We previously reported that BPA affected murine neocortical development by accelerating neuronal differentiation/migration, resulting in abnormal neocortical architecture as well as aberrant thalamocortical connections in the brains of adult mice. The aim of this study was to investigate whether prenatal and lactational BPA exposure affected behavior in adult mice. Pregnant mice were injected subcutaneously with 20μg/kg of BPA daily from embryonic day 0 (E0) until postnatal day 21 (P21). Control animals received a vehicle alone. Behavioral tests (n=15-20) were conducted at postnatal 3weeks (P3W) and P10-15W. After an open-field test, an elevated plus maze and Morris water maze tests were performed. The total distance in the elevated plus maze test at P3W and in the open-field test at P10W was significantly decreased in the BPA-exposed group, compared with the control group. Significant sex differences were observed in the time spent in the central area in the open-field test at P3W and in the total distance in the elevated plus maze test at P11W. These results indicated that prenatal and lactational BPA exposure disturbed the murine behavior in the postnatal development period and the adult mice. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Exposure and Figure Out of Climate Induced Alterations in the Wetlands of Banglades

    Science.gov (United States)

    Siddiquee, S. A.; Rahman, M. Z.

    2015-12-01

    Unique geographic location and geo-morphological conditions of Bangladesh have made the wetlands of this country one of the most vulnerable to climate change. Wetland plays a crucial role in maintaining the ecological balance of ecosystems and cultural figures and which occupy around 50% of the area. Drought, excessive temperature, mountain snowfields and glaciers melting, riverbank erosion, salinity intrusion, flashflood, storm surges, higher water temperatures, precipitation anomalies, coastal cyclones, seasonal anomalies and extremes are main threats to the wetland ecosystem. Enhanced UV-B radiation and increased summer precipitation will significantly increase dissolved organic carbon concentrations altering major biogeochemical cycles and also will result into the expansion of range for many invasive aquatic weeds. Generally, rising temperature will lower water quality through a fall in oxygen concentrations, release of phosphorus from sediments, increased thermal stability, and altered mixing patterns. As a result biodiversity is getting degraded, many species of flora and fauna are getting threatened, and wetland-based ecosystem is getting degenerated. At the same time, the living conditions of local people are deteriorating as livelihoods, socioeconomic institutions, and extensive cultural values as well. For conserving and managing wetlands technology, legislation, educational knowledge, action plan strategy and restoration practices are required. In order to address the human needs in the changing climate community-based adaptation approaches and wetland restoration, practices had been taken in almost every type of wetlands in Bangladesh. Therefore, Bangladesh now needs a comprehensive strategy and integrated system combining political, economic, social, technological approaches and institutional supports to address sustainable wetland restoration, conservation and the newly added crisis, climate change.

  16. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

    Science.gov (United States)

    Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

    2016-08-01

    Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

  17. Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells

    International Nuclear Information System (INIS)

    Jantzen, Kim; Møller, Peter; Karottki, Dorina Gabriela; Olsen, Yulia; Bekö, Gabriel; Clausen, Geo; Hersoug, Lars-Georg; Loft, Steffen

    2016-01-01

    Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related to leukocyte-mediated oxidative stress. The study utilized a cross sectional design performed in 58 study participants from a larger cohort. Levels of circulating endothelial progenitor cells, defined as either late (CD34 + KDR + cells) or early (CD34 + CD133 + KDR + cells) subsets were measured using polychromatic flow cytometry. We additionally measured production of reactive oxygen species in leukocyte subsets (lymphocytes, monocytes and granulocytes) by flow cytometry using intracellular 2′,7′-dichlorofluoroscein. The measurements encompassed both basal levels of reactive oxygen species production and capacity for reactive oxygen species production for each leukocyte subset. We found that the late endothelial progenitor subset was negatively associated with levels of ultrafine particles measured within the participant residences and with reactive oxygen species production capacity in lymphocytes. Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate that exposure to fine and ultrafine particles derived from indoor sources may have adverse effects on human vascular health.

  18. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    International Nuclear Information System (INIS)

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E.

    2007-01-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time

  19. Altered miRNA expression in the cervix during pregnancy associated with lead and mercury exposure

    Science.gov (United States)

    Sanders, Alison P; Burris, Heather H; Just, Allan C; Motta, Valeria; Amarasiriwardena, Chitra; Svensson, Katherine; Oken, Emily; Solano-Gonzalez, Maritsa; Mercado-Garcia, Adriana; Pantic, Ivan; Schwartz, Joel; Tellez-Rojo, Martha M; Baccarelli, Andrea A; Wright, Robert O

    2015-01-01

    Aim: Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. Materials & methods: We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Results: Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. Conclusion: The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy. PMID:26418635

  20. Alterations in biochemical markers due to mercury (Hg) exposure and its influence on infant's neurodevelopment.

    Science.gov (United States)

    Al-Saleh, Iman; Elkhatib, Rola; Al-Rouqi, Reem; Abduljabbar, Mai; Eltabache, Chafica; Al-Rajudi, Tahreer; Nester, Michael

    2016-11-01

    This study examined the role of oxidative stress due to mercury (Hg) exposure on infant's neurodevelopmental performance. A total of 944 healthy Saudi mothers and their respective infants (aged 3-12 months) were recruited from 57 Primary Health Care Centers in Riyadh City. Total mercury (Hg) was measured in mothers and infants urine and hair samples, as well as mother's blood and breast milk. Methylmercury (MeHg) was determined in the mothers and infants' hair and mother's blood. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and porphyrins were used to assess oxidative stress. The infant's neurodevelopment was evaluated using Denver Developmental Screening Test II (DDST-II) and Parents' Evaluation of Developmental Status. The median total Hg levels in mother's urine, infant's urine, mother's hair, infant's hair, and mother's blood and breast milk were 0.995μg/l, 0.716μg/l, 0.118μg/g dw, 0.101μg/g dw, 0.635μg/l, and 0.884μg/l respectively. The median MeHg levels in mother's hair, infant's hair, and mother's blood were 0.132μg/g dw, 0.091μg/g dw, and 2.341μg/l respectively. A significant interrelationship between mothers and infants Hg measures in various matrices was noted. This suggests that mother's exposure to different forms of Hg (total and/or MeHg) from various sources contributed significantly to the metal body burden of their respective infants. Even though Hg exposure was low, it induced high oxidative stress in mothers and infants. The influence of multiplicative interaction terms between Hg measures and oxidative stress biomarkers was tested using multiple regression analysis. Significant interactions between the urinary Hg levels in mothers and infants and oxidative stress biomarkers (8-OHdG and MDA) were noted. The MeHg levels in mother-infant hair revealed similar interaction patterns. The p-values for both were below 0.001. These observations suggest that the exposure of our infants to Hg via mothers either during

  1. Altered Microbiota Contributes to Reduced Diet-Induced Obesity upon Cold Exposure

    DEFF Research Database (Denmark)

    Ziętak, Marika; Kovatcheva-Datchary, Petia; Markiewicz, Lidia H

    2016-01-01

    Maintenance of body temperature in cold-exposed animals requires induction of thermogenesis and management of fuel. Here, we demonstrated that reducing ambient temperature attenuated diet-induced obesity (DIO), which was associated with increased iBAT thermogenesis and a plasma bile acid profile...... similar to that of germ-free mice. We observed a marked shift in the microbiome composition at the phylum and family levels within 1 day of acute cold exposure and after 4 weeks at 12°C. Gut microbiota was characterized by increased levels of Adlercreutzia, Mogibacteriaceae, Ruminococcaceae......, and Desulfovibrio and reduced levels of Bacilli, Erysipelotrichaceae, and the genus rc4-4. These genera have been associated with leanness and obesity, respectively. Germ-free mice fed a high-fat diet at room temperature gained less adiposity and improved glucose tolerance when transplanted with caecal microbiota...

  2. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

    Directory of Open Access Journals (Sweden)

    Yichang Chen

    2016-07-01

    Full Text Available Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures.

  3. High psychosis liability is associated with altered autonomic balance during exposure to Virtual Reality social stressors.

    Science.gov (United States)

    Counotte, Jacqueline; Pot-Kolder, Roos; van Roon, Arie M; Hoskam, Olivier; van der Gaag, Mark; Veling, Wim

    2017-06-01

    Social stressors are associated with an increased risk of psychosis. Stress sensitisation is thought to be an underlying mechanism and may be reflected in an altered autonomic stress response. Using an experimental Virtual Reality design, the autonomic stress response to social stressors was examined in participants with different liability to psychosis. Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra-high risk for psychosis, 42 siblings of patients with psychosis and 53 controls were exposed to social stressors (crowdedness, ethnic minority status and hostility) in a Virtual Reality environment. Heart rate variability parameters and skin conductance levels were measured at baseline and during Virtual Reality experiments. High psychosis liability groups had significantly increased heart rate and decreased heart rate variability compared to low liability groups both at baseline and during Virtual Reality experiments. Both low frequency (LF) and high frequency (HF) power were reduced, while the LF/HF ratio was similar between groups. The number of virtual social stressors significantly affected heart rate, HF, LF/HF and skin conductance level. There was no interaction between psychosis liability and amount of virtual social stress. High liability to psychosis is associated with decreased parasympathetic activity in virtual social environments, which reflects generally high levels of arousal, rather than increased autonomic reactivity to social stressors. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny.

    Science.gov (United States)

    Bacchi, André D; Ponte, Bianca; Vieira, Milene L; de Paula, Jaqueline C C; Mesquita, Suzana F P; Gerardin, Daniela C C; Moreira, Estefânia G

    2013-01-01

    Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams' bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.

  5. Mainstream cigarette smoke exposure alters cytochrome P4502G1 expression in F344 rat olfactory mucosa

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Nikula, K.J.; Lewis, J.L.; Finch, G.L.; Belinsky, S.A.; Dahl, A.R.

    1994-01-01

    Inhalation of mainstream cigarette smoke (MCS) by rats results in multifocal rhinitis, mucous hypersecretion, nasal epithelial hyperplasia and metaplasia, and focal olfactory mucosal atrophy. In humans, cigarette smoking causes long-term, dose-related alterations in olfactory function in both current and former smokers. An olfactory-specific cytochrome P450 has been identified in rabbits and rats. The presence of olfactory-specific P450s, as well as relatively high levels of other biotransformation enzymes, such as NADPH-cytochrome P450 reductase and UDP-glucuronosyl transferase, in the olfactory neuroepithelium suggest that these enzyme systems may play a role in olfaction. This hypothesis is strengthened by the observation that, in rats, the temporal gene activation of P4502G1 coincides with the postnatal increase in the sensitivity of olfactory response to odorants. The purpose of this investigation was to examine the effect of MCS exposure on P4502G1 protein expression

  6. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    International Nuclear Information System (INIS)

    Liu, Qing; Rise, Matthew L.; Spitsbergen, Jan M.; Hori, Tiago S.; Mieritz, Mark; Geis, Steven; McGraw, Joseph E.; Goetz, Giles; Larson, Jeremy; Hutz, Reinhold J.; Carvan, Michael J.

    2013-01-01

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  7. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States); Rise, Matthew L. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Spitsbergen, Jan M. [Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331 (United States); Hori, Tiago S. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Mieritz, Mark; Geis, Steven [Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706 (United States); McGraw, Joseph E. [School of Pharmacy, Concordia University Wisconsin, 12800 North Lake Shore Drive, Mequon, WI 53097 (United States); Goetz, Giles [School of Aquatic and Fishery Sciences, University of Washington, 1122 Northeast Boat Street, Seattle, WA 98195 (United States); Larson, Jeremy; Hutz, Reinhold J. [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); Carvan, Michael J., E-mail: carvanmj@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-09-15

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  8. Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

    Science.gov (United States)

    Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

    2018-03-01

    Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

  9. Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood.

    Science.gov (United States)

    Varlinskaya, Elena I; Kim, Esther U; Spear, Linda P

    2017-01-01

    We previously observed lasting and sex-specific detrimental consequences of early adolescent intermittent ethanol exposure (AIE), with male, but not female, rats showing social anxiety-like alterations when tested as adults. The present study used Sprague Dawley rats to assess whether social alterations induced by AIE (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45) are further exacerbated by stressors later in life. Another aim was to determine whether AIE alone or in combination with stress influenced intake of a sweetened ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone (Experiment 2) under social circumstances. Animals were exposed to restraint on P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged after AIE in non-stressed males, but not females, whereas stress-induced social anxiety was evident only in water-exposed males and females. Adult-typical habituation of the CORT response to repeated restraint was not evident in adult animals after AIE, a lack of habituation reminiscent of that normally evident in adolescents. Neither AIE nor stress affected ethanol intake under social circumstances, although AIE and restraint independently increased adolescent-typical play fighting in males during social drinking. Among males, the combination of AIE and restraint suppressed "supersac" intake; this index of depression-like behavior was not seen in females. The results provide experimental evidence associating adolescent alcohol exposure, later stress, anxiety, and depression, with young adolescent males being particularly vulnerable to long-lasting adverse effects of repeated ethanol. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

    Science.gov (United States)

    Supriya, Ch.; Reddy, P. Sreenivasula

    2015-06-01

    Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility

  11. Physical habitat and its alteration: A common ground for exposure of amphibians to environmental stressors

    Science.gov (United States)

    Bishop, Christine A.; Cunnington, David C.; Fellers, Gary M.; Gibbs, James P.; Pauli, Bruce D.; Rothermel, Betsie B.; Linder, Greg L.; Krest, Sherry K.; Sparling, Donald W.

    2003-01-01

    Amphibians as a class of vertebrates have persisted for hundreds of millions of years (Stebbins and Cohen 1995), but they are currently threatened by a variety of stressors, many resulting from human-related alterations of the environment. Most species of amphibians live closely associated with moist environments throughout their life and have evolved specialized adaptations that conserve water and reduce desiccation (Stebbins and Cohen 1995; Henry 2000; Chapter 2A). Amphibians are ectotherms, so their body temperatures fluctuate with the local environment. Latitude, elevation, and habitat affect environmental temperature and have a strong influence on amphibian distributions. Despite these physiological and habitat constraints, the 4750 species of amphibians in the world today have exploited a wide variety of habitats that range from dry deserts to tropical rain forests and from sea level to elevations above 4000 m (McDairmid and Mitchell 2000).The direct loss of suitable habitat has had a profound effect on amphibian populations (Johnson 1992), as it has on nearly all species of wildlife. In the U.S., 53% of wetlands have been lost to human development in the last 200 years (Dahl 1990). Similar loss of wetlands has occurred throughout much of the world, especially in developing countries (Miller 1993). In many regions, deforestation has reduced or eliminated suitable terrestrial habitats, and this may prove to be the largest global threat to amphibian populations (Johnson 1992). Eight thousand years ago, forests covered approximately 40% of the world’s land (6 billion hectares), but by 1997, the world’s forests had been reduced to 3.5 billion hectares, a 42% loss worldwide (CIDA 2001). The effect of habitat loss is generally both obvious and predictable; with increasing restriction of suitable habitat, amphibian populations will probably not survive. The anthropogenic effects on the quality of the habitat that remains are often less obvious.

  12. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    Science.gov (United States)

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  13. Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

    Science.gov (United States)

    Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

    2017-01-01

    Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD) cycle and in complete darkness (DD). At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN) using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances. PMID:28970786

  14. Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

    Science.gov (United States)

    Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

    2017-01-01

    DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

  15. Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Sônia de Fátima Soto

    Full Text Available Female Wistar rats were exposed to filtered air (F or to concentrated fine particulate matter (P for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFβ1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR.Exposure to P decreased the placental mass, size, and surface area as well as the TGFβ1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII and its receptors AT1 (AT1R and AT2 (AT2R were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group.Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

  16. Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players.

    Science.gov (United States)

    Stamm, Julie M; Koerte, Inga K; Muehlmann, Marc; Pasternak, Ofer; Bourlas, Alexandra P; Baugh, Christine M; Giwerc, Michelle Y; Zhu, Anni; Coleman, Michael J; Bouix, Sylvain; Fritts, Nathan G; Martin, Brett M; Chaisson, Christine; McClean, Michael D; Lin, Alexander P; Cantu, Robert C; Tripodis, Yorghos; Stern, Robert A; Shenton, Martha E

    2015-11-15

    Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure.

  17. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

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    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  18. Experimental exposure of African catfish Clarias Gariepinus (Burchell, 1822 to phenol: Clinical evaluation, tissue alterations and residue assessment

    Directory of Open Access Journals (Sweden)

    Mai D. Ibrahem

    2012-04-01

    Full Text Available There is lack of information regarding; the toxicological and pathological consequences of phenol stressed Clarias gariepinus; as well as; the susceptibility of the stressed fish to disease occurrence. Static renewal bioassay was experimentally conducted to evaluate the toxic effects of phenol on the African catfish C. gariepinus. Ninety-six-hour acute toxicity tests revealed that the median lethal concentration of phenol (LC50 is 35 mg/L by immersion. Four experimental fish groups were assigned for 3 weeks exposure test; three were exposed 20%, 50% and 70% LC50, the fourth control fish group received a vehicle of dechlorinated water. Abnormal signs including cessation of feeding, nervous manifestations; skin expressed perfuses mucous, black patches with skin erosion and ulcerations in the later stages. All observations were correlated to the time and dose of exposure. Post mortem examination revealed adhesion of the internal organs. For tissue alterations; Skin, gills, brain, liver and kidney showed variable degrees of degenerative changes and necrosis. Muscle residues shown in mean ± SE were 4.3 ± 0.05 and 6.65 ± 0.05 ppm in groups that received 20 and 50% LD50, respectively. Infection with Aeromonas hydrophila resulted in high percent of mortalities with a non significant difference between the challenged fish groups. The study cleared that phenol is toxic to C. gariepinus under experimental conditions.

  19. Impaired sustained attention and altered reactivity to errors in an animal model of prenatal cocaine exposure.

    Science.gov (United States)

    Gendle, Mathew H; Strawderman, Myla S; Mactutus, Charles F; Booze, Rosemarie M; Levitsky, David A; Strupp, Barbara J

    2003-12-30

    Although correlations have been reported between maternal cocaine use and impaired attention in exposed children, interpretation of these findings is complicated by the many risk factors that differentiate cocaine-exposed children from SES-matched controls. For this reason, the present dose-response study (0, 0.5, 1.0, or 3.0 mg/kg cocaine HCl) was designed to explore the effect of prenatal cocaine exposure on visual attention in a rodent model, using an intravenous injection protocol that closely mimics the pharmacokinetic profile and physiological effects of human recreational cocaine use. In adulthood, animals were tested on an attention task in which the duration, location, and onset time of a brief visual cue varied randomly between trials. The 3.0 mg/kg exposed males committed significantly more omission errors than control males during the final 1/3 of each testing session, specifically on trials that followed an error, which implicates impaired sustained attention and increased reactivity to committing an error. During the final 1/3 of each testing session, the 0.5 and 1.0 mg/kg exposed females took longer to enter the testing alcove at trial onset, and failed to enter the alcove more frequently than control females. Because these effects were not seen in other tasks of similar duration and reinforcement density, these findings suggest an impairment of sustained attention. This inference is supported by the finding that the increase in omission errors in the final block of trials in each daily session (relative to earlier in the session) was significantly greater for the 1.0 mg/kg females than for controls, a trend also seen for the 0.5 mg/kg group. Unlike the cocaine-exposed males, who remain engaged in the task when attention is waning, the cocaine-exposed females appear to opt for another strategy; namely, refusing to participate when their ability to sustain attention is surpassed.

  20. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  2. Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

  3. Exposure to monomethylarsonous acid (MMAIII) leads to altered selenoprotein synthesis in a primary human lung cell model

    International Nuclear Information System (INIS)

    Meno, Sarah R.; Nelson, Rebecca; Hintze, Korry J.; Self, William T.

    2009-01-01

    Monomethylarsonous acid (MMA III ), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMA III is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMA III on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMA III resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMA III treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMA III , as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMA III induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMA III alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.

  4. Selenium exposure results in reduced reproduction in an invasive ant species and altered competitive behavior for a native ant species

    International Nuclear Information System (INIS)

    De La Riva, Deborah G.; Trumble, John T.

    2016-01-01

    Competitive ability and numerical dominance are important factors contributing to the ability of invasive ant species to establish and expand their ranges in new habitats. However, few studies have investigated the impact of environmental contamination on competitive behavior in ants as a potential factor influencing dynamics between invasive and native ant species. Here we investigated the widespread contaminant selenium to investigate its potential influence on invasion by the exotic Argentine ant, Linepithema humile, through effects on reproduction and competitive behavior. For the fecundity experiment, treatments were provided to Argentine ant colonies via to sugar water solutions containing one of three concentrations of selenium (0, 5 and 10 μg Se mL −1 ) that fall within the range found in soil and plants growing in contaminated areas. Competition experiments included both the Argentine ant and the native Dorymyrmex bicolor to determine the impact of selenium exposure (0 or 15 μg Se mL −1 ) on exploitation- and interference-competition between ant species. The results of the fecundity experiment revealed that selenium negatively impacted queen survival and brood production of Argentine ants. Viability of the developing brood was also affected in that offspring reached adulthood only in colonies that were not given selenium, whereas those in treated colonies died in their larval stages. Selenium exposure did not alter direct competitive behaviors for either species, but selenium exposure contributed to an increased bait discovery time for D. bicolor. Our results suggest that environmental toxins may not only pose problems for native ant species, but may also serve as a potential obstacle for establishment among exotic species. - Highlights: • Argentine ant colonies exposed to selenium had reduced fecundity compared to unexposed colonies. • Viability of offspring was negatively impacted by selenium. • Queen survival was reduced in colonies

  5. Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates.

    Science.gov (United States)

    Rabovsky, J; Judy, D J; Rodak, D J; Petersen, M

    1986-06-01

    We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists

  6. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

    Directory of Open Access Journals (Sweden)

    Perinaaz R Wadia

    Full Text Available Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a associated with changes in mRNA expression reflecting estrogenic actions and/or b dependent on the estrogen receptor α (ERα, we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2 on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.

  7. Environmentally relevant concentrations of di(2-ethylhexyl)phthalate exposure alter larval growth and locomotion in medaka fish via multiple pathways.

    Science.gov (United States)

    Yang, Wen-Kai; Chiang, Li-Fen; Tan, Shi-Wei; Chen, Pei-Jen

    2018-06-01

    Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer, with evidence of ubiquitous human exposure and widespread occurrence in the aquatic environment. It is an emerging environmental pollutant with regulatory priority; however, most studies have focused on the toxicity of DEHP related to endocrine disruption and reproduction in mammals. The ecotoxicological impact of phthalates (e.g., DEHP) on early life stages of fish under environmentally relevant concentrations of chronic exposure remains unclear. In this study, 7-day post-hatching fry of medaka fish (Oryzias latipes) underwent 21-day continuous exposure to DEHP solutions at 20, 100 and 200 μg/L to assess the effects on fish development and locomotion and related toxic mechanisms. Larval mortality was low with DEHP (20-200 μg/L) within 21 days, but such exposure significantly reduced fish body weight and length and altered swimming behavior. At 21 days, DEHP exposure resulted in specific patterns of larval locomotion (e.g., increased maximum velocity and absolute turn angle) and dose-dependently increased the mRNA expression of acetylcholinesterase (ache) but did not alter AChE activity. Transcriptional expression of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase and peroxisome proliferation-activated receptor and retinoid X receptor genes was significantly suppressed with 21-day DEHP exposure (20-200 μg/L), with marginal alteration in reactive oxygen species levels and antioxidant activities within the dosing period. As well, DEHP altered the mRNA expression of p53-regulated apoptosis pathways, such as upregulated p53, p21 and bcl-2 and downregulated caspase-3 expression, with increased enzymatic activity of caspase-3 in larvae. Our results suggest that toxic mechanisms of waterborne DEHP altered fish growth and locomotion likely via a combined effect of oxidative stress, neurotoxicity and apoptosis pathways. Copyright © 2018

  8. Vinpocetine and Vitamin E Modulates Some Biochemical Alterations Induced by Exposure to Ionizing Radiation and Chloropyrifos in Rats

    International Nuclear Information System (INIS)

    Kamal El-Dein, E.M.; Abd El-Azime, A.SH.

    2013-01-01

    Acapi-Cav is a well balanced and well tolerated formula containing vinpocetine and vitamin E. The objective of this study was to investigate the effect of vinpocetine and vitamin E on the oxidative stress, electrolytes and monoamines level in rats exposed to ionizing radiation (gamma rays), chloropyrifos (CPF) as well as rats exposed to a combination of gamma rays and CPF. Irradiation was performed by whole body exposure of rats to 8 Gy delivered at 1 Gy every 4 days. CPF was administered to rats by oral gavages at a dose of 3.6 mg/kg body weight ( 1/10 LD50 ) daily for 30 days. Vinpocetine and vitamin E were administered to rats by oral gavages at a dose of 20 mg/kg body weight daily during 7 days before starting the experiment and continued during the period of exposure to gamma rays and/or CPF. The results revealed significant increase of malondialdehyde (MDA) level associated with a significant decrease of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the blood of rats exposed to gamma rays and/or CPF indicating oxidative stress. The levels of serum electrolytes (sodium Na + , potassium K + , calcium Ca ++ and magnesium Mg) showed significant decrease. Serum dopamine (DA) level was decreased and norepinephrine (NE) was increased while epinephrine (EPI) showed non-significant change. The level of serum monoamine oxidase (MAO) showed significant increase. The administration of vinpocetine and vitamin E to rats exposed to gamma rays and/or CPF significantly reduced the amount of MDA which associated with an increase in the level of antioxidants and significant improvement was recorded for electrolytes level. The results demonstrated that vinpocetine and vitamin E significantly attenuated the increase of MAO and induced significant amelioration in the level of monoamines. It could be concluded that vinpocetine and vitamin E might protect the body from oxidative damage and electrolytes and monoamines alterations in rats exposed to gamma rays

  9. Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure.

    Science.gov (United States)

    Ogi, Hiroshi; Itoh, Kyoko; Ikegaya, Hiroshi; Fushiki, Shinji

    2015-09-01

    Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes. C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams. The IntelliCage behavioral experiments were conducted from P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions were measured by high performance liquid chromatography. Furthermore, the associations between the neurotransmitter levels and the behavioral indices were statistically analyzed. In females exposed to BPA, the GABA and Glu levels in almost all regions, and the NE levels in the cortex, hypothalamus and thalamus were higher than those in the controls. In males exposed to BPA, the GABA levels in the amygdala and hippocampus showed lower values, while Glu levels were higher in some regions, compared with the controls. In regard to the associations, the number of "diurnal corner visits without drinking" was correlated with the NE levels in the cortex and thalamus in females. The "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus in males. These results suggest that prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA and Glu systems, resulting in behavioral alterations. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. Altered Gene Expressions and Cytogenetic Repair Efficiency in Cells with Suppressed Expression of XPA after Proton Exposure

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Gridley, Daila S.; Mehta, Satish K.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Cellular responses to damages from ionizing radiation (IR) exposure are influenced not only by the genes involved in DNA double strand break (DSB) repair, but also by non- DSB repair genes. We demonstrated previously that suppressed expression of several non-DSB repair genes, such as XPA, elevated IR-induced cytogenetic damages. In the present study, we exposed human fibroblasts that were treated with control or XPA targeting siRNA to 250 MeV protons (0 to 4 Gy), and analyzed chromosome aberrations and expressions of genes involved in DNA repair. As expected, after proton irradiation, cells with suppressed expression of XPA showed a significantly elevated frequency of chromosome aberrations compared with control siRNA treated (CS) cells. Protons caused more severe DNA damages in XPA knock-down cells, as 36% cells contained multiple aberrations compared to 25% in CS cells after 4Gy proton irradiation. Comparison of gene expressions using the real-time PCR array technique revealed that expressions of p53 and its regulated genes in irradiated XPA suppressed cells were altered similarly as in CS cells, suggesting that the impairment of IR induced DNA repair in XPA suppressed cells is p53-independent. Except for XPA, which was more than 2 fold down regulated in XPA suppressed cells, several other DNA damage sensing and repair genes (GTSE1, RBBP8, RAD51, UNG and XRCC2) were shown a more than 1.5 fold difference between XPA knock-down cells and CS cells after proton exposure. The possible involvement of these genes in the impairment of DNA repair in XPA suppressed cells will be further investigated.

  11. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    Energy Technology Data Exchange (ETDEWEB)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India)

    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.

  12. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    International Nuclear Information System (INIS)

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

    2007-01-01

    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 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

  13. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Science.gov (United States)

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  14. Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease.

    Science.gov (United States)

    Huang, Yuqi; Zhao, Zhe; Wei, Xiaoli; Zheng, Yong; Yu, Jianqiang; Zheng, Jianquan; Wang, Liyun

    2016-07-01

    Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP-treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to

  15. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Passier, Robert [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); MIRA, University of Twente (Netherlands); Tertoolen, Leon G.J.; Mummery, Christine L. [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Casini, Simona, E-mail: s.casini@amc.uva.nl [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-27

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.

  16. Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

    Science.gov (United States)

    Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

    2007-09-01

    Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

  17. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

    International Nuclear Information System (INIS)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien; Passier, Robert; Tertoolen, Leon G.J.; Mummery, Christine L.; Casini, Simona

    2015-01-01

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca"2"+ transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I_C_a_,_L and action potential characteristics in hESC-CMs.

  18. Aqueous exposure to the progestin, levonorgestrel, alters anal fin development and reproductive behavior in the eastern mosquitofish (Gambusia holbrooki)

    Science.gov (United States)

    Frankel, Tyler E.; Meyer, Michael T.; Orlando, Edward F.

    2016-01-01

    differences were not significant between the two treatments. LNG caused significant increases in the 4:6 anal fin ratio of males exposed to 100 ng/L, with no effects observed in the 10 ng/L treatment. In addition, the reproductive behavior of control males paired with female mosquitofish exposed to 100 ng/L LNG was also altered, for these males spent more time exhibiting no reproductive behavior, had decreased attending behavior, and a lower number of gonopodial thrusts compared to control males paired to control female mosquitofish. Given the rapid effects on both anal fin morphology and behavior observed in this study, the mosquitofish is an excellent sentinel species for the detection of exposure to LNG and likely other 19-nortestosterone derived contraceptive progestins in the environment.

  19. Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

    Science.gov (United States)

    Malgoyre, Alexandra; Chabert, Clovis; Tonini, Julia; Koulmann, Nathalie; Bigard, Xavier; Sanchez, Hervé

    2017-03-01

    We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism. Therefore, we used a group of pair-fed rats (reproducing the same caloric restriction, as observed in hypoxic animals), in addition to the normoxic control fed ad libitum. The resting respiratory exchange ratio decreased after 21 days of exposure to hypobaric hypoxia (simulated elevation of 5,500 m). The respiration supported by pyruvate and octanoate were unaffected. In contrast, the maximal oxidative respiratory rate for PCoA, the transport of which depends on carnitine palmitoyltransferase 1 (CPT-1), decreased in the rapid-glycolytic EDL and increased in the slow-oxidative SOL, although hypoxia improved affinity for this substrate in both muscle types. PC and PCoA were oxidized similarly in normoxic EDL, whereas chronic hypoxia limited transport at the CPT-1 step in this muscle. The effects of hypoxia were mediated by caloric restriction in the SOL and by hypoxia itself in the EDL. We conclude that improvements in mitochondrial affinity for PCoA, a physiological long-chain fatty acid, would facilitate fatty-acid use at rest after chronic hypoxia independently of quantitative alterations of mitochondria. Conversely, decreasing the maximal oxidation of PCoA in fast-glycolytic muscles would limit fatty-acid use during exercise. NEW & NOTEWORTHY Affinity for low concentrations of long-chain fatty acids (LCFA) in mitochondria skeletal muscles increases after chronic hypoxia. Combined with a lower respiratory exchange ratio, this suggests facility for fatty acid utilization at rest. This fuel preference is related to caloric

  20. Exposure to β-lactams results in the alteration of penicillin-binding proteins in Clostridium perfringens.

    Science.gov (United States)

    Park, Miseon; Rafii, Fatemeh

    2017-06-01

    Clostridium perfringens causes a variety of mild to severe infections in humans and other animals. A decrease in the affinity of penicillin-binding protein (PBP) transpeptidases for β-lactams is considered one of the mechanisms of β-lactam resistance in bacteria. Two strains of C. perfringens isolated from bovines and one isolated from a chicken, which had decreased susceptibility to β-lactams, had variations in the amino acid sequences of the central penicillin-binding regions of the PBPs. β-Lactam-resistant mutants of another C. perfringens strain, ATCC 13124, were selected in vitro to determine the effects of exposure to β-lactams on the PBP genes. Cultures of the wild type rapidly developed resistance to penicillin G, cephalothin and ceftriaxone. The susceptibilities of all of the selected mutants to some other β-lactams also decreased. The largest PBP found in C. perfringens, CPF_2395, appeared to be the primary target of all three drugs. Strain resistant to penicillin G had mutation resulting in the substitution of one amino acid within the central penicillin-binding/transpeptidase domain, but the ceftrioxane and cephalothin-resistant strains had mutations resulting in the substitution of two amino acids in this region. The cephalothin-resistant mutant also had additional mutations in the CPF_0340 and CPF_2218 genes in this critical region. No other mutations were observed in the three other PBPs of the in vitro resistant mutants. Resistance development also altered the growth rate and cell morphology of the mutants, so in addition to the PBPs, some other genes, including regulatory genes, may have been affected during the interaction with β-lactam antibiotics. This is the first study showing the effects of β-lactam drugs on the substitution of amino acids in PBPs of C. perfringens and points to the need for studies to detect other unknown alterations affecting the physiology of resistant strains. Published by Elsevier Ltd.

  1. Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles.

    Science.gov (United States)

    Fedan, Jeffrey S; Thompson, Janet A; Meighan, Terence G; Zeidler-Erdely, Patti C; Antonini, James M

    2017-07-01

    Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167-166.7μg/cm 2 ) were applied apically to NHBEs. After 18h transepithelial potential difference (V t ), resistance (R t ), and short circuit current (I sc ) were measured. Particle effects on Na + and Cl¯ channels and the Na + ,K + ,2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167-16.7μg/cm 2 ) increased basal V t . Only 16.7μg/cm 2 GMA-MS increased basal V t significantly. MMA-SS or GMA-MS exposure potentiated I sc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R t were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V t , R t , and I sc at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na + transport and Na + ,K + ,2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na + absorption and decreased airway surface liquid could compromise defenses against infection. Published by Elsevier Inc.

  2. Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles

    Energy Technology Data Exchange (ETDEWEB)

    Fedan, Jeffrey S., E-mail: jsf2@cdc.gov; Thompson, Janet A.; Meighan, Terence G.; Zeidler-Erdely, Patti C.; Antonini, James M.

    2017-07-01

    Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167–166.7 μg/cm{sup 2}) were applied apically to NHBEs. After 18 h transepithelial potential difference (V{sub t}), resistance (R{sub t}), and short circuit current (I{sub sc}) were measured. Particle effects on Na{sup +} and Cl¯ channels and the Na{sup +},K{sup +},2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167–16.7 μg/cm{sup 2}) increased basal V{sub t}. Only 16.7 μg/cm{sup 2} GMA-MS increased basal V{sub t} significantly. MMA-SS or GMA-MS exposure potentiated I{sub sc} responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R{sub t} were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V{sub t}, R{sub t}, and I{sub sc} at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na{sup +} transport and Na{sup +},K{sup +},2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na{sup +} absorption and decreased airway surface liquid could compromise defenses against infection. - Highlights: • Welding fume particle toxicity was investigated in human bronchial

  3. Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue.

    Science.gov (United States)

    Fiorenza, Amanda M; Shnitko, Tatiana A; Sullivan, Kaitlin M; Vemuru, Sudheer R; Gomez-A, Alexander; Esaki, Julie Y; Boettiger, Charlotte A; Da Cunha, Claudio; Robinson, Donita L

    2018-06-01

    Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it. Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach. Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior. While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are

  4. Chronic prenatal ethanol exposure alters hippocampal GABA(A) receptors and impairs spatial learning in the guinea pig.

    Science.gov (United States)

    Iqbal, U; Dringenberg, H C; Brien, J F; Reynolds, J N

    2004-04-02

    Chronic prenatal ethanol exposure (CPEE) can injure the developing brain, and may lead to the fetal alcohol syndrome (FAS). Previous studies have demonstrated that CPEE upregulates gamma-aminobutyric acid type A (GABA(A)) receptor expression in the cerebral cortex, and decreases functional synaptic plasticity in the hippocampus, in the adult guinea pig. This study tested the hypothesis that CPEE increases GABA(A) receptor expression in the hippocampus of guinea pig offspring that exhibit cognitive deficits in a hippocampal-dependent spatial learning task. Timed, pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight per day), isocaloric-sucrose/pair-feeding, or water throughout gestation. GABA(A) receptor subunit protein expression in the hippocampus was measured at two development ages: near-term fetus and young adult. In young adult guinea pig offspring, CPEE increased spontaneous locomotor activity in the open-field and impaired task acquisition in the Morris water maze. CPEE did not change GABA(A) receptor subunit protein expression in the near-term fetal hippocampus, but increased expression of the beta2/3-subunit of the GABA(A) receptor in the hippocampus of young adult offspring. CPEE did not change either [(3)H]flunitrazepam binding or GABA potentiation of [(3)H]flunitrazepam binding, but decreased the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding, to hippocampal GABA(A) receptors in adult offspring. Correlational analysis revealed a relationship between increased spontaneous locomotor activity and growth restriction in the hippocampus induced by CPEE. Similarly, an inverse relationship was found between performance in the water maze and the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding in the hippocampus. These data suggest that alterations in hippocampal GABA(A) receptor expression and pharmacological properties contribute to hippocampal-related behavioral and cognitive deficits

  5. Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

    Science.gov (United States)

    Suwannasual, Usa; Lucero, JoAnn; McDonald, Jacob D; Lund, Amie K

    2018-01-01

    Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100PM/m 3 vehicle emissions mixture: 30µg PM/m 3 gasoline engine + 70µg PM/m 3 diesel engine emissions; median size ~ 60nm; particle mass size distribution median of ~ 1µm (range: diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity.

    Science.gov (United States)

    Colle, Dirleise; Farina, Marcelo; Ceccatelli, Sandra; Raciti, Marilena

    2018-06-01

    Pesticide exposure has been linked to the pathogenesis of neurodevelopmental and neurodegenerative disorders including autism spectrum disorders, attention deficit/hyperactivity, and Parkinson's disease (PD). Developmental exposure to pesticides, even at low concentrations not harmful for the adult brain, can lead to neuronal loss and functional deficits. It has been shown that prenatal or early postnatal exposure to the herbicide paraquat (PQ) and the fungicide maneb (MB), alone or in combination, causes permanent toxicity in the nigrostriatal dopamine system, supporting the idea that early exposure to these pesticides may contribute to the pathophysiology of PD. However, the mechanisms mediating PQ and MB developmental neurotoxicity are not yet understood. Therefore, we investigated the neurotoxic effect of low concentrations of PQ and MB in primary cultures of rat embryonic neural stem cells (NSCs), with particular focus on cell proliferation and oxidative stress. Exposure to PQ alone or in combination with MB (PQ + MB) led to a significant decrease in cell proliferation, while the cell death rate was not affected. Consistently, PQ + MB exposure altered the expression of major genes regulating the cell cycle, namely cyclin D1, cyclin D2, Rb1, and p19. Moreover, PQ and PQ + MB exposures increased the reactive oxygen species (ROS) production that could be neutralized upon N-acetylcysteine (NAC) treatment. Notably, in the presence of NAC, Rb1 expression was normalized and a normal cell proliferation pattern could be restored. These findings suggest that exposure to PQ + MB impairs NSCs proliferation by mechanisms involving alterations in the redox state.

  7. Propensity of red blood cells to undergo P2X7 receptor-mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging.

    Science.gov (United States)

    Sophocleous, Reece A; Mullany, Phillip R F; Winter, Kelly M; Marks, Denese C; Sluyter, Ronald

    2015-08-01

    Phosphatidylserine (PS) exposure facilitates the removal of red blood cells (RBCs) from the circulation, potentially contributing to the loss of stored RBCs after transfusion, as well as senescent RBCs. Activation of the P2X7 receptor by extracellular adenosine 5'-triphosphate (ATP) can induce PS exposure on freshly isolated human RBCs, but whether this process occurs in stored RBCs or changes during RBC aging is unknown. RBCs were processed and stored according to Australian blood banking guidelines. PS exposure was determined by annexin V binding and flow cytometry. Efficacy of P2X antagonists was assessed by flow cytometric measurements of ATP-induced ethidium+ uptake in RPMI 8226 cells. Osmotic fragility was assessed by lysis in hypotonic saline. RBCs were fractionated by discontinuous density centrifugation. ATP (1 mmol/L) induced PS exposure on RBCs stored for less than 1 week. This process was near-completely inhibited by the P2X7 antagonists A438079 and AZ10606120 and the P2X1/P2X7 antagonist MRS2159 but not the P2X1 antagonist NF499. ATP-induced PS exposure on RBCs was not dependent on K+, Na+, or Cl- fluxes. ATP did not alter the osmotic fragility of stored RBCs. ATP-induced PS exposure was similar between RBCs of different densities. ATP-induced PS exposure was also similar between RBCs stored for less than 1 week or for 6 weeks. The propensity of RBCs to undergo P2X7-mediated PS exposure does not alter during in vivo and ex vivo aging. Thus, P2X7 activation is unlikely to be involved in the removal of senescent RBCs or stored RBCs after transfusion. © 2015 AABB.

  8. Alteration in certain enzymological parameters of an Indian major carp, Cirrhinus mrigala exposed to short- and long-term exposure of clofibric acid and diclofenac.

    Science.gov (United States)

    Saravanan, Manoharan; Ramesh, Mathan; Petkam, Rakpong

    2013-12-01

    The extensive use of pharmaceuticals in human and veterinary medicine may enter the aquatic environment and pose a serious threat to non-target aquatic organisms like fish. In this study, Indian major carp Cirrhinus mrigala was exposed to different concentrations (1, 10 and 100 μg L⁻¹) of most commonly used pharmaceutical drugs clofibric acid (CA) and diclofenac (DCF) to evaluate its impacts on certain enzymological parameters during short- and long-term exposures. During short-term (96 h) exposure period, plasma glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and gill Na⁺/K⁺-ATPase activity were significantly altered at all concentrations of both the CA- and DCF-treated fish. In long-term exposure (35 days), gill Na⁺/K⁺-ATPase activity was found to be significantly increased at all concentration of CA and DCF exposures throughout the study period (except at the end of 7th day in 10 and 100 µg L⁻¹) . However, a biphasic trend was observed in plasma GOT and GPT activity when compared to the control groups. In both short- and long-term exposure, a significant (P < 0.01 and P < 0.05) changes were observed in all enzymological parameters of fish C. mrigala exposed to different concentrations of CA and DCF. The alterations of these enzymological parameters can be effectively used as potential biomarkers in monitoring of pharmaceutical toxicity in aquatic environment and organisms.

  9. Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.

    Science.gov (United States)

    Renteria, Rafael; Maier, Esther Y; Buske, Tavanna R; Morrisett, Richard A

    2017-01-01

    A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The

  10. Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

    Science.gov (United States)

    Molina, S J; Capani, F; Guelman, L R

    2016-04-01

    It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

    Science.gov (United States)

    Zhang, W; Li, Q; Deyssenroth, M; Lambertini, L; Finik, J; Ham, J; Huang, Y; Tsuchiya, K J; Pehme, P; Buthmann, J; Yoshida, S; Chen, J; Nomura, Y

    2018-04-01

    Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood. © 2018 British Society for Neuroendocrinology.

  12. Prenatal exposure to low-level methylmercury alters the child's fine motor skills at the age of 18 months.

    Science.gov (United States)

    Prpić, Igor; Milardović, Ana; Vlašić-Cicvarić, Inge; Špiric, Zdravko; Radić Nišević, Jelena; Vukelić, Petar; Snoj Tratnik, Janja; Mazej, Darja; Horvat, Milena

    2017-01-01

    To compare motor, cognitive and language characteristics in children aged 18 months who were prenatally exposed to low-level methyl-mercury (MeHg), and to analyze the eventual differences in these characteristics in relation to cord blood THg concentration. The total number of 205 child-mother pairs was included in the study, and total cord blood mercury was measured in 198 of them. Out of the 198 already measured samples, 47 of them have also been tested for methyl-mercury in cord blood. Data regarding the 47 samples of MeHg levels has been used for calculating the correlation between cord blood THg and cord blood MeHg. MeHg and THg showed a significant correlation (r=0.95, pmotor, cognitive and language skills were conducted on 168 children using The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Regarding the cord blood THg concentration, 135 children were divided in 4 quartile groups. Their neurodevelopmental characteristics have been compared. The cord blood THg concentration median and inter-quartile range was 2.98ng/g (1.41-5.61ng/g). There was a negative correlation between cord blood THg concentration and fine motor skills (rho=-0.22, p=0.01). It is evident that children grouped in 2nd ,3rd and 4th quartile had statistically significant lower fine motor skills assessment related to those grouped in 1st quartile (2nd quartile -1.24, p=0.03; 3rd quartile -1.28, p=0.03; 4th quartile -1.45, p=0.01). The differences in fine motor skills assessments between children in 2nd and 3rd and 3rd and 4th quartile were not statistically significant. Intrauterine exposure to low-level THg (MeHg) is associated with alterations in fine motor skills at the age of 18 months. Copyright © 2016. Published by Elsevier Inc.

  13. Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

    Science.gov (United States)

    Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R

    2017-05-01

    Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice

    International Nuclear Information System (INIS)

    Bardullas, U.; Limon-Pacheco, J.H.; Giordano, M.; Carrizales, L.; Mendoza-Trejo, M.S.; Rodriguez, V.M.

    2009-01-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.

  15. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  16. Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase gene expression, exploratory and motor coordination-linked behaviour in male rats.

    Science.gov (United States)

    Obajuluwa, Adejoke Olukayode; Akinyemi, Ayodele Jacob; Afolabi, Olakunle Bamikole; Adekoya, Khalid; Sanya, Joseph Olurotimi; Ishola, Azeez Olakunle

    2017-01-01

    Humans in modern society are exposed to an ever-increasing number of electromagnetic fields (EMFs) and some studies have demonstrated that these waves can alter brain function but the mechanism still remains unclear. Hence, this study sought to investigate the effect of 2.5 Ghz band radio-frequency electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA expression level as well as locomotor function and anxiety-linked behaviour in male rats. Animals were divided into four groups namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8 weeks respectively. The results revealed that WiFi exposure caused a significant increase in anxiety level and affect locomotor function. Furthermore, there was a significant decrease in AChE activity with a concomitant increase in AChE mRNA expression level in WiFi exposed rats when compared with control. In conclusions, these data showed that long term exposure to WiFi may lead to adverse effects such as neurodegenerative diseases as observed by a significant alteration on AChE gene expression and some neurobehavioral parameters associated with brain damage.

  17. Cigarette Smoke Exposure during Pregnancy Alters Fetomaternal Cell Trafficking Leading to Retention of Microchimeric Cells in the Maternal Lung

    Science.gov (United States)

    Vogelgesang, Anja; Scapin, Cristina; Barone, Caroline; Tam, Elaine

    2014-01-01

    Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans. PMID:24832066

  18. Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Burns, E. M.; Tober, K. L.; Riggenbach, J. A.; Oberyszyn, T. M.; Kusewitt, D. F.; Young, G. S.

    2013-01-01

    Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemo preventive.

  19. Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Erin M. Burns

    2013-01-01

    Full Text Available Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC development. However, the presumed effects of extended ultraviolet light B (UVB exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac or antioxidant (C E Ferulic or vitamin E compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

  20. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    Science.gov (United States)

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  1. Exposure to p,p'-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Barber, David S; McNally, Alex J; Garcia-Reyero, Natàlia; Denslow, Nancy D

    2007-02-15

    Largemouth bass (LMB) in Central Florida living on sites with high levels of organochlorine pesticides (OCPs) have exhibited poor reproductive success and altered steroid profiles. The mechanism underlying these changes is unknown, however changes in the rate of steroid metabolism could alter steroid homeostasis. Members of the CYP2 and CYP3A families play a significant role in the metabolism of many xenobiotics and endogenous compounds, including sex steroids. Therefore, the goal of this study was to identify members of the CYP2 and CYP3A families in LMB and characterize the effects of OCP exposure on their expression. Full-length clones of two CYP3A isoforms were obtained from LMB liver, CYP3A68 and 3A69, which exhibited significant sequence divergence. Full-length clones for CYP2N14 and CYP2P11 were also obtained from LMB liver. Steady-state mRNA levels of each of these CYPs increased in both sexes between early reproductive phase (December) and peak reproductive phase (March). Expression of CYP3A68 and CYP2P11 was sexually dimorphic during peak reproductive phase with 2-fold higher expression in females and males, respectively. Foodborne exposure to 46 ppm p,p'-DDE or 0.8 ppm dieldrin for 30 days did not have a significant effect on expression of CYPs. However, 4 months exposure to p,p'-DDE induced CYP3A68 and 3A69 expression in both sexes, while dieldrin produced weak induction of CYP3A68 and suppressed CYP3A69 expression in females, but had no effect on males. Neither p,p'-DDE nor dieldrin significantly altered the expression of CYP2P11 or CYP2N14. This work demonstrates that there are significant changes in CYP expression that occur during LMB reproduction which can be modified by exposure to OCPs.

  2. Exposure to p,p′-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Barber, David S.; McNally, Alex J.; Garcia-Reyero, Natàlia; Denslow, Nancy D.

    2007-01-01

    Largemouth bass (LMB) in Central Florida living on sites with high levels of organochlorine pesticides (OCPs) have exhibited poor reproductive success and altered steroid profiles. The mechanism underlying these changes is unknown, however changes in the rate of steroid metabolism could alter steroid homeostasis. Members of the CYP2 and CYP3A families play a significant role in the metabolism of many xenobiotics and endogenous compounds, including sex steroids. Therefore, the goal of this study was to identify members of the CYP2 and CYP3A families in LMB and characterize the effects of OCP exposure on their expression. Full-length clones of two CYP3A isoforms were obtained from LMB liver, CYP3A68 and 3A69, which exhibited significant sequence divergence. Full-length clones for CYP2N14 and CYP2P11 were also obtained from LMB liver. Steady-state mRNA levels of each of these CYPs increased in both sexes between early reproductive phase (December) and peak reproductive phase (March). Expression of CYP3A68 and CYP2P11 was sexually dimorphic during peak reproductive phase with 2-fold higher expression in females and males, respectively. Foodborne exposure to 46 ppm p,p′-DDE or 0.8 ppm dieldrin for 30 days did not have a significant effect on expression of CYPs. However, 4 months exposure to p,p′-DDE induced CYP3A68 and 3A69 expression in both sexes, while dieldrin produced weak induction of CYP3A68 and suppressed CYP3A69 expression in females, but had no effect on males. Neither p,p′-DDE nor dieldrin significantly altered the expression of CYP2P11 or CYP2N14. This work demonstrates that there are significant changes in CYP expression that occur during LMB reproduction which can be modified by exposure to OCPs. PMID:17145087

  3. Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.

    Science.gov (United States)

    Veazey, Kylee J; Wang, Haiqing; Bedi, Yudhishtar S; Skiles, William M; Chang, Richard Cheng-An; Golding, Michael C

    2017-05-01

    Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program. To address this question, we examined the impact of ethanol exposure in mouse embryonic stem cells cultured under 2i conditions, where the transcriptional program is rigidly enforced through the use of small molecule inhibitors. We find that ethanol-induced changes in post-translational histone modifications are dose-dependent, unique to the chromatin modification under investigation, and that the extent and direction of the change differ between the period of exposure and the recovery phase. Similar to in vivo models, we find post-translational modifications affecting histone 3 lysine 9 are the most profoundly impacted, with the signature of exposure persisting long after alcohol has been removed. These changes in chromatin structure associate with dose-dependent alterations in the levels of transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin template do not consistently associate with changes in gene transcription, impede the process of differentiation, or affect the acquisition of monoallelic patterns of expression for the imprinted gene Igf2R. These findings question the inferred universal relevance of epigenetic changes induced by drugs of abuse and suggest that changes

  4. Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3−/− mice, but not wildtype mice

    Science.gov (United States)

    Martynhak, Bruno Jacson; Hogben, Alexandra L.; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N.; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R.

    2017-01-01

    Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are ‘direct’ effects of light on affect, an ‘indirect’ pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3−/− mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3−/−) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2–3 of dim light at night, whereas WT mice did not. Per3−/− mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3−/− nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3−/− phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light. PMID:28071711

  5. Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice.

    Science.gov (United States)

    Martynhak, Bruno Jacson; Hogben, Alexandra L; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R

    2017-01-10

    Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3 -/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3 -/- ) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3 -/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3 -/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3 -/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.

  6. Sound production in Japanese medaka (Oryzias latipes) and its alteration by exposure to aldicarb and copper sulfate.

    Science.gov (United States)

    Kang, Ik Joon; Qiu, Xuchun; Moroishi, Junya; Oshima, Yuji

    2017-08-01

    This study is the first to report sound production in Japanese medaka (Oryzias latipes). Sound production was affected by exposure to the carbamate insecticide (aldicarb) and heavy-metal compound (copper sulfate). Medaka were exposed at four concentrations (aldicarb: 0, 0.25, 0.5, and 1 mg L -1 ; copper sulfate: 0, 0.5, 1, and 2 mg L -1 ), and sound characteristics were monitored for 5 h after exposure. We observed constant average interpulse intervals (approx 0.2 s) in all test groups before exposure, and in the control groups throughout the experiment. The average interpulse interval became significantly longer during the recording periods after 50 min of exposure to aldicarb, and reached a length of more than 0.3 s during the recording periods after 120 min exposure. Most medaka fish stopped to produce sound after 50 min of exposure to copper sulfate at 1 and 2 mg L -1 , resulting in significantly declined number of sound pulses and pulse groups. Relative shortened interpulse intervals of sound were occasionally observed in medaka fish exposed to 0.5 mg L -1 copper sulfate. These alternations in sound characteristics due to toxicants exposure suggested that they might impair acoustic communication of medaka fish, which may be important for their reproduction and survival. Our results suggested that using acoustic changes of medaka has potential to monitor precipitate water pollutions, such as intentional poisoning or accidental leakage of industrial waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    International Nuclear Information System (INIS)

    Sekizawa, Shin-ichi; Joad, Jesse P.; Pinkerton, Kent E.; Bonham, Ann C.

    2010-01-01

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  8. Exposures involving perturbations of the EM field have non-linear effects on radiation response and can alter the expression of radiation induced bystander effects

    Science.gov (United States)

    Mothersill, Carmel; Seymour, Colin

    2012-07-01

    Our recent data suggest there is a physical component to the bystander signal induced by radiation exposure and that alternative medicine techniques such as Reiki and acupuncture or exposures to weak EM fields alter the response of cells to direct irradiation and either altered bystander signal production or altered the response of cells receiving bystander signals. Our proposed mechanism to explain these findings is that perturbation of electromagnetic (EM) fields is central to the induction of low radiation dose responses especially non-targeted bystander effects. In this presentation we review the alternative medicine data and other data sets from our laboratory which test our hypothesis that perturbation of bio-fields will modulate radiation response in the low dose region. The other data sets include exposure to MRI, shielding using lead and or Faraday cages, the use of physical barriers to bystander signal transmission and the use of membrane channel blockers. The data taken together strongly suggest that EM field perturbation can modulate low dose response and that in fact the EM field rather than the targeted deposition of ionizing energy in the DNA may be the key determinant of dose response in a cell or organism The results also lead us to suspect that at least when chemical transmission is blocked, bystander signals can be transmitted by other means. Our recent experiments suggest light signals and volatiles are not likely. We conclude that alternative medicine and other techniques involving electromagnetic perturbations can modify the response of cells to low doses of ionizing radiation and can induce bystander effects similar to those seen in medium transfer experiments. In addition to the obvious implications for mechanistic studies of low dose effects, this could perhaps provide a novel target to exploit in space radiation protection and in optimizing therapeutic gain during radiotherapy.

  9. Oxidative impairment and histopathological alterations in kidney and brain of mice following subacute lambda-cyhalothrin exposure.

    Science.gov (United States)

    Pawar, Nitin Nanasaheb; Badgujar, Prarabdh Chandrakant; Sharma, Laxman Prasad; Telang, Avinash Gopal; Singh, Karam P

    2017-03-01

    Lambda cyhalothrin (LCT), a broad-spectrum type II (α-cyano) synthetic pyrethroid pesticide, is widely employed in various agricultural and animal husbandry practices for the control of pests. Acute and chronic exposure to LCT can elicit several adverse effects including oxidative stress. With the objective to investigate nephrotoxicity and neurotoxicity of LCT in mice, we evaluated oxidative stress parameters and histological changes in the kidney and brain of LCT exposed mice. Swiss albino mice were divided randomly into four groups ( n = 6 per group) as: (A) corn oil/vehicle control; (B) 0.5 mg/kg body weight (b.w.) LCT; (C) 1 mg/kg b.w. LCT; (D) 2 mg/kg b.w. LCT. Mice were treated orally for 28 days. LCT exposure significantly increased serum urea nitrogen, creatinine and urea levels. LCT exposure also increased lipid peroxidation, superoxide anion generation, nitrite level and decreased the level of reduced glutathione. The activities of superoxide dismutase, catalase and glutathione- S-transferase were depleted significantly in both kidney and brain. Histological examination revealed marked histopathological changes in the kidney and brain of mice that were more pronounced at high dose of LCT. Thus, results of the present study indicate that 28 days oral exposure of LCT causes oxidative damage to the kidney and brain of mice which in turn could be responsible for nephrotoxicity and neurotoxicity. Nevertheless, further detailed studies are required to prove these effects especially after long-term exposure.

  10. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Aluru, Neelakanteswar; Kuo, Elaine; Helfrich, Lily W.; Karchner, Sibel I.; Linney, Elwood A.; Pais, June E.; Franks, Diana G.

    2015-01-01

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  11. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Aluru, Neelakanteswar, E-mail: naluru@whoi.edu [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Kuo, Elaine [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Stanford University, 450 Serra Mall, Stanford, CA 94305 (United States); Helfrich, Lily W. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Northwestern University, 633 Clark St, Evanston, IL 60208 (United States); Karchner, Sibel I. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Linney, Elwood A. [Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710 (United States); Pais, June E. [New England Biolabs, 240 County Road, Ipswich, MA 01938 (United States); Franks, Diana G. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2015-04-15

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  12. Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica L. Bolton

    2017-05-01

    Full Text Available Microglia are the resident immune cells of the brain, important for normal neural development in addition to host defense in response to inflammatory stimuli. Air pollution is one of the most pervasive and harmful environmental toxicants in the modern world, and several large scale epidemiological studies have recently linked prenatal air pollution exposure with an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD. Diesel exhaust particles (DEP are a primary toxic component of air pollution, and markedly activate microglia in vitro and in vivo in adult rodents. We have demonstrated that prenatal exposure to DEP in mice, i.e., to the pregnant dams throughout gestation, results in a persistent vulnerability to behavioral deficits in adult offspring, especially in males, which is intriguing given the greater incidence of ASD in males to females (∼4:1. Moreover, there is a striking upregulation of toll-like receptor (TLR 4 gene expression within the brains of the same mice, and this expression is primarily in microglia. Here we explored the impact of gestational exposure to DEP or vehicle on microglial morphology in the developing brains of male and female mice. DEP exposure increased inflammatory cytokine protein and altered the morphology of microglia, consistent with activation or a delay in maturation, only within the embryonic brains of male mice; and these effects were dependent on TLR4. DEP exposure also increased cortical volume at embryonic day (E18, which switched to decreased volume by post-natal day (P30 in males, suggesting an impact on the developing neural stem cell niche. Consistent with this hypothesis, we found increased microglial-neuronal interactions in male offspring that received DEP compared to all other groups. Taken together, these data suggest a mechanism by which prenatal exposure to environmental toxins may affect microglial development and long-term function, and thereby contribute

  13. Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control or 6% (vol/vol ethanol (EtOH throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult or 15 months (Aged of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

  14. Developmental exposure to second-hand smoke increases adult atherogenesis and alters mitochondrial DNA copy number and deletions in apoE(-/- mice.

    Directory of Open Access Journals (Sweden)

    Jessica L Fetterman

    Full Text Available Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m(3 total suspended particulate of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i in utero from gestation days 1-19, or (ii from birth until 3 weeks of age (neonatal. Subsequently, all animals were exposed to filtered air and sacrificed at 12-14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis.

  15. Developmental exposure to second-hand smoke increases adult atherogenesis and alters mitochondrial DNA copy number and deletions in apoE(-/-) mice.

    Science.gov (United States)

    Fetterman, Jessica L; Pompilius, Melissa; Westbrook, David G; Uyeminami, Dale; Brown, Jamelle; Pinkerton, Kent E; Ballinger, Scott W

    2013-01-01

    Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m(3) total suspended particulate) of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i) in utero from gestation days 1-19, or (ii) from birth until 3 weeks of age (neonatal). Subsequently, all animals were exposed to filtered air and sacrificed at 12-14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis.

  16. Developmental Exposure to Second-Hand Smoke Increases Adult Atherogenesis and Alters Mitochondrial DNA Copy Number and Deletions in apoE−/− Mice

    Science.gov (United States)

    Fetterman, Jessica L.; Pompilius, Melissa; Westbrook, David G.; Uyeminami, Dale; Brown, Jamelle; Pinkerton, Kent E.; Ballinger, Scott W.

    2013-01-01

    Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m3 total suspended particulate) of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i) in utero from gestation days 1–19, or (ii) from birth until 3 weeks of age (neonatal). Subsequently, all animals were exposed to filtered air and sacrificed at 12–14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis. PMID:23825571

  17. Modulation of estrogenic exposure effects via alterations in salinity and dissolved oxygen in male fathead minnows, Pimephales promelas

    Science.gov (United States)

    Laboratory exposure data indicate that estrogens and estrogen mimics can cause endocrine disruption in male fathead minnows (Pimephales promelas). In the wild, conditions are not static as is often the case in the laboratory. Changes in water quality parameters, such as salinity influx due to road s...

  18. Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure

    Science.gov (United States)

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Sponta...

  19. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Hannon, Patrick, E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  20. Microbes and masculinity: Does exposure to pathogenic cues alter women’s preferences for male facial masculinity and beardedness?

    Science.gov (United States)

    McIntosh, Toneya L.; Lee, Anthony J.; Sidari, Morgan J.; Stower, Rebecca E.; Sherlock, James M.

    2017-01-01

    Women’s preferences for men’s androgen dependent secondary sexual traits are proposed to be phenotypically plastic in response to exposure to pathogens and pathogen disgust. While previous studies report that masculinity in facial shape is more attractive to women who have recently been exposed to pathogenic cues and who are high in self-reported pathogen disgust, facial hair may reduce male attractiveness under conditions of high pathogens as beards are a possible breeding ground for disease carrying ectoparasites. In the present study, we test whether women’s preferences for beardedness and facial masculinity vary due to exposure to different pathogenic cues. Participants (N = 688, mean age + 1SD = 31.94 years, SD = 6.69, range = 18–67) rated the attractiveness of facial composite stimuli of men when they were clean-shaven or fully bearded. These stimuli were also manipulated in order to vary sexual dimorphism by ±50%. Ratings were conducted before and after exposure to one of four experimental treatments in which participants were primed to either high pathogens (e.g. infected cuts), ectoparasites (e.g. body lice), a mixture of pathogens and ectoparasites, or a control condition (e.g. innocuous liquids). Participants then completed the three-domain disgust scale measuring attitudes to moral, sexual and pathogen disgust. We predicted that women would prefer facial masculinity following exposure to pathogenic cues, but would show reduced preferences for facial hair following exposure to ectoparasites. Women preferred full beards over clean-shaven faces and masculinised over feminised faces. However, none of the experimental treatments influenced the direction of preferences for facial masculinity or beardedness. We also found no association between women’s self-reported pathogen disgust and their preferences for facial masculinity. However, there was a weak positive association between moral disgust scores and preferences for facial masculinity, which

  1. Metabolomic analysis of alterations in lipid oxidation, carbohydrate and amino acid metabolism in dairy goats caused by exposure to Aflotoxin B1.

    Science.gov (United States)

    Cheng, Jianbo; Huang, Shuai; Fan, Caiyun; Zheng, Nan; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

    2017-11-01

    The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, β-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.

  2. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

    Directory of Open Access Journals (Sweden)

    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

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

    Directory of Open Access Journals (Sweden)

    Nicole L. Johnson

    2011-06-01

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

  4. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    Science.gov (United States)

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2017-09-01

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  5. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Partial shading of Cabernet Sauvignon and Shiraz vines altered wine color and mouthfeel attributes, but increased exposure had little impact.

    Science.gov (United States)

    Joscelyne, Venetia L; Downey, Mark O; Mazza, Marica; Bastian, Susan E P

    2007-12-26

    Few studies have investigated the impact of vine shading on the sensory attributes of the resultant wine. This study examines the effects of canopy exposure levels on phenolic composition plus aroma, flavor, and mouthfeel aspects in wine. Wines were made from Cabernet Sauvignon and Shiraz grapes (Vitis vinifera L.) subjected to different levels of canopy exposure in a commercial vineyard in the Sunraysia region, Victoria, Australia. Canopy exposure treatments included control (standard vineyard practice), exposed (achieved with a foliage wire 600 mm above the top cordon), highly exposed (using a foliage wire with leaf plucking in the fruit zone), and shaded treatment (using 70% shade-cloth). Spectral and descriptive analyses showed that levels of anthocyanins, other phenolics, and perceived astringency were lower in wines made from shaded fruit; however, the reverse was generally not observed in wines of exposed and highly exposed fruit. Descriptive analysis also showed wines from the shaded fruit were different from other treatments for a number of flavor and aroma characters. These findings have implications for vineyard management practices.

  7. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  8. Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Daniela Sarahí Gutiérrez-Torres

    2015-01-01

    Full Text Available Inorganic arsenic (iAs exposure induces a decrease in glucose type 4 transporter (GLUT4 expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2 exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n=15 were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P<0.01 and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P<0.05 in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.

  9. Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Jarrar Bashir M

    2011-09-01

    Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

  10. Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain.

    Science.gov (United States)

    Lee, Min-Young; Yu, Ji Hea; Kim, Ji Yeon; Seo, Jung Hwa; Park, Eun Sook; Kim, Chul Hoon; Kim, Hyongbum; Cho, Sung-Rae

    2013-01-01

    Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+ / Cl- -dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

  11. Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes

    International Nuclear Information System (INIS)

    Han, Longzhe; Itoh, Kyoko; Yaoi, Takeshi; Moriwaki, Sanzo; Kato, Shingo; Nakamura, Keiko; Fushiki, Shinji

    2011-01-01

    It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection

  12. Chronic dietary mercury exposure causes oxidative stress, brain lesions, and altered behaviour in Atlantic salmon (Salmo salar) parr

    International Nuclear Information System (INIS)

    Berntssen, Marc H.G.; Aatland, Aase; Handy, Richard D.

    2003-01-01

    Atlantic salmon (Salmo salar L.) parr were fed for 4 months on fish meal based diets supplemented with mercuric chloride (0, 10, or 100 mg Hg kg -1 DW) or methylmercury chloride (0, 5, or 10 mg Hg kg -1 DW) to assess the effects of inorganic (Hg) and organic dietary mercury on brain lipid peroxidation and neurotoxicity. Lipid peroxidative products, endogenous anti oxidant enzymes, brain histopathology, and overall behaviour were measured. Methylmercury accumulated significantly in the brain of fish fed 5 or 10 mg kg -1 by the end of the experiment, and inorganic mercury accumulated significantly in the brain only at 100 mg kg -1 exposure levels. No mortality or growth reduction was observed in any of the exposure groups. Fish fed 5 mg kg -1 methylmercury had a significant increase (2-fold) in the antioxidant enzyme super oxide dismutase (SOD) in the brain. At dietary levels of 10 mg kg -1 methylmercury, a significant increase (7-fold) was observed in lipid peroxidative products (thiobarbituric acid reactive substances, TBARS) and a subsequently decrease (1.5-fold) in anti oxidant enzyme activity (SOD and glutathione peroxidase, GSH-Px). Fish fed 10 mg kg -1 methylmercury also had pathological damage (vacoulation and necrosis), significantly reduced neural enzyme activity (5-fold reduced monoamine oxidase, MAO, activity), and reduced overall post-feeding activity behaviour. Pathological injury started in the brain stem and became more widespread in other areas of the brain at higher exposure levels. Fish fed 100 mg Hg kg -1 inorganic mercury had significant reduced neural MAO activity and pathological changes (astrocyte proliferation) in the brain, however, neural SOD and GSH-Px enzyme activity, lipid peroxidative products (TBARS), and post feeding behaviour did not differ from controls. Compared with other organs, the brain is particular susceptible for dietary methylmercury induced lipid peroxidative stress at relative low exposure concentrations. Doses of dietary

  13. Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates

    Energy Technology Data Exchange (ETDEWEB)

    Rabovsky, J.; Judy, D.J.; Rodak, D.J.; Petersen, M.

    1986-06-01

    We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under conditions of particulate exposure and virus infection, serum IFN levels peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE.

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

    International Nuclear Information System (INIS)

    Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.; Napoli, Joseph L.; Olson, James R.

    2007-01-01

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

  15. Quantitative proteomics of heavy metal exposure in Arabidopsis thaliana reveals alterations in one-carbon metabolism enzymes upon exposure to zinc.

    Science.gov (United States)

    Barkla, Bronwyn J; Vera-Estrella, Rosario; Miranda-Vergara, María Cristina; Pantoja, Omar

    2014-12-05

    Plant zinc (Zn) homeostasis must be tightly regulated as the requirement for this micronutrient necessitates its uptake. However, excessive Zn can lead to toxicity and the plant must respond rapidly and effectively within its capacity to minimize damage. To detect mechanisms that may be important for coping with excess Zn we carried out a quantitative proteomics approach using 2D-DIGE to identify Zn-responsive proteins in microsomal fractions from leaves of 4day, 200μM Zn-treated, Arabidopsis thaliana plants. Of the eight proteins which showed significant changes in abundance in the Zn-treated samples and which met all of the selection criteria following statistical analysis, six were successfully identified by LC-MS/MS with 2 or more unique peptides. Three of the proteins were found to be involved in the one-carbon metabolism pathway; including glycine decarboxylase P protein, serine hydroxymethyltransferase (SHMT) and methionine synthase, all of which showed reduced abundance in the Zn-treated samples. Western blot analysis confirmed the decrease in SHMT, while changes in metal tolerance protein indicated plants were most likely actively sequestering Zn. Interestingly, excess Zn led to increased petiole length, a phenotype which may reflect the reduced levels of methionine, a key product of the one-carbon metabolism pathway. Metal contamination is becoming an increasingly common environmental problem. High levels of zinc can be found in certain soils naturally or as a result of long-term anthropogenic activity which leads to its accumulation; i.e. use of fertilizers or industrial waste. The study of metal tolerant plants, particularly those classified as hyperaccumulators has been driven by the potential use of these plants for bioremediation purposes. However, the effects of heavy metal exposure on sensitive plants and the different cellular processes that are affected have received significantly less attention. We are interested in identifying proteins in A

  16. Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats.

    Science.gov (United States)

    Ahmadalipour, A; Sadeghzadeh, J; Vafaei, A A; Bandegi, A R; Mohammadkhani, R; Rashidy-Pour, A

    2015-10-01

    Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF

  17. Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams

    Science.gov (United States)

    Meyer, Erik; Eagles-Smith, Collin A.; Sparling, Donald; Blumenshine, Steve

    2014-01-01

    Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

  18. Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams.

    Science.gov (United States)

    Meyer, Erik; Eagles-Smith, Collin A; Sparling, Donald; Blumenshine, Steve

    2014-01-01

    Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

  19. Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption.

    Science.gov (United States)

    Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

    2013-12-01

    Exposure to environmental chemicals known as endocrine disruptors (EDs) is in many cases associated with an unpredictable hazard for wildlife and human health. The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable ED assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17α-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

    Institute of Scientific and Technical Information of China (English)

    LI SUN; ZHENG-YAN ZHAO; JIAN HU; XIE-LAI ZHOU

    2005-01-01

    Objective Chronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.Methods Sixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%,0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075%group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3)NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01). Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

  1. Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism.

    Science.gov (United States)

    Darnall, Robert A; Chen, Xi; Nemani, Krishnamurthy V; Sirieix, Chrystelle M; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L; Hunt, Carl E

    2017-07-01

    BackgroundPreterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury.MethodsRat pups were exposed to IH from P2 to P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20-P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed.ResultsPups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus, and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr, and Gly/Cr; increases in TCho and GPC in the brainstem; and decreases in NAA/Cho in the hippocampus.ConclusionsWe conclude that early postnatal exposure to IH, similar in magnitude to that experienced in human preterm infants, is associated with evidence for proinflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia.

  2. Morphological alterations in the freshwater rotifer Brachionus calyciflorus Pallas 1766 (Rotifera: Monogononta) caused by vinclozolin chronic exposure.

    Science.gov (United States)

    Alvarado-Flores, Jesús; Rico-Martínez, Roberto; Adabache-Ortíz, Araceli; Silva-Briano, Marcelo

    2015-05-01

    Vinclozolin (VZ) is a dicarboximide fungicide widely used on fruits, vegetables and wines, effective against fungi plagues. In this study we characterized the effects of VZ using a 4-day reproductive chronic assay with the freshwater rotifer Brachionus calyciflorus. The assay included observations of several features of asexual and sexual reproduction. Our results indicate that VZ: (a) increased asexual and sexual reproduction, (b) caused severe abnormality in females and (c) these abnormalities were inherited by sexual and asexual reproduction. At 1.2 mg/L three abnormal females were found out of 457 total females (0.66 %). This low percentage is consistent and reproducible according to further analysis, where we increased the number of replicates and total females exposed to 1.2 mg/L of VZ, and found 18 abnormal females out of 2868 total females (0.63 % abnormality). Interestingly, abnormal females found at 5.6 mg/L VZ exposure, were able to show mating behavior. Our results suggest that VZ behaves as a strong endocrine disruptor whose effects show the characteristic inverted-U-shape exposure concentration response curve regarding the intrinsic population increase and the percentage of abnormalities as endpoints.

  3. Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

    Science.gov (United States)

    Dulka, Eden A; Moenter, Suzanne M

    2017-11-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

  4. Acute Exposure to Fluoxetine Alters Aggressive Behavior of Zebrafish and Expression of Genes Involved in Serotonergic System Regulation

    Directory of Open Access Journals (Sweden)

    Michail Pavlidis

    2017-04-01

    Full Text Available Zebrafish, Danio rerio, is an emerging model organism in stress and neurobehavioral studies. In nature, the species forms shoals, yet when kept in pairs it exhibits an agonistic and anxiety-like behavior that leads to the establishment of dominant-subordinate relationships. Fluoxetine, a selective serotonin reuptake inhibitor, is used as an anxiolytic tool to alter aggressive behavior in several vertebrates and as an antidepressant drug in humans. Pairs of male zebrafish were held overnight to develop dominant—subordinate behavior, either treated or non-treated for 2 h with fluoxetine (5 mg L−1, and allowed to interact once more for 1 h. Behavior was recorded both prior and after fluoxetine administration. At the end of the experiment, trunk and brain samples were also taken for cortisol determination and mRNA expression studies, respectively. Fluoxetine treatment significantly affected zebrafish behavior and the expression levels of several genes, by decreasing offensive aggression in dominants and by eliminating freezing in the subordinates. There was no statistically significant difference in whole-trunk cortisol concentrations between dominant and subordinate fish, while fluoxetine treatment resulted in higher (P = 0.004 cortisol concentrations in both groups. There were statistically significant differences between dominant and subordinate fish in brain mRNA expression levels of genes involved in stress axis (gr, mr, neural activity (bdnf, c-fos, and the serotonergic system (htr2b, slc6a4b. The significant decrease in the offensive and defensive aggression following fluoxetine treatment was concomitant with a reversed pattern in c-fos expression levels. Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles.

  5. Prenatal binge-like alcohol exposure alters brain and systemic responses to reach sodium and water balance.

    Science.gov (United States)

    Godino, A; Abate, P; Amigone, J L; Vivas, L; Molina, J C

    2015-12-17

    The aim of the present work is to analyze how prenatal binge-like ethanol exposure to a moderate dose (2.0 g/kg; group Pre-EtOH) during gestational days (GD) 17-20 affects hydroelectrolyte regulatory responses. This type of exposure has been observed to increase ethanol consumption during adolescence (postnatal day 30-32). In this study we analyzed basal brain neural activity and basal-induced sodium appetite (SA) and renal response stimulated by sodium depletion (SD) as well as voluntary ethanol consumption as a function of vehicle or ethanol during late pregnancy. In adolescent offspring, SD was induced by furosemide and a low-sodium diet treatment (FURO+LSD). Other animals were analyzed in terms of immunohistochemical detection of Fra-like (Fra-LI-ir) protein and serotonin (5HT) and/or vasopressin (AVP). The Pre-EtOH group exhibited heightened voluntary ethanol intake and a reduction in sodium and water intake induced by SD relative to controls. Basal Na and K concentrations in urine were also reduced in Pre-EtOH animals while the induced renal response after FURO treatment was similar across prenatal treatments. However, the correlation between urine volume and water intake induced by FURO significantly varied across these treatments. At the brain level of analysis, the number of basal Fra-LI-ir was significantly increased in AVP magnocellular neurons of the paraventricular nucleus (PVN) and in 5HT neurons in the dorsal raphe nucleus (DRN) in Pre-EtOH pups. In the experimental group, we also observed a significant increase in Fra-LI along the nucleus of the solitary tract (NTS) and in the central extended amygdala nuclei. In summary, moderate Pre-EtOH exposure produces long-lasting changes in brain organization, affecting basal activity of central extended amygdala nuclei, AVP neurons and the inhibitory areas of SA such as the NTS and the 5HT-DRN. These changes possibly modulate the above described variations in basal-induced drinking behaviors and renal

  6. Early-Life Exposure to Antibiotics, Alterations in the Intestinal Microbiome, and Risk of Metabolic Disease in Children and Adults.

    Science.gov (United States)

    Yallapragada, Sushmita G; Nash, Colleen B; Robinson, Daniel T

    2015-11-01

    The intestinal microbiome is a complex ecosystem of microorganisms that colonize the human gastrointestinal tract. The microbiome evolves rapidly in early life with contributions from diet, genetics and immunomodulatory factors. Changes in composition of the microbiota due to antibiotics may lead to negative long-term effects including obesity and diabetes mellitus, as evidenced by both animal and large human studies. Inappropriate exposures to antibiotics occur frequently in early childhood. Therefore, an evidence-based system of antimicrobial use should be employed by all providers, especially those who care for pediatric patients. This article explores the natural evolution of the intestinal microbiome from the perinatal period into early childhood, the effect of antibiotics on the microbial ecology, and the implications for future health and disease. Copyright 2015, SLACK Incorporated.

  7. Exposure of Cucurbita pepo to DDE-contamination alters the endophytic community: A cultivation dependent vs a cultivation independent approach

    International Nuclear Information System (INIS)

    Eevers, N.; Hawthorne, J.R.; White, J.C.; Vangronsveld, J.; Weyens, N.

    2016-01-01

    2,2-bis(p-chlorophenyl)-1,1-dichloro-ethylene (DDE) is the most abundant and persistent degradation product of the pesticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is encountered in contaminated soils worldwide. Both DDE and DDT are classified as Persistent Organic Pollutants (POPs) due to their high hydrophobicity and potential for bioaccumulation and biomagnification in the food chain. Zucchini (Cucurbita pepo ssp. pepo) has been shown to accumulate high concentrations of DDE and other POPs and has been proposed as a phytoremediation tool for contaminated soils. The endophytic bacteria associated with this plant may play an important role in the remedial process. Therefore, this research focuses on changes in endophytic bacterial communities caused by the exposure of C. pepo to DDE. The total bacterial community was investigated using cultivation-independent 454 pyrosequencing, while the cultivable community was identified using cultivation-dependent isolation procedures. For both procedures, increasing numbers of endophytic bacteria, as well as higher diversities of genera were observed when plants were exposed to DDE. Several bacterial genera such as Stenotrophomonas sp. and Sphingomonas sp. showed higher abundance when DDE was present, while, for example Pseudomonas sp. showed a significantly lower abundance in the presence of DDE. These findings suggest tolerance of different bacterial strains to DDE, which might be incorporated in further investigations to optimize phytoremediation with the possible use of DDE-degrading endophytes. - Highlights: • Cucurbita pepo accumulates DDE and can be used for phytoremediation. • Phytoremediation capacity might be enhanced with endophytic bacteria. • The differences in bacterial communities without and with DDE are investigated. • Several DDE-tolerant bacteria are discovered and might be used in phytoremediation. - DDE-exposure and DDE-uptake of Cucurbita pepo lead to increases in both diversity

  8. Ozone exposure alters temporal fluctuations of 14C-labeled assimilate pools in leaves of Pinus taeda L

    International Nuclear Information System (INIS)

    Friend, A.L.; Tomlinson, P.T.

    1991-01-01

    The effects of O 3 on uptake and distribution of 14 C within current-year foliage of 3-year-old loblolly pine (Pinus taeda L.) seedlings were studied using open-top exposure chambers that delivered ozone at three concentrations: sub-ambient O 3 [charcoal-filtered air (CF)]; ambient O 3 (AMB); and twice-ambient O 3 (2X). Seedlings were exposed to O 3 from May to Oct. of 1987, 1988, and 1989. In July, Aug., and Sept. 1989, individual foliage fascicles were labeled with 14 CO 2 ; harvested at 0, 0.5, 4, 24, and 48h after labeling; and analyzed for 14 C in lipids and pigments, protein, starch, residue, sugars, organic acids, and amino acids. O 3 affected initial (0 h) incorporation of 14 C into different chemical fractions, and the relative distribution of 14 C among fractions at specific points in time. Starch dynamics were particularly responsive to and negatively affected by O 3 . In 2X treatments, only 39-46% of the initial (0 h) 14 C incorporated into starch remained after 48h, compared with a range of 56-90% remaining in CF treatments. The percentage of 14 C in the starch fraction after 48 h decreased by nearly three-fold in August from CF to 2X treatments [%total 14 C in starch: 31% (CF), 17% (AMB), and 11% (2X)]. The authors data indicated that foliar starch synthesis and/or retention was depressed by ozone exposure during late-season months, and supported the concept that O 3 decreases growth by depleting carbohydrate reserves. Other findings will be discussed

  9. Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

    Science.gov (United States)

    Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

    2018-01-01

    With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified

  10. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    Directory of Open Access Journals (Sweden)

    Patil NA

    2016-09-01

    Full Text Available Nayana A Patil,1,2 WN Gade,2 Deepti D Deobagkar1 1Department of Zoology, Molecular Biology Research Laboratory, Centre of Advanced Studies, 2Department of Biotechnology, Proteomic Research Laboratory, Savitribai Phule Pune University, Pune, India Abstract: Titanium dioxide (TiO2 and zinc oxide (ZnO nanoparticles (NPs are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5 cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear

  11. Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.

    Directory of Open Access Journals (Sweden)

    Ihssane Zouikr

    Full Text Available Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis during postnatal day (PND 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG as well as rostral and caudal axes of the ventrolateral PAG (VLPAG. Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb as compared to medial habenula (MHb, however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

  12. Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

    Science.gov (United States)

    Zouikr, Ihssane; James, Morgan H.; Campbell, Erin J.; Clifton, Vicki L.; Beagley, Kenneth W.; Dayas, Christopher V.; Hodgson, Deborah M.

    2014-01-01

    Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. PMID:24878577

  13. Noise exposure alters long-term neural firing rates and synchrony in primary auditory and rostral belt cortices following bimodal stimulation.

    Science.gov (United States)

    Takacs, Joseph D; Forrest, Taylor J; Basura, Gregory J

    2017-12-01

    We previously demonstrated that bimodal stimulation (spinal trigeminal nucleus [Sp5] paired with best frequency tone) altered neural tone-evoked and spontaneous firing rates (SFRs) in primary auditory cortex (A1) 15 min after pairing in guinea pigs with and without noise-induced tinnitus. Neural responses were enhanced (+10 ms) or suppressed (0 ms) based on the bimodal pairing interval. Here we investigated whether bimodal stimulation leads to long-term (up to 2 h) changes in tone-evoked and SFRs and neural synchrony (correlate of tinnitus) and if the long-term bimodal effects are altered following noise exposure. To obviate the effects of permanent hearing loss on the results, firing rates and neural synchrony were measured three weeks following unilateral (left ear) noise exposure and a temporary threshold shift. Simultaneous extra-cellular single-unit recordings were made from contralateral (to noise) A1 and dorsal rostral belt (RB); an associative auditory cortical region thought to influence A1, before and after bimodal stimulation (pairing intervals of 0 ms; simultaneous Sp5-tone and +10 ms; Sp5 precedes tone). Sixty and 120 min after 0 ms pairing tone-evoked and SFRs were suppressed in sham A1; an effect only preserved 120 min following pairing in noise. Stimulation at +10 ms only affected SFRs 120 min after pairing in sham and noise-exposed A1. Within sham RB, pairing at 0 and +10 ms persistently suppressed tone-evoked and SFRs, while 0 ms pairing in noise markedly enhanced tone-evoked and SFRs up to 2 h. Together, these findings suggest that bimodal stimulation has long-lasting effects in A1 that also extend to the associative RB that is altered by noise and may have persistent implications for how noise damaged brains process multi-sensory information. Moreover, prior to bimodal stimulation, noise damage increased neural synchrony in A1, RB and between A1 and RB neurons. Bimodal stimulation led to persistent changes in neural synchrony in

  14. Cyto-architectural Alterations in the Corpuscles of Stannius of Stinging Catfish Heteropneustes fossilis after Exposure to a Botanical Pesticide (Nerium indicum

    Directory of Open Access Journals (Sweden)

    ManiRam Prasad

    2014-03-01

    Full Text Available Background: This investigation describes the cyto-architectural alterations observed in the corpuscles of Stannius of stinging catfish Heteropneustes fossilis after treatment with a botanical pesticide Nerium indicum. Methods: Heteropneustes fossilis were subjected to 11.27 and 2.81 mg/L of Nerium indicum leaf extract over short- and long-term exposure periods, respectively. Blood was collected for calcium analysis and corpuscles of Stannius (CS gland were fixed on 24, 48, 72 and 96 h in the short-term experiment and after 7, 14, 21, and 28 days in the long-term experiment. Results: Serum calcium levels decreased from 48 h to 96 h. CS remains unaffected till 72 h. After the 96-hour treatment, increased granulation was observed in AF- positive cells. Nuclear volume of these cells exhibited no change throughout the short-term treatment. Slight increases in nuclear volume of AF-negative cells were recorded after 96 h. Nerium indicum caused decreases in serum calcium levels of H. fossilis from day 14 to 28. CS exhibited no alterations up to 14 days of exposure. AF-positive cells of CS depicted increased granulation after 21 days of treatment. Nuclear volume of these cells exhibited a slight decrease from day 21 to 28. Heavy accumulation of AF-positive granules was observed and few degenerating cells were noticed. Nuclear volume of AF-negative cells increased after 21 and 28 days of treatment. Vacuolization and degeneration occurred in certain places. Conclusion: It is inferred from the present study that the botanical pesticide Nerium indicum induced severe changes in the corpuscles of Stannius of catfish.

  15. The DNA methylation status alteration of two steroidogenic genes in gonads of rare minnow after bisphenol A exposure.

    Science.gov (United States)

    Zhang, Ting; Liu, Yan; Chen, Hong; Gao, Jiancao; Zhang, Yingying; Yuan, Cong; Wang, Zaizhao

    2017-08-01

    Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play important roles in steroid biosynthesis. According to our previous studies, bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation is barely understood. In the present study, aiming to explore how BPA affects the mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1 and their mRNA expression levels. Results showed that exposure to BPA significantly increased serum estradiol (E2) and 11-ketotesterone (11-KT) concentrations. Ovarian mRNA expression of cyp17a1 and cyp11a1 were significantly decreased after BPA exposure 7- for and 14-days. However, transcriptions of testicular cyp17a1 and cyp11a1 were significantly increased and decreased respectively after BPA treatment for 14days. The DNA methylation levels of cyp17a1 were decreased in ovaries on day 7 and increased in ovaries and decreased in testes respectively on day 14. The methylation levels of cyp11a1 were increased in ovaries on day 7 and both ovaries and testes on day 14. There were a significant correlation between DNA methylation at specific CpG loci and cyp17a1 and cyp11a1 genes transcription levels. In conclusion, the CpG loci methylation in 5' flanking region appears to involve in the regulation of mRNA expression of cyp17a1 and cyp11a1 mediated by BPA. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Exposure to contaminated sediments induces alterations in the gill epithelia in juvenile Solea senegalensis: a comparative in situ and ex situ study

    Directory of Open Access Journals (Sweden)

    Carla Martins

    2014-06-01

    contaminated sediments. Hypertrophied chloride cells are a consequence of a hindered osmotic regulation by the impairment of ionic active transport, leading to loss-of-function and excessive fluid retention in the cytoplasm. On its turn, a reduction in number and size of gill mucous cells likely reduced the protection provided by mucous to these delicate structures. In general, the alterations were more pronounced in the ex situ study than in situ bioassays, which is probably linked to differences in contaminant bioavailability between laboratory and field scenarios. This variation is likely related to, for instance, estuarine hydrodynamics and sediment steady-state parameters. Interestingly, the results suggest that time of exposure is a key factor, since fewer alterations were observed in animals sampled at the end of the assay (28 days compared to the mid-term (14 days, revealing adaptation to toxicological challenge. In conclusion, mixed sediment contamination can cause physiological alterations in fish gill epithelia that can be determined histologically. These subtle changes may affect the health status of animals by impairing key vital functions such as osmotic balance. As such, physiological alterations to fish gill epithelia may reflect, as in the present case, estuarine sediment contamination even when severe gill lesions are reduced or absent, which mandates caution when interpreting histopathological data in fish for the purpose of environmental risk assessment.

  17. Exposure of Cucurbita pepo to DDE-contamination alters the endophytic community: A cultivation dependent vs a cultivation independent approach.

    Science.gov (United States)

    Eevers, N; Hawthorne, J R; White, J C; Vangronsveld, J; Weyens, N

    2016-02-01

    2,2-bis(p-chlorophenyl)-1,1-dichloro-ethylene (DDE) is the most abundant and persistent degradation product of the pesticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is encountered in contaminated soils worldwide. Both DDE and DDT are classified as Persistent Organic Pollutants (POPs) due to their high hydrophobicity and potential for bioaccumulation and biomagnification in the food chain. Zucchini (Cucurbita pepo ssp. pepo) has been shown to accumulate high concentrations of DDE and other POPs and has been proposed as a phytoremediation tool for contaminated soils. The endophytic bacteria associated with this plant may play an important role in the remedial process. Therefore, this research focuses on changes in endophytic bacterial communities caused by the exposure of C. pepo to DDE. The total bacterial community was investigated using cultivation-independent 454 pyrosequencing, while the cultivable community was identified using cultivation-dependent isolation procedures. For both procedures, increasing numbers of endophytic bacteria, as well as higher diversities of genera were observed when plants were exposed to DDE. Several bacterial genera such as Stenotrophomonas sp. and Sphingomonas sp. showed higher abundance when DDE was present, while, for example Pseudomonas sp. showed a significantly lower abundance in the presence of DDE. These findings suggest tolerance of different bacterial strains to DDE, which might be incorporated in further investigations to optimize phytoremediation with the possible use of DDE-degrading endophytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

    Science.gov (United States)

    Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

    2010-05-01

    The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  19. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    International Nuclear Information System (INIS)

    Herman, D'souza Sunil; Geraldine, Menezes; T, Venkatesh

    2009-01-01

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  20. Tributyltin and triphenyltin exposure promotes in vitro adipogenic differentiation but alters the adipocyte phenotype in rainbow trout.

    Science.gov (United States)

    Lutfi, Esmail; Riera-Heredia, Natàlia; Córdoba, Marlon; Porte, Cinta; Gutiérrez, Joaquim; Capilla, Encarnación; Navarro, Isabel

    2017-07-01

    Numerous environmental pollutants have been identified as potential obesogenic compounds affecting endocrine signaling and lipid homeostasis. Among them, well-known organotins such as tributyltin (TBT) and triphenyltin (TPT), can be found in significant concentrations in aquatic environments. The aim of the present study was to investigate in vitro the effects of TBT and TPT on the development and lipid metabolism of rainbow trout (Onchorynchus mykiss) primary cultured adipocytes. Results showed that TBT and TPT induced lipid accumulation and slightly enhanced peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα) protein expression when compared to a control, both in the presence or absence of lipid mixture. However, the effects were higher when combined with lipid, and in the absence of it, the organotins did not cause complete mature adipocyte morphology. Regarding gene expression analyses, exposure to TBT and TPT caused an increase in fatty acid synthase (fasn) mRNA levels confirming the pro-adipogenic properties of these compounds. In addition, when added together with lipid, TBT and TPT significantly increased cebpa, tumor necrosis factor alpha (tnfa) and ATP-binding cassette transporter 1 (abca1) mRNA levels suggesting a synergistic effect. Overall, our data highlighted that TBT and TPT activate adipocyte differentiation in rainbow trout supporting an obesogenic role for these compounds, although by themselves they are not able to induce complete adipocyte development and maturation suggesting that these adipocytes might not be properly functional. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period.

    Science.gov (United States)

    Philippot, Gaëtan; Gordh, Torsten; Fredriksson, Anders; Viberg, Henrik

    2017-10-01

    Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg -1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The extra mile: Ungulate migration distance alters the use of seasonal range and exposure to anthropogenic risk

    Science.gov (United States)

    Sawyer, Hall; Middleton, Arthur D.; Hayes, Matthew M.; Kauffman, Matthew J.; Monteith, Kevin L.

    2016-01-01

    Partial migration occurs across a variety of taxa and has important ecological and evolutionary consequences. Among ungulates, studies of partially migratory populations have allowed researchers to compare and contrast performance metrics of migrants versus residents and examine how environmental factors influence the relative abundance of each. Such studies tend to characterize animals discretely as either migratory or resident, but we suggest that variable migration distances within migratory herds are an important and overlooked form of population structure, with potential consequences for animal fitness. We examined whether the variation in individual migration distances (20–264 km) within a single wintering population of mule deer (Odocoileus hemionus) was associated with several critical behavioral attributes of migration, including timing of migration, time allocation to seasonal ranges, and exposure to anthropogenic mortality risks. Both the timing of migration and the amount of time animals allocated to seasonal ranges varied with migration distance. Animals migrating long distances (150–250 km) initiated spring migration more than three weeks before than those migrating moderate (50–150 km) or short distances (forage and effectively increase carrying capacity. Clear differences in winter residency, migration duration, and risk of anthropogenic mortality among short-, moderate-, and long-distance migrants suggest fitness trade-offs may exist among migratory segments of the population. Future studies of partial migration may benefit from expanding comparisons of residents and migrants, to consider how variable migration distances of migrants may influence the costs and benefits of migration.

  3. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Herman, D' souza Sunil, E-mail: hermansdsouza@rediffmail.com [Department of Biotechnology, Manipal Life Sciences Centre, KMC, Manipal University, Manipal (India); Geraldine, Menezes, E-mail: gere1@rediffmail.com [Department of Biochemistry and Biophysics, St. John' s Medical College, Koramangala, Bangalore 560034, Karnataka (India); T, Venkatesh, E-mail: venky_tv@hotmail.com [Department of Biochemistry and Biophysics, St. John' s Medical College, Koramangala, Bangalore 560034, Karnataka (India)

    2009-07-30

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  4. Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo.

    Science.gov (United States)

    Törmä, Hans; Lindberg, Magnus; Berne, Berit

    2008-05-01

    Detergents are skin irritants affecting keratinocytes. In this study, healthy volunteers were exposed to water (vehicle) and 1% sodium lauryl sulfate (SLS) under occlusive patch tests for 24 hours. The messenger RNA (mRNA) expression of keratinocyte differentiation markers and of enzymes involved in corneodesmosome degradation was examined in skin biopsies (n=8) during the repair phase (6 hours to 7 days postexposure) using real-time reverse-transcription PCR. It was found that the expression of involucrin was increased at 6 hours, but then rapidly normalized. The expression of transglutaminase 1 exhibited a twofold increase after 24 hours in the SLS-exposed skin. Profilaggrin was decreased after 6 hours. Later (4-7 days), the expression in SLS-exposed areas was >50% above than in control areas. An increased and altered immunofluorescence pattern of involucrin, transglutaminase 1, and filaggrin was also found (n=4). At 6 hours post-SLS exposure, the mRNA expression of kallikrein-7 (KLK-7) and kallikrein-5 (KLK-5) was decreased by 50 and 75%, respectively, as compared with control and water-exposed areas. Thereafter, the expression pattern of KLK-7 and KLK-5 was normalized. Changes in protein expression of KLK-5 were also found. In conclusion, SLS-induced skin barrier defects induce altered mRNA expression of keratinocyte differentiation markers and enzymes degrading corneodesmosomes.

  5. Nitrogen soil emissions and belowground plant processes in Mediterranean annual pastures are altered by ozone exposure and N-inputs

    Science.gov (United States)

    Sánchez-Martín, L.; Bermejo-Bermejo, V.; García-Torres, L.; Alonso, R.; de la Cruz, A.; Calvete-Sogo, H.; Vallejo, A.

    2017-09-01

    Increasing tropospheric ozone (O3) and atmospheric nitrogen (N) deposition alter the structure and composition of pastures. These changes could affect N and C compounds in the soil that in turn can influence soil microbial activity and processes involved in the emission of N oxides, methane (CH4) and carbon dioxide (CO2), but these effects have been scarcely studied. Through an open top chamber (OTC) field experiment, the combined effects of both pollutants on soil gas emissions from an annual experimental Mediterranean community were assessed. Four O3 treatments and three different N input levels were considered. Fluxes of nitric (NO) and nitrous (N2O) oxide, CH4 and CO2 were analysed as well as soil mineral N and dissolved organic carbon. Belowground plant parameters like root biomass and root C and N content were also sampled. Ozone strongly increased soil N2O emissions, doubling the cumulative emission through the growing cycle in the highest O3 treatment, while N-inputs enhanced more slightly NO; CH4 and CO2 where not affected. Both N-gases had a clear seasonality, peaking at the start and at the end of the season when pasture physiological activity is minimal; thus, higher microorganism activity occurred when pasture had a low nutrient demand. The O3-induced peak of N2O under low N availability at the end of the growing season was counterbalanced by the high N inputs. These effects were related to the O3 x N significant interaction found for the root-N content in the grass and the enhanced senescence of the community. Results indicate the importance of the belowground processes, where competition between plants and microorganisms for the available soil N is a key factor, for understanding the ecosystem responses to O3 and N.

  6. Morphological and functional alterations of female reproduction after regular exposure of bamboo shoots of North East India

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    Deotima Sarkar

    2017-01-01

    Full Text Available Objective: To evaluate the effect of daily consumption of bamboo shoots (BS on the morphological features and functional status of the female reproductive system in adult with respect to thyroid.Methods: Adult female rats were divided into control and experimental groups of six each. Control group was given normal diet while experimental group was fed BS by 1/3rd replacement of 180 g of their food i.e. 60 g of BS containing 35 g of goitrogens of cyanogenic origin such that each rat likely consumed 6 mg/100 g of body weight per day for a period of 45 d. Morphological features like changes in body weight and organ weight were noted. Key steroidogenic enzyme levels viz Δ5 3 β hydroxysteroid dehydrogenase (HSD and 17 β HSD along with serum estradiol, estriol and progesterone levels were measured. Estrous cyclicity of the animals monitored regularly followed by histological analysis of thyroid, ovary and uterus at the end of experimentation.Results: Increase in body weight, thyroid gland weight and thyroid stimulating hormone, decrease in serum triiodothyronine and thyroxine, a decrease in ovarian as well as uterine weight and the activity of steroidogenic enzymes Δ5 3 β HSD and β 17 β HSD along with diminished serum estradiol, estriol and progesterone levels were noted; while histological plates showed prominent degenerative changes in both the ovary and uterus. Estrous cyclicity of the treated animals were irregular and almost stopped at diestrous stage of the cycle in the latter stage of the treatment as compared to control.Conclusions: Overall results indicates that BS rich in cyanogenic constituents induces biochemical hypothyroidism in the experimental animals that acts in corroboration to cause morphological and functional alteration of reproductive organs indicating its likely impact in fertility on continued use.

  7. Morphological and functional alterations of female reproduction after regular exposure of bamboo shoots of North East India

    Directory of Open Access Journals (Sweden)

    Deotima Sarkar

    2017-07-01

    Full Text Available Objective: To evaluate the effect of daily consumption of bamboo shoots (BS on the morphological features and functional status of the female reproductive system in adult with respect to thyroid. Methods: Adult female rats were divided into control and experimental groups of six each. Control group was given normal diet while experimental group was fed BS by 1/3rd replacement of 180 g of their food i.e. 60 g of BS containing 35 g of goitrogens of cyanogenic origin such that each rat likely consumed 6 mg/100 g of body weight per day for a period of 45 d. Morphological features like changes in body weight and organ weight were noted. Key steroidogenic enzyme levels viz Δ5 3β hydroxysteroid dehydrogenase (HSD and 17β HSD along with serum estradiol, estriol and progesterone levels were measured. Estrous cyclicity of the animals monitored regularly followed by histological analysis of thyroid, ovary and uterus at the end of experimentation. Results: Increase in body weight, thyroid gland weight and thyroid stimulating hormone, decrease in serum triiodothyronine and thyroxine, a decrease in ovarian as well as uterine weight and the activity of steroidogenic enzymes Δ5 3β HSD and 17β HSD along with diminished serum estradiol, estriol and progesterone levels were noted; while histological plates showed prominent degenerative changes in both the ovary and uterus. Estrous cyclicity of the treated animals were irregular and almost stopped at diestrous stage of the cycle in the latter stage of the treatment as compared to control. Conclusions: Overall results indicates that BS rich in cyanogenic constituents induces biochemical hypothyroidism in the experimental animals that acts in corroboration to cause morphological and functional alteration of reproductive organs indicating its likely impact in fertility on continued use.

  8. Intersex and liver alterations induced by long-term sublethal exposure to 17α-ethinylestradiol in adult male Cnesterodon decemmaculatus (Pisces: Poeciliidae).

    Science.gov (United States)

    Young, Brian Jonathan; López, Gabriela Carina; Cristos, Diego Sebastián; Crespo, Diana Cristina; Somoza, Gustavo Manuel; Carriquiriborde, Pedro

    2017-07-01

    The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC. © 2016 SETAC.

  9. Long-term exposure to xenoestrogens alters some brain monoamines and both serum thyroid hormones and cortisol levels in adult male rats

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    Nashwa M. Saied

    2014-10-01

    Full Text Available The present study was designed to examine the effect of long-term treatment with the phytoestrogen soy isoflavone [(SIF; 43 mg/kg body weight/day] and/or the plastics component bisphenol-A [(BPA; 3 mg/kg body weight/day] on some monoamines in the forebrain and both serum thyroid hormones and cortisol levels of adult rats. Significant increases in serotonin (5-HT and norepinephrine (NE level, and significant decreases in 5-hydroxyindoleacetic acid (5-HIAA level and 5-HIAA/5-HT ratio, were observed after treatment with SIF or BPA. Level of dopamine (DA was increased in SIF-treated group and decreased in BPA-treated group. Activity of monoamine oxidase (MAO was decreased in all treated groups. The level of serum thyroid hormones (fT3 and fT4 was increased after treatment with SIF and decreased after exposure to BPA, while cortisol level was increased in all treated groups. It may be concluded that long-term exposure to SIF or BPA disrupts monoamine levels in the forebrain of adult rats through alteration in the metabolic pathways of amines and disorders of thyroid hormones and cortisol levels.

  10. Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

    Directory of Open Access Journals (Sweden)

    Judy Mumford

    2011-06-01

    Full Text Available Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA. We found that expression of tumor necrosis factor-α (TNF-α, which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-mM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.

  11. Cigarette smoke exposure alters [14C]arachidonic acid metabolism in aortas and platelets of rats fed various levels of selenium and vitamin E

    International Nuclear Information System (INIS)

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1985-01-01

    Rats were placed on a basal diet supplemented with 0, 0.03, or 3 ppm selenium and 0 or 20 ppm vitamin E for 41-43 wk. Selenium deficiency decreased hepatic glutathione peroxidase activity and lowered both aortic prostacyclin (PGI2) and platelet thromboxane (TXA2) production compared to selenium- and vitamin E-supplemented animals. Vitamin E deficiency increased hepatic lipid peroxidation and decreased aortic PGI2 synthesis. Rats exposed daily for 31-32 wk to fresh smoke from a UK 2R1 reference cigarette had carboxyhemoglobin levels of 0.75 +/- 0.12 and 4.73 +/- 0.12% in sham- and smoke-exposed groups, respectively. Animals chronically exposed to cigarette smoke displayed a nearly twofold increase in pulmonary arylhydrocarbon hydroxylase activity. Smoke exposure produced a 26-33% decrease in aortic PGI2 synthesis compared to shams in the Se3E20, Se0.03E20, and Se3E0 groups. Smoking also increased platelet thromboxane 91% and 98% in the Se3E20 and Se3E0 groups compared to shams. It is concluded that cigarette-smoke exposure and selenium or vitamin E deficiency alter aortic PGI2 and platelet TXA2 production

  12. Parental exposure to natural mixtures of POPs reduced embryo production and altered gene transcription in zebrafish embryos.

    Science.gov (United States)

    Lyche, Jan L; Grześ, Irena M; Karlsson, Camilla; Nourizadeh-Lillabadi, Rasoul; Berg, Vidar; Kristoffersen, Anja B; Skåre, Janneche U; Alestrøm, Peter; Ropstad, Erik

    2013-01-15

    Determination of toxicity of complex mixtures has been proposed to be one of the most important challenges for modern toxicology. In this study we performed genome wide transcriptome profiling to assess potential toxicant induced changes in gene regulation in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POPs). The mixtures used were extracted from burbot (Lota lota) liver originating from two lakes (Lake Mjøsa and Lake Losna) belonging to the same freshwater system in Norway. The dominating groups of contaminants were polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane metabolites (DDTs). Because both mixtures used in the present study induced similar effects, it is likely that the same toxicants are involved. The Mjøsa mixture contains high levels of PBDEs while this group of pollutants is low in the Losna mixture. However, both mixtures contain substantial concentrations of PCB and DDT suggesting these contaminants as the predominant contributors to the toxicity observed. The observed effects included phenotypic traits, like embryo production and survival, and gene transcription changes corresponding with disease and biological functions such as cancer, reproductive system disease, cardiovascular disease, lipid and protein metabolism, small molecule biochemistry and cell cycle. The changes in gene transcription included genes regulated by HNF4A, insulin, LH, FSH and NF-κB which are known to be central regulators of endocrine signaling, metabolism, metabolic homeostasis, immune functions, cancer development and reproduction. The results suggest that relative low concentrations of the natural mixtures of POPs used in the present study might pose a threat to wild freshwater fish living in the lakes from which the POPs mixtures originated. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health.

  14. Alteration of carbohydrates metabolism and midgut glucose absorption in Gromphadorhina portentosa after subchronic exposure to imidacloprid and fenitrothion.

    Science.gov (United States)

    Sawczyn, Tomasz; Dolezych, Bogdan; Klosok, Marcin; Augustyniak, Maria; Stygar, Dominika; Buldak, Rafal J; Kukla, Michal; Michalczyk, Katarzyna; Karcz-Socha, Iwona; Zwirska-Korczala, Krystyna

    2012-01-01

    This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.

  15. Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

    Science.gov (United States)

    Pallarés, María Eugenia; Adrover, Ezequiela; Baier, Carlos Javier; Bourguignon, Nadia S; Monteleone, Melisa C; Brocco, Marcela A; González-Calvar, Silvia I; Antonelli, Marta C

    2013-07-01

    Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

  16. Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India.

    Science.gov (United States)

    Balachandar, Vellingiri; Arun, Meyyazhagan; Mohana Devi, Subramaniam; Velmurugan, Palanivel; Manikantan, Pappusamy; Karthick Kumar, Alagamuthu; Sasikala, Keshavarao; Venkatesan, Chinnakulandai

    2010-10-01

    The focal aim of the present study was to identify the genetic alterations occurring in the tannery workers and surrounding inhabitants chronically exposed to hexavalent chromium [Cr(VI)]. A total of 108 samples which includes 72 exposed subjects [36 directly exposed (DE) subjects and 36 indirectly exposed (IE) subjects] and 36 controls were recruited for this study. The exposed subjects and controls were selected based on the Cr level present in air and their urine. Directly exposed subjects were categorized based on their work duration in the tannery industries, whereas the indirectly exposed subjects were categorized based on their year of residence in the place adjacent to tannery industries for more than 3 decades. Controls were normal and healthy. Age was matched for the exposed subjects and controls. The exposed subjects as well as the controls were categorized based on their age (group I, 41 years). Cell cultures were established from blood samples (5 ml from each subject) collected from the subjects (exposed subjects and controls) after obtaining informed consent. G-banding (Giemsa staining) of the cultures, micronucleus (MN) assay and comet assay were used to identify the genetic alterations of individuals exposed to Cr(VI) in comparison with the controls. A higher degree of total CA [12 ± 8.49 (21-25 years)] and MN [18.69 ± 7.39 (11-15 years)] was found in DE subjects compared to other groups. In IE subjects, elevated levels of CA [5.67 ± 1.15 (51-60 years)] and MN [25 ± 9.89 (71-80 years)] were observed. As expected, controls exhibited minimal number of alterations. The overall CA frequency due to Cr exposure was significantly different from that of the controls for both chromatid and chromosome type aberrations (P < 0.05 by ANOVA). The MN/1,000 binucleated cells were significantly increased (P < 0.05) in the peripheral lymphocytes of DE and IE subjects in comparison with controls. The mean tail length of comet assay for DE, IE and controls were

  17. Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGF-R2

    Energy Technology Data Exchange (ETDEWEB)

    Gheorghescu, Anna Kaskova [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Tywoniuk, Bartlomiej [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Duess, Johannes [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); National Children' s Research Centre, Our Lady' s Children' s Hospital, Crumlin, Dublin 12 (Ireland); Buchete, Nicolae-Viorel, E-mail: buchete@ucd.ie [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Thompson, Jennifer, E-mail: jennifer.thompson@ucd.ie [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

    2015-11-15

    Cadmium (Cd) has several industrial applications, and is found in tobacco products, a notable source of human exposure. Vascular endothelial cells are key targets of Cd toxicity. Here, we aim to quantify the alteration to vascular branching pattern following Cd exposure in the chick extra-embryonic membrane (EEM) using fractal analysis, and explore molecular cues to angiogenesis such as VEGF-A and VEGF-R2 expression following Cd treatment. Chicken embryos were incubated for 60 h to Hamburger–Hamilton developmental stage 16–17, then explanted and treated with 50 μL of 50 μmol cadmium acetate (CdAc) or an equivalent volume of equimolar sodium acetate (NaAc). Images of embryos and their area vasculosa (AV) were captured and analyzed at 4 different time points (4, 8, 24 and 48 h) following treatment. Vascular branching in the AV was quantified using its fractal dimension (D{sub f}), estimated using a box counting method. Gallinaceous VEGF ELISA was used to measure the VEGF-A concentration in the EEM following treatment, with determination of the relative expression of VEGF-A and VEGF-R2 using quantitative real-time RT-PCR. Vascular branching increased monotonically in the control group at all time points. The anti-angiogenic effect of Cd exposure on the AV was reflected by a significant reduction in D{sub f} when compared with controls. D{sub f} was more markedly reduced in cultures with abnormal embryos. The expression of VEGF-A protein, and VEGF-A and VEGF-R2 mRNA were reduced in Cd-exposed EEMs. Both molecules contribute to growth, vessel sprouting and branching processes, which supports our findings using fractal analysis. - Highlights: • The chick area vasculosa was undersized in embryos exposed to 50 μM cadmium acetate. • Fractal dimension was reduced in the AV after Cd exposure, indicating decreased branching. • VEGF-A protein was decreased in Cd-treated extraembryonic membranes. • VEGF-A and VEGF-R2 mRNA was decreased in Cd-treated extraembryonic

  18. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    International Nuclear Information System (INIS)

    Dasari, Sameera; Yuan, Yukun

    2009-01-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

  19. Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium.

    Science.gov (United States)

    Foote, A P; Penner, G B; Walpole, M E; Klotz, J L; Brown, K R; Bush, L P; Harmon, D L

    2014-07-01

    Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that

  20. Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Anshu, Kumari; Nair, Ajay Kumar; Kumaresan, U D; Kutty, Bindu M; Srinath, Shoba; Laxmi, T Rao

    2017-12-01

    Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017, 10: 1929-1944. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics

  1. In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

    Science.gov (United States)

    Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

    2015-11-01

    Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    International Nuclear Information System (INIS)

    Grassi, Tony F.; Silva, Glenda N. da; Bidinotto, Lucas T.; Rossi, Bruna F.; Quinalha, Marília M.; Kass, Laura; Muñoz-de-Toro, Mónica; Barbisan, Luís F.

    2016-01-01

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  3. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Tony F. [UNESP – Univ. Estadual Paulista, Botucatu Medical School, Department of Pathology, Botucatu, SP (Brazil); Silva, Glenda N. da [UFOP – Federal University of Ouro Preto, Analysis Clinical Department, Ouro Preto, MG (Brazil); Bidinotto, Lucas T. [Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP (Brazil); Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP (Brazil); Rossi, Bruna F.; Quinalha, Marília M. [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil); Kass, Laura; Muñoz-de-Toro, Mónica [UNL – Universidad Nacional del Litoral, School of Biochemistry and Biological Sciences, Human Pathology Department, Instituto de Salud y Ambiente del Litoral (ISAL, CONICET-UNL), Santa Fe (Argentina); Barbisan, Luís F., E-mail: barbisan@ibb.unesp.br [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil)

    2016-07-15

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  4. Exposure of human JEG-3 cell line to TCDD alters progesterone secretion but does not act on their viability and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Augustowska, K.; Gregoraszczuk, E.L. [Jagiellonian Univ., Krakow (Poland)

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are lipophilic and difficult to metabolize. Any environmental exposure of living organisms to these congeners results in their accumulation in fat tissue and bioconcentration in humans via the food chain. TCDD acts as an endocrine disrupter to alter differentiation and function of the reproductive system. Therefore, these compounds represent a serious health risk, especially to the fetus and infants, whose enzymatic and metabolic systems are not yet mature. Our previous data showed high accumulation of TCDD in cultured human placental tissue which caused a decrease in hormone secretion. However, the mechanism of this action is still unclear. JEG-3 cell line from malignant placental tissue has been used as an in vitro model for investigation of the effects of xenobiotics on placenta toxicity. These cells are morphologically similar to their origin, the trophoblast of the normal first trimester placenta, and produce many peptides and steroid hormones found in normal trophoblast cells, such as hCG, GhRH, progesterone. The aim of the present study was firstly, to show dose- and time-dependent effects of TCDD on progesterone production by JEG-3 cells and secondly, to examine mechanism of its action on cell viability and apoptosis.

  5. Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    Science.gov (United States)

    Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

    2014-02-01

    Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (Pfat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (Pfat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; Pfat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

  6. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

    Directory of Open Access Journals (Sweden)

    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  7. Histopathological alterations and induction of hsp70 in ramshorn snail (Marisa cornuarietis) and zebrafish (Danio rerio) embryos after exposure to PtCl(2).

    Science.gov (United States)

    Osterauer, Raphaela; Köhler, Heinz-R; Triebskorn, Rita

    2010-08-01

    The platinum group metals (PGMs) platinum (Pt), palladium (Pd), and rhodium (Rh) are used in automobile catalytic converters, from which they have been emitted into the environment to an increasing degree during the last 20 years. Despite the bioavailability of these metals to plants and animals, studies determining the effects of PGMs on organisms are extremely rare. In the present study, effects of various concentrations of PtCl(2) (0.1, 1, 10, 50 and 100 microg/L) were investigated with respect to the induction of hsp70 and histopathological alterations in the zebrafish, Danio rerio and the ramshorn snail, Marisa cornuarietis. Histopathological investigations revealed effects of Pt on both species, which varied between slight and strong cellular reactions, depending on the PtCl(2) concentration. The hsp70 level in M. cornuarietis did not show an increase following Pt exposure whereas it was significantly elevated at 100 micorg/L PtCl(2) in D. rerio. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice

    Directory of Open Access Journals (Sweden)

    Xue Luo

    2016-04-01

    Full Text Available Objectives: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs on the immune function of splenic lymphocytes in mice. Material and Methods: Twenty male Kunming mice (6 weeks old, weighing 18– 25 g, were randomly divided into sham exposure (N = 10 and 500 μT MFs (N = 10 groups. The mice in the MFs group were exposed to 500 μT MFs for 8 h daily (5 days/week for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69 in mouse prime splenic lymphocytes activated by para-Methoxyamphetamine (PMA and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640 and exposed to 0 μT, 250 μT, 500 μT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2 at 37°C for 6 h. The levels of interleukin-2 (IL-2, IL-4, interferon-gamma (IFN-γ, GATA binding protein 3 (GATA-3 and T cell-specific T-box transcription factor (T-bet were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR, respectively. The expression of CD69 was checked using the flow cytometry. Results: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. Conclusions: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic

  9. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder.

    Science.gov (United States)

    Kim, Ki Chan; Kim, Pitna; Go, Hyo Sang; Choi, Chang Soon; Park, Jin Hee; Kim, Hee Jin; Jeon, Se Jin; Dela Pena, Ike Campomayor; Han, Seol-Heui; Cheong, Jae Hoon; Ryu, Jong Hoon; Shin, Chan Young

    2013-03-01

    Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results might suggest that the altered glutamatergic neuronal differentiation leads to deranged post-synaptic maturation only in male offspring prenatally exposed to VPA. Consistent with the increased post-synaptic compartment, VPA-exposed male rats showed higher sensitivity to electric shock than VPA-exposed female rats. These results suggest that prenatally VPA-exposed rats show the male preponderance of ASD-like behaviors including defective social interaction similar to human autistic patients, which

  10. Occupational exposure to diesel engine exhaust and alterations in immune/inflammatory markers: a cross-sectional molecular epidemiology study in China.

    Science.gov (United States)

    Bassig, Bryan A; Dai, Yufei; Vermeulen, Roel; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Shiels, Meredith S; Kemp, Troy J; Pinto, Ligia A; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Wong, Jason Y Y; Bin, Ping; Hosgood, H Dean; Hildesheim, Allan; Silverman, Debra T; Rothman, Nathaniel; Zheng, Yuxin; Lan, Qing

    2017-10-26

    The relationship between diesel engine exhaust (DEE), a known lung carcinogen, and immune/inflammatory markers that have been prospectively associated with lung cancer risk is not well understood. To provide insight into these associations, we conducted a cross-sectional molecular epidemiology study of 54 males highly occupationally exposed to DEE and 55 unexposed male controls from representative workplaces in China. We measured plasma levels of 64 immune/inflammatory markers in all subjects using Luminex bead-based assays, and compared our findings to those from a nested case-control study of these markers and lung cancer risk, which had been conducted among never-smoking women in Shanghai using the same multiplex panels. Levels of nine markers that were associated with lung cancer risk in the Shanghai study were altered in DEE-exposed workers in the same direction as the lung cancer associations. Among these, associations with the levels of CRP (β= -0.53; P = 0.01) and CCL15/MIP-1D (β = 0.20; P = 0.02) were observed in workers exposed to DEE and with increasing elemental carbon exposure levels (Ptrends marker positively associated with an increased lung cancer risk, CCL2/MCP-1, were higher among DEE-exposed workers compared with controls in never and former smokers, but not in current smokers (Pinteraction = 0.01). The immunological differences in these markers in DEE-exposed workers are consistent with associations observed for lung cancer risk in a prospective study of Chinese women and may provide some insight into the mechanistic processes by which DEE causes lung cancer. Published by Oxford University Press 2017.

  11. Exposure to bacterial signals does not alter pea aphids' survival upon a second challenge or investment in production of winged offspring.

    Directory of Open Access Journals (Sweden)

    Bas ter Braak

    Full Text Available Pea aphids have an obligate nutritional symbiosis with the bacteria Buchneraaphidicola and frequently also harbor one or more facultative symbionts. Aphids are also susceptible to bacterial pathogen infections, and it has been suggested that aphids have a limited immune response towards such pathogen infections compared to other, more well-studied insects. However, aphids do possess at least some of the genes known to be involved in bacterial immune responses in other insects, and immune-competent hemocytes. One possibility is that immune priming with microbial elicitors could stimulate immune protection against subsequent bacterial infections, as has been observed in several other insect systems. To address this hypothesis we challenged aphids with bacterial immune elicitors twenty-four hours prior to live bacterial pathogen infections and then compared their survival rates to aphids that were not pre-exposed to bacterial signals. Using two aphid genotypes, we found no evidence for immune protection conferred by immune priming during infections with either Serratia marcescens or with Escherichia coli. Immune priming was not altered by the presence of facultative, beneficial symbionts in the aphids. In the absence of inducible immune protection, aphids may allocate energy towards other defense traits, including production of offspring with wings that could escape deteriorating conditions. To test this, we monitored the ratio of winged to unwinged offspring produced by adult mothers of a single clone that had been exposed to bacterial immune elicitors, to live E. coli infections or to no challenge. We found no correlation between immune challenge and winged offspring production, suggesting that this mechanism of defense, which functions upon exposure to fungal pathogens, is not central to aphid responses to bacterial infections.

  12. Proteomic analysis on the alteration of protein expression in the early-stage placental villous tissue of electromagnetic fields associated with cell phone exposure.

    Science.gov (United States)

    Luo, Qiong; Jiang, Ying; Jin, Min; Xu, Jian; Huang, He-Feng

    2013-09-01

    To explore the possible adverse effects and search for cell phone electromagnetic field (EMF)-responsive proteins in human early reproduction, a proteomics approach was employed to investigate the changes in protein expression profile induced by cell phone EMF in human chorionic tissues of early pregnancy in vivo. Volunteer women about 50 days pregnant were exposed to EMF at the average absorption rate of 1.6 to 8.8 W/kg for 1 hour with the irradiation device placed 10 cm away from the umbilicus at the midline of the abdomen. The changes in protein profile were examined using 2-dimensional electrophoresis (2-DE). Up to 15 spots have yielded significant change at least 2- to 2.5-folds up or down compared to sham-exposed group. Twelve proteins were identified- procollagen-proline, eukaryotic translation elongation factor 1 delta, chain D crystal structure of human vitamin D-binding protein, thioredoxin-like 3, capping protein, isocitrate dehydrogenase 3 alpha, calumenin, Catechol-O-methyltransferase protein, proteinase inhibitor 6 (PI-6; SerpinB6) protein, 3,2-trans-enoyl-CoA isomerase protein, chain B human erythrocyte 2,3-bisphosphoglycerate mutase, and nucleoprotein. Cell phone EMF might alter the protein profile of chorionic tissue of early pregnancy, during the most sensitive stage of the embryos. The exposure to EMF may cause adverse effects on cell proliferation and development of nervous system in early embryos. Furthermore, 2-DE coupled with mass spectrometry is a promising approach to elucidate the effects and search for new biomarkers for environmental toxic effects.

  13. Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

    Science.gov (United States)

    Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

    2017-12-01

    Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

  14. Induction of chronic kidney failure in a long-term peritoneal exposure model in the rat: effects on functional and structural peritoneal alterations

    NARCIS (Netherlands)

    Vrtovsnik, François; Coester, Annemieke M.; Lopes-Barreto, Deirisa; de Waart, Dirk R.; van der Wal, Allard C.; Struijk, Dirk G.; Krediet, Raymond T.; Zweers, Machteld M.

    2010-01-01

    A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialysis (PD)

  15. PERINATAL EXPOSURE TO THE PHTHALATES DEHP, BBP AND DINP, BUT NOT DEP, DMP OR DOTP ALTERS SEXUAL DIFFERENTIATION OF THE MALE RAT

    Science.gov (United States)

    In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di (2-bis) ethylhexyl phthalate (DEHP), that inhibit ...

  16. Considering common sources of exposure in association studies - Urinary benzophenone-3 and DEHP metabolites are associated with altered thyroid hormone balance in the NHANES 2007-2008.

    Science.gov (United States)

    Kim, Sujin; Kim, Sunmi; Won, Sungho; Choi, Kyungho

    2017-10-01

    Epidemiological studies have shown that thyroid hormone balances can be disrupted by chemical exposure. However, many association studies have often failed to consider multiple chemicals with possible common sources of exposure, rendering their conclusions less reliable. In the 2007-2008 National Health and Nutrition Examination Survey (NHANES) from the U.S.A., urinary levels of environmental phenols, parabens, and phthalate metabolites as well as serum thyroid hormones were measured in a general U.S. population (≥12years old, n=1829). Employing these data, first, the chemicals or their metabolites associated with thyroid hormone measures were identified. Then, the chemicals/metabolites with possible common exposure sources were included in the analytical model to test the sensitivities of their association with thyroid hormone levels. Benzophenone-3 (BP-3), bisphenol A (BPA), and a metabolite of di(2-ethylhexyl) phthalate (DEHP) were identified as significant determinants of decreased serum thyroid hormones. However, significant positive correlations were detected (p-value<0.05, r=0.23 to 0.45) between these chemicals/metabolites, which suggests that they might share similar exposure sources. In the subsequent sensitivity analysis, which included the chemicals/metabolite with potentially similar exposure sources in the model, we found that urinary BP-3 and DEHP exposure were associated with decreased thyroid hormones among the general population but BPA exposure was not. In association studies, the presence of possible common exposure sources should be considered to circumvent possible false-positive conclusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust.

    Science.gov (United States)

    Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Sehlstedt, Maria; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

    2018-08-14

    Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF 2α , 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats.

    Science.gov (United States)

    Many chemicals released into the environment display estrogenic activity including the oral contraceptive ethinyl estradiol (EE2) and the plastic monomer bisphenol A (BPA). EE2 is present in some aquatic systems at concentrations sufficient to alter reproductive function of fishe...

  19. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    NARCIS (Netherlands)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, T.A.

    2004-01-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris.

  20. Embryonic exposure to an aqueous coal dust extract results in gene expression alterations associated with the development and function of connective tissue and the hematological system, immunological and inflammatory disease, and cancer in zebrafish.

    Science.gov (United States)

    Caballero-Gallardo, Karina; Wirbisky-Hershberger, Sara E; Olivero-Verbel, Jesus; de la Rosa, Jesus; Freeman, Jennifer L

    2018-03-01

    Coal mining is one of the economic activities with the greatest impact on environmental quality. At all stages contaminants are released as particulates such as coal dust. The first aim of this study was to obtain an aqueous coal dust extract and characterize its composition in terms of trace elements by ICP-MS. In addition, the developmental toxicity of the aqueous coal extract was evaluated using zebrafish (Danio rerio) after exposure to different concentrations (0-1000 ppm; μg mL -1 ) to establish acute toxicity, morphology and transcriptome changes. Trace elements within the aqueous coal dust extract present at the highest concentrations (>10 ppb) included Sr, Zn, Ba, As, Cu and Se. In addition, Cd and Pb were found in lower concentrations. No significant difference in mortality was observed (p > 0.05), but a delay in hatching was found at 0.1 and 1000 ppm (p 0.05). Transcriptomic results of zebrafish larvae revealed alterations in 77, 61 and 1376 genes in the 1, 10, and 100 ppm groups, respectively. Gene ontology analysis identified gene alterations associated with the development and function of connective tissue and the hematological system, as well as pathways associated with apoptosis, the cell cycle, transcription, and oxidative stress including the MAPK signaling pathway. In addition, altered genes were associated with cancer; connective tissue, muscular, and skeletal disorders; and immunological and inflammatory diseases. Overall, this is the first study to characterize gene expression alterations in response to developmental exposure to aqueous coal dust residue from coal mining with transcriptome results signifying functions and systems to target in future studies.

  1. In vitro short-term exposure to air pollution PM{sub 2.5-0.3} induced cell cycle alterations and genetic instability in a human lung cell coculture model

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Imane [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Lebanese Atomic Energy Commission – CNRS, Beirut (Lebanon); Verdin, Anthony [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Escande, Fabienne [Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire, Lille (France); Saint-Georges, Françoise [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Cazier, Fabrice [Université de Lille, Lille (France); Centre Commun de Mesures, Université du Littoral-Côte d’Opale, Dunkerque (France); Mulliez, Philippe [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Courcot, Dominique; Shirali, Pirouz [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Gosset, Pierre [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); and others

    2016-05-15

    Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM{sub 2.5-0.3}-exposed coculture model. PM{sub 2.5-0.3} exposure of human AM from the coculture model induced marked cell cycle alterations after 24 h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM{sub 2.5-0.3} was reported in the L132 cells. Exposure of human AM from the coculture model to PM{sub 2.5-0.3} resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM{sub 2.5-0.3} induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability. - Highlights: • Better knowledge on health adverse effects of air pollution PM{sub 2.5}. • Human alveolar macrophage and normal human epithelial lung cell coculture. • Molecular abnormalities from TP53-RB gene signaling pathway. • Loss of heterozygosity and microsatellite instability. • Pathologic changes in morphology and number of cells in relation to airway remodeling.

  2. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

    2017-11-06

    Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

    Science.gov (United States)

    Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

  4. Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli

    Science.gov (United States)

    Bhat, Supriya V.; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E. S.

    2018-01-01

    Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro, and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force – laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage. PMID:29472899

  5. Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease

    Science.gov (United States)

    Acrolein (ACR) is a highly reactive upper airway toxicant that humans are exposed in a variety of environmental situations. Here we examined the effect of ACR exposure on development of immune tolerance in mice. To induce tolerance, female BALB/C mice were intranasally inoculate...

  6. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

    Science.gov (United States)

    Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

  7. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Science.gov (United States)

    Salomäki, Henriikka; Heinäniemi, Merja; Vähätalo, Laura H; Ailanen, Liisa; Eerola, Kim; Ruohonen, Suvi T; Pesonen, Ullamari; Koulu, Markku

    2014-01-01

    Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue. This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  8. Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish.

    Science.gov (United States)

    Glazer, Lilah; Wells, Corinne N; Drastal, Meghan; Odamah, Kathryn-Ann; Galat, Richard E; Behl, Mamta; Levin, Edward D

    2018-05-01

    Polybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints. We included the organophosphate pesticide chlorpyrifos (CPF) due to its well documented neurotoxicity across species from zebrafish to humans. Zebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1, 0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from 5 until 120h post fertilization (hpf). Low exposure levels were determined as those not causing immediate overt toxicity, and behavior assays were conducted in the low-level range. At 144 hpf the larvae were tested for locomotor activity. At approximately 6 months of age adult zebrafish were tested in a behavioral battery including assays for anxiety-related behavior, sensorimotor response and habituation, social interaction, and predator avoidance. In the short-term, larval locomotor activity was reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3μM causing hyperactivity and 1μM or higher causing hypoactivity. In the long-term, adult anxiety-related behavior was reduced in all treatments as measured in both the novel tank dive test and tap test. We show that exposure of zebrafish embryos to low concentrations of the brominated flame retardants BDE-47 and

  9. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    International Nuclear Information System (INIS)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F.; Becquet, Vanessa; Huet, Valérie; Villamil, Luisa; Thomas-Guyon, Hélène; Ahrens, Michael J.; Luna-Acosta, Andrea

    2017-01-01

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  10. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F. [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Becquet, Vanessa; Huet, Valérie [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Villamil, Luisa [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Thomas-Guyon, Hélène [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Ahrens, Michael J., E-mail: michael.ahrens@utadeo.edu.co [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Luna-Acosta, Andrea [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia)

    2017-04-15

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  11. Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): identifying critically vulnerable periods of development.

    Science.gov (United States)

    Hogan, Natacha S; Duarte, Paula; Wade, Michael G; Lean, David R S; Trudeau, Vance L

    2008-05-01

    During the transformation from larval tadpole to juvenile frog, there are critical periods of metamorphic development and sex differentiation that may be particularly sensitive to endocrine disruption. The aim of the present study was to identify sensitive developmental periods for estrogenic endocrine disruption in the northern leopard frog (Rana pipiens) using short, targeted exposures to the synthetic estrogen, ethinylestradiol (EE2). Post-hatch tadpoles (Gosner stage 27) were exposed over five distinct periods of metamorphosis: early (stage 27-30), mid (stage 30-36), early and mid (stage 27-36), late (stage 36-42), and the entire metamorphic period (chronic; stage 27-42). For each period, animals were sampled immediately following the EE2 exposure and at metamorphic climax (stage 42). The effects of EE2 on metamorphic development and sex differentiation were assessed through measures of length, weight, developmental stage, days to metamorphosis, sex ratios and incidence of gonadal intersex. Our results show that tadpoles exposed to EE2 during mid-metamorphosis were developmentally delayed immediately following exposure and took 2 weeks longer to reach metamorphic climax. In the unexposed groups, there was low proportion (0.15) of intersex tadpoles at stage 30 and gonads appeared to be morphologically distinct (male and female) in all individuals by stage 36. Tadpoles exposed early in development displayed a strong female-biased sex ratio compared to the controls. Moreover, these effects were also seen at metamorphic climax, approximately 2-3 months after the exposure period, demonstrating that transient early life-stage exposure to estrogen can induce effects on the reproductive organs that persist into the beginning of adult life-stages.

  12. Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.

    Science.gov (United States)

    Rager, Julia E; Bailey, Kathryn A; Smeester, Lisa; Miller, Sloane K; Parker, Joel S; Laine, Jessica E; Drobná, Zuzana; Currier, Jenna; Douillet, Christelle; Olshan, Andrew F; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

    2014-04-01

    The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. Copyright © 2013 Wiley Periodicals, Inc.

  13. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations

    International Nuclear Information System (INIS)

    Parisot, Florian; Bourdineaud, Jean-Paul; Plaire, Delphine; Adam-Guillermin, Christelle; Alonzo, Frédéric

    2015-01-01

    Highlights: • We exposed three successive generations of Daphnia magna to chronic gamma radiation. • We examined DNA alterations and effects on survival, growth and reproduction. • DNA alterations were accumulated over a generation and transmitted to the progeny. • Effects on survival and reproduction, and delay in growth increased over generations. - Abstract: This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h −1 ). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h −1 increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h −1 in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h −1 in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h −1 in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h −1 in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h −1 at hatching to 0.007 mGy h −1 after ∼21 days) and from F0 to F2 (0.070 mGy h −1 at hatching to 0.007 mGy h −1 after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h −1 and DNA alterations significant at highest dose rates only. The study improved our understanding of

  14. Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Mi-Hee; Pflugmacher, Stephan, E-mail: stephan.pflugmacher@tu-berlin.de

    2013-08-15

    Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H{sub 2}O{sub 2}, which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

  15. Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

    International Nuclear Information System (INIS)

    Ha, Mi-Hee; Pflugmacher, Stephan

    2013-01-01

    Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H 2 O 2 , which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

  16. 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

    International Nuclear Information System (INIS)

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L.

    2007-01-01

    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

  17. Does Cancer Start in the Womb? Altered Mammary Gland Development and Predisposition to Breast Cancer due to in Utero Exposure to Endocrine Disruptors

    OpenAIRE

    Soto, Ana M.; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-01-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary ...

  18. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Directory of Open Access Journals (Sweden)

    Henriikka Salomäki

    Full Text Available AIMS: Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. MATERIALS AND METHODS: Female mice were on a high fat diet (HFD prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD and subjected to HFD at adulthood (10-11 weeks. Body weight and several metabolic parameters (e.g. body composition and glucose tolerance were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. RESULTS: Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC was prominently affected both in the neonatal liver and adipose tissue. CONCLUSION: This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  19. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

    OpenAIRE

    Buckley, Jill; Willingham, Emily; Agras, Koray; Baskin, Laurence S

    2006-01-01

    Abstract Background Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at ...

  20. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

    Science.gov (United States)

    Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

    2017-07-01

    The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

    Science.gov (United States)

    Cromer, W. E.; Zawieja, D. C.

    2018-05-01

    Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

  2. Chronic ozone exposure alters the secondary metabolite profile, antioxidant potential, anti-inflammatory property, and quality of red pepper fruit from Capsicum baccatum.

    Science.gov (United States)

    Bortolin, Rafael Calixto; Caregnato, Fernanda Freitas; Divan Junior, Armando Molina; Zanotto-Filho, Alfeu; Moresco, Karla Suzana; Rios, Alessandro de Oliveira; Salvi, Aguisson de Oliveira; Ortmann, Caroline Flach; de Carvalho, Pâmela; Reginatto, Flávio Henrique; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-07-01

    Tropospheric ozone (O3) background concentrations have increased since pre-industrial times, reaching phytotoxic concentrations in many regions globally. However, the effect of high O3 concentrations on quality of fruit and vegetables remains unknown. Here, we evaluated whether O3 pollution alters the quality of Capsicum baccatum peppers by changing the secondary compound profiles and biological activity of the fruit. C. baccatum pepper plants were exposed to ozone for 62 days in an open-top chamber at a mean O3 concentration of 171.6µg/m(3). Capsaicin levels decreased by 50% in the pericarp, but remained unchanged in the seeds. In contrast, the total carotenoid content increased by 52.8% in the pericarp. The content of total phenolic compounds increased by 17% in the pericarp. The total antioxidant potential decreased by 87% in seeds of O3-treated plants. The seeds contributed more than the pericarp to the total radical-trapping antioxidant potential and total antioxidant reactivity. O3 treatment impaired the ferric-reducing antioxidant power of the seeds and reduced NO(•)-scavenging activity in the pericarp. However, O3 treatment increased ferrous ion-chelating activity and hydroxyl radical-scavenging activity in the pericarp. Our results confirm that O3 alters the secondary metabolite profile of C. baccatum pepper fruits and, consequently, their biological activity profile. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking

    Directory of Open Access Journals (Sweden)

    Matturri Luigi

    2010-07-01

    Full Text Available Abstract Background The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma and thoracic spinal cord (central canal ependyma of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking. Results Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy. Conclusions We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

  4. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations

    Energy Technology Data Exchange (ETDEWEB)

    Parisot, Florian [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France); Bourdineaud, Jean-Paul [UMR 5805 EPOC – OASU, Station marine d’Arcachon, Université Bordeaux 1, Arcachon 33120 (France); Plaire, Delphine; Adam-Guillermin, Christelle [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France); Alonzo, Frédéric, E-mail: frederic.alonzo@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France)

    2015-06-15

    Highlights: • We exposed three successive generations of Daphnia magna to chronic gamma radiation. • We examined DNA alterations and effects on survival, growth and reproduction. • DNA alterations were accumulated over a generation and transmitted to the progeny. • Effects on survival and reproduction, and delay in growth increased over generations. - Abstract: This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h{sup −1}). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h{sup −1} increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h{sup −1} in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h{sup −1} in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h{sup −1} in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h{sup −1} in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h{sup −1} at hatching to 0.007 mGy h{sup −1} after ∼21 days) and from F0 to F2 (0.070 mGy h{sup −1} at hatching to 0.007 mGy h{sup −1} after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h{sup −1} and DNA alterations significant at highest

  5. Alteration of cytochrome P450 1 regulation and HSP 70 level in brain of juvenile common carp (Cyprinus carpio) after chronic exposure to tributyltin.

    Science.gov (United States)

    Li, Zhi-Hua; Zhong, Li-Qiao; Wu, Yan-Hua; Mu, Wei-Na

    2016-02-01

    Tributyltin (TBT), a toxic contaminant in aquatic environments, has bio-accumulated in aquatic food webs throughout the world and can be found at toxic levels in some biota. However, the molecular mechanisms and effects of TBT are not fully understood. The aim of the present study was to investigate the effect of long-term exposure of TBT on cytochrome P450 (CYP450) 1 regulation and heat-shock proteins (HSPs) profiling in brain of freshwater teleost. The effects of long-term exposure to TBT on mRNA expression of cytochrome P450 (CYP450) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in the brain of common carp were evaluated, as well as HSP 70 level. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on EROD activity, HSP 70 level and CYP450 1 family genes expression). The mRNA expression of CYP450 1 family genes (CYP1A, CYP1B, CYP1C1 and CYP1C2) suggested that CYP1A was to accommodate most EROD activity in fish, but other CYP450 forms also involved in this proceeding. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity and could be used as potential biomarkers for monitoring the TBT pollution in the field.

  6. Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

    Science.gov (United States)

    Maskey, Dhiraj; Kim, Hyung Gun; Suh, Myung-Whan; Roh, Gu Seob; Kim, Myeung Ju

    2014-08-01

    The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region

  7. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

    Science.gov (United States)

    Ebrahimzadeh Bideskan, Alireza; Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Hosseini, Mahmoud; Rajabzadeh, Aliakbar

    2017-07-05

    The usage of Titanium dioxide nanoparticles (TiO 2 -NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO 2 -NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO 2 -NPs on rat offspring hippocampus during developmental period. Pregnant and lactating Wistar rats received intragastric TiO 2 -NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO 2 -NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO 2 -NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO 2 -NPs group significantly increased and decreased, respectively (P<0.01). These findings provide strong evidence that maternal exposure to TiO 2 -NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and

  8. Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

    Science.gov (United States)

    Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

    2015-01-01

    Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

  9. RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

    2017-07-01

    Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Early post-natal exposure to intermittent hypoxia in rodents is pro-inflammatory, impairs white matter integrity and alters brain metabolism

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L.; Hunt, Carl E.

    2017-01-01

    Background Preterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury. Methods Rat pups were exposed to IH from P2–P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20–P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed. Results Pups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr and Gly/Cr and increases in TCho and GPC in the brainstem and decreases in NAA/Cho in the hippocampus. Conclusions We conclude that early postnatal exposure to IH, similar in magnitude experienced in human preterm infants, is associated with evidence for pro-inflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia. PMID:28388601

  12. Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.

    Science.gov (United States)

    Oh, Jung-Hwa; Son, Mi-Young; Choi, Mi-Sun; Kim, Soojin; Choi, A-Young; Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Janghwan; Song, Chang Woo; Yoon, Seokjoo

    2016-05-15

    Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring

    Science.gov (United States)

    Clayton, Zoe E.; Vickers, Mark H.; Bernal, Angelica; Yap, Cassandra; Sloboda, Deborah M.

    2015-01-01

    Aim Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation. Methods Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR. Results Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes. Conclusions Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may

  14. In Vitro Exposure of Porcine Ovarian Follicular Cells to PCB 153 Alters Steroid Secretion But Not Their Viability—Preliminary Study

    Directory of Open Access Journals (Sweden)

    Ewa L. Gregoraszczuk

    2002-01-01

    Full Text Available In our previous paper[1], we demonstrated that porcine follicles collected during the early stage of development are the most sensitive to the toxic action of polychlorinated biphenyl 153 (PCB 153. Follicles of this type were collected to test the effect of PCB 153 on cell steroidogenesis and viability. Cocultures of granulosa and theca cells were grown in M199 medium at 37ºC. Control cultures were maintained in that medium alone, while experimental ones were supplemented with PCB 153 at doses of 5, 10, 50, and 100 ng/ml. After 48, 96, and 144 h, media were collected for steroid analysis and cell viability was measured using an LDH (lactate dehydrogenase activity cytotoxicity test. A 2-day exposure of follicular cells to all the investigated doses of PCB 153 caused a statistically significant decrease in progesterone (P4 secretion, while in doses of 50 and 100 ng/ml there was also a decrease in testosterone (T secretion. No effect on estradiol (E2 secretion was observed. The observed decrease in P4 and T secretion, and lack of any statistically significant effect on E2 secretion by cells from small follicles exposed for 48 h to PCB, suggests that PCB 153 acts before P4 formation. Longer exposures caused an increase in P4 secretion, with a concomitant drastic decrease in T secretion and a tendency to decrease the E2 secretion, suggesting inhibition of P450 17α hydroxysteroid dehydrogenase, an enzyme that converts P4 to T. The observed PCB 153–induced increase in P4 secretion by cells collected from small antral follicles, with a concomitant decrease in E2 secretion, accounts for the induction of luteinization and, in this case, inhibition of aromatization process in the follicles. However, in all doses tested and at all times of exposure, PCB 153 had no effect on cell viability. These findings suggest different time of exposure–dependent action of PCB 153 on particular steps of steroidogenesis but not action on cell viability. These results

  15. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice.

    Science.gov (United States)

    Buckley, Jill; Willingham, Emily; Agras, Koray; Baskin, Laurence S

    2006-02-21

    Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors alpha and beta, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen alpha and beta, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor alpha mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor alpha and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. The results suggest that

  16. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

    Directory of Open Access Journals (Sweden)

    Baskin Laurence S

    2006-02-01

    Full Text Available Abstract Background Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. Methods We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors α and β, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females, we measured the lengths of the casts and performed ANOVA analysis on these data. Results Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias and masculinizing females (longer urethras. Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen α and β, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor α mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor α and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl

  17. Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles

    International Nuclear Information System (INIS)

    Oh, Jung-Hwa; Son, Mi-Young; Choi, Mi-Sun; Kim, Soojin; Choi, A-young; Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Janghwan; Song, Chang Woo; Yoon, Seokjoo

    2016-01-01

    Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10–200 μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24 h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24 h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. - Highlights: • This system served as a suitable model for developmental neurotoxicity testing. • Ag NPs induce the apoptosis in human neural cells by ROS generation. • Genes for development of neurons were dysregulated in response to Ag NPs. • Molecular events during early developmental neurotoxicity were proposed.

  18. Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

    Science.gov (United States)

    Colbert, Nathan K.W.; Pelletier, Nicole C.; Cote, Joyce M.; Concannon, John B.; Jurdak, Nicole A.; Minott, Sara B.; Markowski, Vincent P.

    2005-01-01

    In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs. PMID:15929892

  19. Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung-Hwa [Korea Institute of Toxicology (KIT), Daejeon 34114 (Korea, Republic of); Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113 (Korea, Republic of); Son, Mi-Young [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahangno, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of functional genomics, University of Science & Technology, 217 Gajungro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Choi, Mi-Sun; Kim, Soojin; Choi, A-young [Korea Institute of Toxicology (KIT), Daejeon 34114 (Korea, Republic of); Lee, Hyang-Ae; Kim, Ki-Suk [Korea Institute of Toxicology (KIT), Daejeon 34114 (Korea, Republic of); Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113 (Korea, Republic of); Kim, Janghwan [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahangno, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of functional genomics, University of Science & Technology, 217 Gajungro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Song, Chang Woo, E-mail: cwsong@kitox.re.kr [Korea Institute of Toxicology (KIT), Daejeon 34114 (Korea, Republic of); Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113 (Korea, Republic of); Yoon, Seokjoo, E-mail: sjyoon@kitox.re.kr [Korea Institute of Toxicology (KIT), Daejeon 34114 (Korea, Republic of); Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113 (Korea, Republic of)

    2016-05-15

    Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10–200 μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24 h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24 h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. - Highlights: • This system served as a suitable model for developmental neurotoxicity testing. • Ag NPs induce the apoptosis in human neural cells by ROS generation. • Genes for development of neurons were dysregulated in response to Ag NPs. • Molecular events during early developmental neurotoxicity were proposed.

  20. Structural alterations in embryos and alevins of the Atlantic salmon, Salmo salar 1. , induced by continuous or short-term exposure to acidic levels of pH

    Energy Technology Data Exchange (ETDEWEB)

    Daye, P.G.; Garside, E.T.

    1980-01-01

    Embryos of the Atlantic Salmon, salmo salar l., were incubated continuously from fertilization, at pH 6.8 (control), 5.0, 4.5, 4.3, 4.0, and 3.7, at 5-6 degrees C. The subsequent alvins in these environments were maintained at these levels for 40 days after hatching. Generally, lethal and sublethal injuries were separable only as to degree and distribution. Sublethal alterations occurred in the integument, gill blood, and blood vascular structures of all live alevins incubated at pH 5.0 and lower. At pH 4.5 and lower, injuries also occurred in brain, optic retina, kidney, and spleen. Some tissue regeneration occurred in the embryonal rudimentary integument at pH 4.5 and lower. Regeneration also occurred but to a lesser degree in pseudobranch, kidney, spleen, and erythrocytes. Injury of the integument was the apparent cause of death in prehatching embryos since it is the major site of respiration and ion exchange. As gills expand in posthatching alevins, they assume these functions and destruction of branchial epithelium then becomes the prime cause of death. The nature of cell injury and consequent dysgenesis at tissue and organ levels are not ascribable uniquely to acidic stress. Some injuries are similar to those caused variously by heavy metals, detergents, halogenated organic compounds, some petroleum fractions, and chronic and acute high temperature in postalevin stages of several species of fish.

  1. Exposure to predicted precipitation patterns decreases population size and alters community structure of cyanobacteria in biological soil crusts from the Chihuahuan Desert.

    Science.gov (United States)

    Fernandes, Vanessa M C; Machado de Lima, Náthali Maria; Roush, Daniel; Rudgers, Jennifer; Collins, Scott L; Garcia-Pichel, Ferran

    2018-01-01

    Cyanobacteria typically colonize the surface of arid soils, building biological soil crust (biocrusts) that provide a variety of ecosystem benefits, ranging from fertilization to stabilization against erosion. We investigated how future scenarios in precipitation anticipated for the Northern Chihuahuan Desert affected abundance and composition of biocrust cyanobacteria in two grassland ecosystems. Scenarios included a decrease in precipitation and a delay of monsoon rainfall. After three years, both treatments negatively affected cyanobacteria, although the effects of monsoon delay were milder than those of decreased precipitation. Mature biocrusts in black grama grassland suffered severe losses in cyanobacterial biomass and diversity, but compositionally simpler biocrusts in blue grama-dominated grassland maintained biomass, only suffering diversity losses. This could be partially explained by the differential sensitivity of cyanobacterial taxa: nitrogen-fixing Scytonema spp. were the most sensitive, followed by phylotypes in the Microcoleus steenstrupii complex. Microcoleus vaginatus was the least affected in all cases, but is known to be very sensitive to warming. We predict that altered precipitation will tend to prevent biocrusts from reaching successional maturity, selecting for M. vaginatus over competing M. steenstrupii, among pioneer biocrust-formers. A shift towards heat-sensitive M. vaginatus could ultimately destabilize biocrusts when precipitation changes are combined with global warming. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.

    Directory of Open Access Journals (Sweden)

    Eric J Chater-Diehl

    Full Text Available The molecular basis of Fetal Alcohol Spectrum Disorders (FASD is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse's lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as "Free radical scavenging". We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was "Peroxisome biogenesis"; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.

  3. Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

    Science.gov (United States)

    Marks, Wendie; Fournier, Neil M; Kalynchuk, Lisa E

    2009-08-04

    We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depression-like behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.

  4. Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.

    Science.gov (United States)

    Chater-Diehl, Eric J; Laufer, Benjamin I; Castellani, Christina A; Alberry, Bonnie L; Singh, Shiva M

    2016-01-01

    The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse's lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as "Free radical scavenging". We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was "Peroxisome biogenesis"; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.

  5. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers.

    Science.gov (United States)

    Tonneijck, A E G; Franzaring, J; Brouwer, G; Metselaar, K; Dueck, Th A

    2004-09-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l(-1) ozone (CF+25), non-filtered air (NF), non-filtered air plus 25 nl l(-1) ozone (NF+25) and non-filtered air plus 50 nl l(-1) ozone (NF+50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species.

  6. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    Energy Technology Data Exchange (ETDEWEB)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, Th.A

    2004-09-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l{sup -1} ozone (CF + 25), non-filtered air (NF), non-filtered air plus 25 nl l{sup -1} ozone (NF + 25) and non-filtered air plus 50 nl l{sup -1} ozone (NF + 50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species.

  7. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    International Nuclear Information System (INIS)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, Th.A.

    2004-01-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l -1 ozone (CF + 25), non-filtered air (NF), non-filtered air plus 25 nl l -1 ozone (NF + 25) and non-filtered air plus 50 nl l -1 ozone (NF + 50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species

  8. A single exposure to cocaine during development elicits regionally-selective changes in basal basic Fibroblast Growth Factor (FGF-2) gene expression and alters the trophic response to a second injection.

    Science.gov (United States)

    Giannotti, Giuseppe; Caffino, Lucia; Malpighi, Chiara; Melfi, Simona; Racagni, Giorgio; Fumagalli, Fabio

    2015-02-01

    During adolescence, the brain is maturing and more sensitive to drugs of abuse that can influence its developmental trajectory. Recently, attention has been focused on basic fibroblast growth factor (FGF-2) given that its administration early in life enhances the acquisition of cocaine self-administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)). Additionally, we found that abstinence from adolescent cocaine exposure long lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology (Berl) 225:553-60, 2013 ). The objectives of the study are to evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35 alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days later. We found regional differences in the FGF-2 expression pattern as either the first or the second injection of cocaine by themselves upregulated FGF-2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating it in the hippocampus. The first injection influences the trophic response of the second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2 changes produced by cocaine in saline-pretreated rats were prevented in cocaine-pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7 days after the first injection, the cocaine-induced FGF-2 changes were modified by the subsequent exposure to the psychostimulant. These findings show that a single cocaine injection is sufficient to produce enduring changes in the adolescent brain and indicate that early cocaine priming alters the mechanisms regulating the trophic response in a brain region-specific fashion.

  9. Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke

    Directory of Open Access Journals (Sweden)

    Jon M. Florence

    2018-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression of this disease remains unknown. Our laboratory has demonstrated that Bruton’s tyrosine kinase (Btk is a critical regulator of pro-inflammatory processes in the lungs and that Btk controls expression of matrix metalloproteinase-9 (MMP-9 in the alveolar compartment. For this study apolipoprotein E null (ApoE−/− mice were exposed to SHS to facilitate study in a COPD/atherosclerosis comorbidity model. We applied two types of treatments, animals received either a pharmacological inhibitor of Btk or MMP-9 specific siRNA to minimize MMP-9 expression in endothelial cells or neutrophils. We have shown that these treatments had a protective effect in the lung. We have noted a decrease in alveolar changes related to SHS induced inflammation in treated animals. In summary, we are presenting a novel concept in the field of COPD, i.e., that Btk may be a new drug target for this disease. Moreover, cell specific targeting of MMP-9 may also benefit patients affected by this disease.

  10. Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

    Directory of Open Access Journals (Sweden)

    Rongli Sun

    2016-10-01

    Full Text Available Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC, red blood cell (RBC, platelet (Pit counts, and hemoglobin (Hgb concentration. Investigation of the effects of benzene on the expression of FA transport- and β-oxidation-related enzymes showed that expression of proteins Cpt1a, Crat, Acaa2, Aldh1l2, Acadvl, Crot, Echs1, and Hadha was significantly increased. The ATP levels and mitochondrial membrane potential decreased in mice exposed to benzene. Meanwhile, reactive oxygen species (ROS, hydrogen peroxide (H2O2, and malondialdehyde (MDA levels were significantly increased in the benzene group. Our results indicate that benzene induces increased expression of FA transport and β-oxidation enzymes, mitochondrial dysfunction, and oxidative stress, which may play a role in benzene-induced hematotoxicity.

  11. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Solt, Anna C; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Nuse, Bryan; Herritt, Lou; Villarreal-Calderón, Rafael; Osnaya, Norma; Stone, Ida; García, Raquel; Brooks, Diane M; González-Maciel, Angelica; Reynoso-Robles, Rafael; Delgado-Chávez, Ricardo; Reed, William

    2008-02-01

    Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

  12. Long-term exposure to slightly elevated air temperature alleviates the negative impacts of short term waterlogging stress by altering nitrogen metabolism in cotton leaves.

    Science.gov (United States)

    Wang, Haimiao; Chen, Yinglong; Xu, Bingjie; Hu, Wei; Snider, John L; Meng, Yali; Chen, Binglin; Wang, Youhua; Zhao, Wenqing; Wang, Shanshan; Zhou, Zhiguo

    2018-02-01

    Short-term waterlogging and chronic elevated temperature occur frequently in the Yangtze River Valley, yet the effects of these co-occurring environments on nitrogen metabolism of the subtending leaf (a major source leaf for boll development) have received little attention. In this study, plants were exposed to two temperature regimes (31.6/26.5 °C and 34.1/29.0 °C) and waterlogging events (0 d, 3 d, 6 d) during flowering and boll development. The results showed that the effects of waterlogging stress and elevated temperature in isolation on nitrogen metabolism were quite different. Waterlogging stress not only limited NR (EC 1.6.6.1) and GS (EC 6.3.1.2) activities through the down-regulation of GhNR and GhGS expression for amino acid synthesis, but also promoted protein degradation by enhanced protease activity and peptidase activity, leading to lower organ and total biomass (reduced by 12.01%-27.63%), whereas elevated temperature inhibited protein degradation by limited protease activity and peptidase activity, promoting plant biomass accumulation. Furthermore, 2-3 °C chronic elevated temperature alleviated the negative impacts of a brief (3 d) waterlogging stress on cotton leaves, with the expression of GhNiR up-regulated, the activities of NR, GS and GOGAT (EC 1.4.7.1) increased and the activities of protease and peptidase decreased, leading to higher protein concentration and enhanced leaf biomass for EW 3 relative to AW 3 . The results of the study suggested that exposure to slightly elevated air temperature improves the cotton plants' ability to recover from short-term (3 d) waterlogging stress by sustaining processes associated with nitrogen assimilation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD in Han/Wistar and Long–Evans rats with different aryl hydrocarbon receptor (AhR structures

    Directory of Open Access Journals (Sweden)

    Sabrina B. Sholts

    2015-01-01

    Full Text Available Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W and dioxin-sensitive Long–Evans (L–E rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM and dose–response modeling. The strongest effects were shown by L–E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs for cranial size reduction in L–E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L–E rats, respectively, most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L–E rats had vaults and bases of comparable size, the face was 6.4% larger in L–E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on

  14. A Study of the Modulating Action of Quercetin on Biochemical and Histological Alterations Induced by Lead Exposure in the Liver and Kidney of Rats.

    Science.gov (United States)

    Mohammed, Ghena M.; Sedky, Azza; Elsawy, Hany

    2017-06-30

    Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i.p. quercetin (50 mg/kg b.w.); (iv) lead and quercetin group received i.p. lead acetate (20 mg/kg b.w.) followed by i.p. quercetin (50 mg/kg b.w.) for 4 weeks. The lead concentrations were determined in the liver and kidney tissues. Liver marker enzymes, bilirubin, albumin, total protein, creatinine, uric acid and urea, were assessed in the serum and light microscopic studies were performed. The results showed that lead acetate administration was associated with an increase in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, total bilirubin, creatinine, uric acid, urea levels. Lead accumulation in kidneys and liver tissues was also found, but were associated with decrease in albumin and total protein in comparison with the respective mean values of the control. Lead acetate caused numerous histological alterations in the liver, including chronic inflammation, bilary hyperplasia, edema, congestion, Kupffer cells hyperplasia and hemosiderosis, and in the kidney, including tubular dilation, atrophy of glomerular tuft, widening of urinary space and mild fibroblast. In contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values and improved structure of liver and kidney with significant decreases in the severity of histopathological changes when compared with the lead acetate group. In conclusion, treatment with quercetin may provide a

  15. Exposure to di(n-butyl)phthalate and benzo(a)pyrene alters IL-1β secretion and subset expression of testicular macrophages, resulting in decreased testosterone production in rats

    International Nuclear Information System (INIS)

    Zheng Shanjun; Tian Huaijun; Cao Jia; Gao Yuqi

    2010-01-01

    Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1β), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1β secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plus BaP (DBP + BaP: 50 + 1 or 250 + 5 mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250 mg/kg/day; BaP: 1 or 5 mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90 days, the relative expression of macrophage subsets and their functions changed. ED2 + testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1β secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1β secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1β, resulted in enhanced production of IL-1β as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis.

  16. Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

    Science.gov (United States)

    Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

    2015-01-01

    In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that

  17. Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

    Directory of Open Access Journals (Sweden)

    Muneko Nishijo

    Full Text Available In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1 a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2 a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3 a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4 a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits

  18. Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    Science.gov (United States)

    Markowski, V P; Zareba, G; Stern, S; Cox, C; Weiss, B

    2001-06-01

    Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

  19. Exposição ao ruído ocupacional: alterações no exame de emissões otoacústicas Exposure to occupational noise: otoacoustic emissions test alterations

    Directory of Open Access Journals (Sweden)

    Frederico Prudente Marques

    2006-06-01

    Full Text Available A exposição ao ruído ocupacional pode provocar lesões em nível da orelha interna, sendo que o registro das Emissões Otoacústicas por Produtos de Distorção (EOAPD é capaz de identificar alterações auditivas iniciais relacionadas a tais lesões, auxiliando no diagnóstico precoce da PAIRO. OBJETIVO: Avaliar as EOAPD como método de diagnóstico de alterações fisiopatológicas iniciais provocadas por exposição ao ruído ocupacional. FORMA DE ESTUDO: Transversal. MÉTODO: Foram avaliados 74 trabalhadores do sexo masculino, lotados no Campus Universitário da Universidade de São Paulo na capital, divididos em dois grupos pareados por idade e com exame de audiometria tonal dentro de limites aceitáveis: 37 indivíduos expostos ao ruído ocupacional e 37 não-expostos. RESULTADOS: A estimativa do risco (Odds Ratio de ausência de resposta no registro das EOAPD foi 12 vezes maior para o grupo de expostos ao ruído ocupacional (IC 95% 3,1 - 45,9, nas freqüências de 3, 4 e 6 kHz agrupadas. CONCLUSÃO: Os resultados sugerem que a exposição ao ruído ocupacional pode provocar alterações nos registros das EOAPD, mesmo em indivíduos com exame de audiometria tonal dentro de limites aceitáveis, indicando que este exame pode ser importante como método de diagnóstico precoce da PAIRO.Exposure to occupational noise may cause injuries to the inner ear, and the distortion product otoacoustic emissions (DPOAE may identify initial auditory alterations, thus assisting NIHL early diagnosis. AIM: The goal of this study was to evaluate DPOAE as a method to diagnose early physiopathological alterations caused by occupational noise exposure. STUDY DESIGN: Transversal. METHODS: 74 workers of the University of São Paulo, in the capital city of the State, participated in this investigation. They were divided in two age-matched groups and with tonal audiometric values within the acceptable limits: 37 were exposed to occupational noise and 37 were not

  20. Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

    Science.gov (United States)

    Maldonado-Devincci, Antoniette M; Cook, Jason B; O'Buckley, Todd K; Morrow, Danielle H; McKinley, Raechel E; Lopez, Marcelo F; Becker, Howard C; Morrow, A Leslie

    2014-10-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%). These data

  1. Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kakinuma, Shizuko, E-mail: skakinum@nirs.go.jp [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Doi, Kazutaka; Yoshinaga, Shinji [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Yoshiya [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-09-01

    Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

  2. Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep.

    Science.gov (United States)

    Gallaher, B W; Breier, B H; Keven, C L; Harding, J E; Gluckman, P D

    1998-12-01

    It has been demonstrated in several animal models that undernutrition in utero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of periconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after conception, and then both groups were allowed to feed ad libitum. These groups were further divided at day 105 of gestation, either being fed ad libitum or undernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the development of a specific homologous RIA to measure ovine IGF-binding protein-3 (IGFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (Pfetal plasma IGFBP-2 levels were unchanged. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 105 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (Pfetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. These results suggest that exposure to maternal periconceptual undernutrition reprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, altering its response to undernutrition in late gestation.

  3. Environmental exposure and altered menstrual function

    Energy Technology Data Exchange (ETDEWEB)

    Keye, W.R. Jr.

    1984-01-01

    The impact of environmental agents and occupational factors on hypothalamic and pituitary function and menstruation are poorly understood. To date, most research related to environment, occupation, and reproduction has focused on pregnancy outcome, not menstrual function. It is imperative, however, that menstrual function be considered as an outcome variable in the study of reproduction and occupation.

  4. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  5. Cytologic alterations in the oral mucosa after chronic exposure to ethanol Alterações citológicas na mucosa bucal após exposição crônica ao etanol

    Directory of Open Access Journals (Sweden)

    Sílvia Regina de Almeida Reis

    2006-04-01

    Full Text Available The effects of ethanol alone on the oral mucosa are still poorly understood, especially because there are few non-smoking chronic consumers of alcoholic beverages. The aim of this study was to evaluate the frequency of micronucleus, abnormal nucleus/cytoplasm ratio, pyknosis, karyorrhexis and karyolysis in exfoliated cells from the buccal mucosa and from the lateral border of the tongue in 36 non-smoker alcoholics (ethanol group and 18 non-smokers and non-drinkers (control group. The Papanicolaou method was used. Since alcoholics generally have hepatobiliary involvement, the association between serum gamma-glutamyl transpeptidase (GGT and some of the analyzed oral mucosa alterations was also investigated. The ethanol group showed a significant increase in the frequency of all alterations analyzed in the tongue cells when compared with the control group (p 0.05; Mann-Whitney. In the ethanol group, the correlation between serum GGT and the frequency of micronucleus and abnormal nucleus/cytoplasm ratio in oral mucosa cells was not significant (p > 0.05; Spearman. In conclusion, chronic exposure to ethanol may be associated with carcinogenic cytologic changes in the oral mucosa, even in the absence of tobacco smoking. These alterations were not correlated with hepatobiliary injury.Os efeitos do etanol isoladamente sobre a mucosa bucal permanecem pouco esclarecidos, sobretudo devido ao baixo número de não-fumantes consumidores crônicos de bebidas alcoólicas. O objetivo deste estudo foi avaliar as freqüências de micronúcleo, relação núcleo/citoplasma anormal, picnose, cariorrexe e cariólise em células esfoliadas da mucosa jugal e do bordo lateral da língua de 36 alcoólatras não-fumantes (grupo etanol e 18 abstêmios de álcool e fumo (grupo controle. O método de Papanicolaou foi utilizado. Uma vez que indivíduos alcoólatras geralmente apresentam comprometimento hepatobiliar, a associação entre gama-glutamil transpeptidase (GGT s

  6. Prenatal exposure to anticonvulsants and psychosexual development

    NARCIS (Netherlands)

    Dessens, A. B.; Cohen-Kettenis, P. T.; Mellenbergh, G. J.; vd Poll, N.; Koppe, J. G.; Boer, K.

    1999-01-01

    Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in

  7. A exposição ao chumbo como fator de risco para alterações no desenvolvimento da linguagem Lead exposure as a risk factor for alterations in language development

    Directory of Open Access Journals (Sweden)

    Mariana San Jorge

    2008-06-01

    Full Text Available OBJETIVO: Verificar a ocorrência de alterações no desenvolvimento, em particular, o desenvolvimento da linguagem, em crianças com histórico de exposição ao metal chumbo, e a existência ou não de correlação entre índice de contaminação e desenvolvimento de linguagem. MÉTODOS: Cinqüenta e oito crianças entre 12 e 36 meses foram submetidas à triagem fonoaudiológica; destas, 15 compareceram para avaliação específica por meio da Escala de Desenvolvimento Comportamental de Gesell e Amatruda por terem falhado na triagem. A correlação entre índice de chumbo e o grau de defasagem na linguagem foi verificada. RESULTADOS: Seis crianças apresentaram defasagem na área da linguagem da Escala, sendo que, uma delas apresentou defasagem em todos os campos. CONCLUSÃO: Não foi encontrada correlação negativa significante entre a concentração de chumbo e o grau de defasagem no desenvolvimento de linguagem dos indivíduos participantes, entretanto, o estudo sugere que a contaminação pelo chumbo tornou-se fator de risco para alterações no desenvolvimento da linguagem destas crianças. Dessa forma, mais estudos são necessários para verificar o grau de prejuízo que este metal pode ocasionar às pessoas, principalmente quando estão em desenvolvimento.PURPOSE: To verify the occurrence of alterations in the development, in particular language development, in children with history of metal lead exposure, and whether there is a correlation between index of contamination and language development. METHODS: Fifty eight children with ages between 12 and 36 months were submitted to speech-language pathology screening; 15 of these children failed the screening, and were referred to specific evaluation using the Behavioral Development Scale by Gesell and Amatruda (Escala de Desenvolvimento Comportamental de Gesell e Amatruda. The correlation between lead index and the degree of language deficits was verified. RESULTS: Six children presented

  8. Aquisition of age- and sex-dependent patient data for the calculation of annual radiation exposure in nuclear medicine: a German pilot study; Erfassung alters- und geschlechtsbezogener Daten nuklearmedizinischer Untersuchungen zur Berechnung der jaehrlichen Strahlenexposition in der BRD: Eine Pilotstudie

    Energy Technology Data Exchange (ETDEWEB)

    Schnell-Inderst, P.; Hacker, M.; Weiss, M.; Hahn, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum der Univ. Muenchen (Germany); Nosske, D.; Stamm-Meyer, A.; Brix, G. [Bundesamt fuer Strahlenschutz, Inst. fuer Strahlenhygiene, Neuherberg (Germany)

    2004-04-01

    Aim: a pilote study for estimation of radiation exposure due to diagnostic procedures in nuclear medicine using routine data of hospitals and practices in Germany. Methods: hospitals and practices willing to participate in the study supplied data of one year (1997), containing information on patients' identification number, age, sex, type of diagnostic procedure, radiopharmaceutical, administered activity, type of health insurance (private/public), inpatient/outpatient status, and so-called leistungsziffer, which describes the type of medical performances in Germany. The effective dose per examination was calculated according to ICRP 80. Mean, standard deviation, median, 5{sup th} and 95{sup th} percentiles of the effective dose were calculated, stratified by type of organ system and also by sex and age, including patients of {>=} 18 years. Results: 82 039 examinations from patients of 9 hospitals and practices were analyzed. The median (5-95{sup th} percentiles) of the effective dose per examination for all patients was 2.9 mSv (0.4-8.5 mSv); 1.2 examinations per patient and year were performed on average. The three most frequent examinations were bone scans (median 3.4 mSv; 2.9-5.1), thyroid (0.9 mSv; 0.4-2.2) and cardiovascular studies (7.3 mSv; 3.8-20.2). The median effective dose for 18 to 40 years old women was 1.0 mSv (0.4-5.8), for women between 41 and 65 years 2.2 mSv (0.4-7.3) and for women older than 65 years 2.4 mSv (0.5-7.6). The corresponding values for men were 2.6 mSv (0.3-7.6); 3.3 mSv (0.4-9.1), and 3.4 mSv (0.5-8.8). Conclusion: it was possible to gain an accurate determination of radiation exposure of diagnostic procedures in nuclear medicine by routine data. (orig.) [German] Ziel: Pilotstudie zur Ermittlung der Strahlenexposition in Deutschland bei Untersuchungen in der nuklearmedizinischen Diagnostik anhand von Routinedaten aus Kliniken und Praxen. Methoden: Kliniken und Praxen in Deutschland lieferten 1997 routinemaessig erhobene

  9. Exposure Forecaster

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

  10. Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

    2018-01-01

    Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure