Low-Level Environmental Phthalate Exposure Associates with Urine Metabolome Alteration in a Chinese Male Cohort.

PubMed

Zhang, Jie; Liu, Liangpo; Wang, Xiaofei; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2016-06-07

The general population is exposed to phthalates through various sources and routes. Integration of omics data and epidemiological data is a key step toward directly linking phthalate biomonitoring data with biological response. Urine metabolomics is a powerful tool to identify exposure biomarkers and delineate the modes of action of environmental stressors. The objectives of this study are to investigate the association between low-level environmental phthalate exposure and urine metabolome alteration in male population, and to unveil the metabolic pathways involved in the mechanisms of phthalate toxicity. In this retrospective cross-sectional study, we studied the urine metabolomic profiles of 364 male subjects exposed to low-level environmental phthalates. Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are the most widely used phthalates. ∑DEHP and MBP (the major metabolite of DBP) were associated with significant alteration of global urine metabolome in the male population. We observed significant increase in the levels of acetylneuraminic acid, carnitine C8:1, carnitine C18:0, cystine, phenylglycine, phenylpyruvic acid and glutamylphenylalanine; and meanwhile, decrease in the levels of carnitine C16:2, diacetylspermine, alanine, taurine, tryptophan, ornithine, methylglutaconic acid, hydroxyl-PEG2 and keto-PGE2 in high exposure group. The observations indicated that low-level environmental phthalate exposure associated with increased oxidative stress and fatty acid oxidation and decreased prostaglandin metabolism. Urea cycle, tryptophan and phenylalanine metabolism disruption was also observed. The urine metabolome disruption effects associated with ∑DEHP and MBP were similar, but not identical. The multibiomarker models presented AUC values of 0.845 and 0.834 for ∑DEHP and MBP, respectively. The predictive accuracy rates of established models were 81% for ΣDEHP and 73% for MBP. Our results suggest that low-level environmental phthalate exposure associates with urine metabolome disruption in male population, providing new insight into the early molecular events of phthalate exposure.

Alteration of adenyl dinucleotide metabolism by environmental stress.

PubMed Central

Baker, J C; Jacobson, M K

1986-01-01

Exposure of cultured mammalian cells to a variety of conditions that induce the synthesis of stress proteins, including hyperthermia, ethanol, cadmium, and arsenite resulted in an increased cellular content of adenyl dinucleotides including diadenosine tetraphosphate (Ap4A). Exposure to other agents that cause metabolic perturbations not known to induce the synthesis of stress proteins, such as cyclohexamide, cytosine arabinoside, hydroxyurea, and ultraviolet irradiation did not alter the content of these nucleotides. It is proposed that these unique nucleotides may mediate adaptive responses of mammalian cells to environmental stress. PMID:3458199

Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

PubMed Central

Roy, Deodutta; Morgan, Marisa; Yoo, Changwon; Deoraj, Alok; Roy, Sandhya; Yadav, Vijay Kumar; Garoub, Mohannad; Assaggaf, Hamza; Doke, Mayur

2015-01-01

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors. PMID:26512648

CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

EPA Science Inventory

Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

Epigenomics in Environmental Health

PubMed Central

Christensen, Brock C.; Marsit, Carmen J.

2011-01-01

This review considers the emerging relationships between environmental factors and epigenetic alterations and the application of genome-wide assessments to better define these relationships. First we will briefly cover epigenetic programming in development, one-carbon metabolism, and exposures that may disrupt normal developmental programming of epigenetic states. In addition, because a large portion of epigenetic research has focused on cancer, we discuss exposures associated with carcinogenesis including asbestos, alcohol, radiation, arsenic, and air pollution. Research on other exposures that may affect epigenetic states such as endocrine disruptors is also described, and we also review the evidence for epigenetic alterations associated with aging that may reflect cumulative effects of exposures. From this evidence, we posit potential mechanisms by which exposures modify epigenetic states, noting that understanding the true effect of environmental exposures on the human epigenome will require additional research with appropriate epidemiologic studies and application of novel technologies. With a more comprehensive understanding of the affects of exposures on the epigenome, including consideration of genetic background, the prediction of the toxic potential of new compounds may be more readily achieved, and may lead to the development of more personalized disease prevention and treatment strategies. PMID:22303378

In utero and postnatal exposure to arsenic alters pulmonary structure and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lantz, R. Clark; Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721; BIO5 Institute, University of Arizona, Tucson, AZ 85721

2009-02-15

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airwaymore » reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.« less

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

PubMed

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Endocrine effects of prenatal exposure to PCBs, dioxins, and other xenobiotics: implications for policy and future research.

PubMed Central

Birnbaum, L S

1994-01-01

Recent reports have suggested that environmental chemicals may be associated with endocrine alterations in people, wildlife, and experimental animals. Pharmacological investigations as well as natural poisoning episodes have led to the association between exogenous chemicals and alterations in multiple hormonal systems. Persistent environmental contaminants such as dioxins and PCBs have been shown to modulate the activities of several different hormones. The unborn child or the neonate may be at special risk from these chemicals because of rapid growth and development, in addition to enhanced exposure. Because most exposure to these persistent chemicals is via food, changes in dietary habits and/or reduced contamination of the food supply may be required. PMID:7895708

Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

PubMed Central

Gilbert, Kathleen M.; Woodruff, William; Blossom, Sarah J.

2014-01-01

Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. PMID:24696780

Epigenetics, obesity and early-life cadmium or lead exposure.

PubMed

Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

2017-01-01

Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

Default mode network connectivity as a function of familial and environmental risk for psychotic disorder.

PubMed

Peeters, Sanne C T; van de Ven, Vincent; Gronenschild, Ed H B M; Patel, Ameera X; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld

2015-01-01

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.

A cross-study analysis of prenatal exposures to environmental contaminants and the epigenome: support for stress-responsive transcription factor occupancy as a mediator of gene-specific CpG methylation patterning

PubMed Central

Martin, Elizabeth M.; Fry, Rebecca C.

2016-01-01

Abstract A biological mechanism by which exposure to environmental contaminants results in gene-specific CpG methylation patterning is currently unknown. We hypothesize that gene-specific CpG methylation is related to environmentally perturbed transcription factor occupancy. To test this hypothesis, a database of 396 genes with altered CpG methylation either in cord blood leukocytes or placental tissue was compiled from 14 studies representing assessments of six environmental contaminants. Subsequently, an in silico approach was used to identify transcription factor binding sites enriched among the genes with altered CpG methylation in relationship to the suite of environmental contaminants. For each study, the sequences of the promoter regions (representing −1000 to +500 bp from the transcription start site) of all genes with altered CpG methylation were analyzed for enrichment of transcription factor binding sites. Binding sites for a total of 56 unique transcription factors were identified to be enriched within the promoter regions of the genes. Binding sites for the Kidney-Enriched Krupple-like Factor 15, a known responder to endogenous stress, were enriched ( P  < 0.001–0.041) among the genes with altered CpG methylation associated for five of the six environmental contaminants. These data support the transcription factor occupancy theory as a potential mechanism underlying environmentally-induced gene-specific CpG methylation. PMID:27066266

Environmental Alterations of Epigenetics Prior to the Birth

PubMed Central

Lo, Chiao-Ling; Zhou, Feng C.

2014-01-01

The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, non-coding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late onset neuropsychiatric diseases, or idiosyncratic mental disorders. PMID:25131541

Environmental alterations of epigenetics prior to the birth.

PubMed

Lo, Chiao-Ling; Zhou, Feng C

2014-01-01

The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, noncoding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late-onset neuropsychiatric diseases, or idiosyncratic mental disorders. © 2014 Elsevier Inc. All rights reserved.

Exposure to Environmentally Relevant Doses of the Xenoestrogen Bisphenol-A Alters Development of the Fetal Mouse Mammary Gland

PubMed Central

Vandenberg, Laura N.; Maffini, Maricel V.; Wadia, Perinaaz R.; Sonnenschein, Carlos; Rubin, Beverly S.; Soto, Ana M.

2010-01-01

Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials, food and beverage containers, and other plastic consumer products. Effects of perinatal BPA exposure on the mouse mammary gland have been observed in puberty and adulthood, long after the period of exposure has ended. The aim of this study was to examine fetal mammary gland development at embryonic day (E)18 and assess changes in the tissue organization and histoarchitecture after exposure to an environmentally relevant dose of BPA. In unexposed fetuses, the relative position of the fetus with respect to its female and male siblings in the uterus influenced growth of the ductal tree, which was more developed in females placed between two males than in females placed between two females. Exposure of dams to 250 ng BPA per kilogram body weight per day from E8 to E18 significantly increased ductal area and ductal extension in exposed fetuses and obliterated positional differences. In the stroma, BPA exposure promoted maturation of the fat pad and altered the localization of collagen. Within the epithelium, BPA exposure led to a decrease in cell size and delayed lumen formation. Because mammary gland development is dependent on reciprocal interactions between these compartments, the advanced maturation of the fat pad and changes in the extracellular matrix may be responsible for the altered growth, cell size, and lumen formation observed in the epithelium. These results suggest that alterations in mammary gland phenotypes observed at puberty and adulthood in perinatally exposed mice have their origins in fetal development. PMID:17023525

Epigenetics, obesity and early-life cadmium or lead exposure

PubMed Central

Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

2017-01-01

Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures. PMID:27981852

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

PubMed

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.

BLOOD LEAD CONCENTRATION AND DELAYED PUBERTY IN GIRLS

EPA Science Inventory

Background
Environmental lead exposure has been linked to alterations in growth and endocrine function. It is not known whether such exposure affects pubertal development.

Methods
We analyzed the relations between blood lead concentration and pubertal...

Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens.

PubMed Central

Newbold, R

1995-01-01

Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. PMID:8593881

Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

PubMed Central

Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

2014-01-01

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

Long-term effects of early-life exposure to environmental oestrogens on ovarian function: role of epigenetics.

PubMed

Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M

2014-09-01

Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.

PubMed

Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

2017-01-01

Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products - methyl paraben (MPB) and triclosan (TCS) - on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson's Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in Mammary Histology and Transcriptome Profiles by Low-Dose Exposure to Environmental Phenols at Critical Windows of Development1

PubMed Central

Gopalakrishnan, Kalpana; Teitelbaum, Susan L.; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

2016-01-01

Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products – methyl paraben (MPB) and triclosan (TCS) – on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson’s Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. PMID:27810681

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

PubMed Central

Peeters, Sanne C. T.; van de Ven, Vincent; Gronenschild, Ed H. B. M; Patel, Ameera X.; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld

2015-01-01

Background Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Methods Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. Results There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Discussion Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure. PMID:25790002

ATR-FTIR spectroscopy reveals polycyclic aromatic hydrocarbon contamination despite relatively pristine site characteristics: Results of a field study in the Niger Delta.

PubMed

Obinaju, Blessing E; Martin, Francis L

2016-01-01

Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub-lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant (P<0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Amphibian Population Sensitivity to Environmental and Anthropogenic Impacts on Larval Development and Survival

EPA Science Inventory

Anticipating chronic effects of contaminant exposure on amphibian species is complicated both by toxicological and ecological uncertainty. Data for both chemical exposures and amphibian vital rates, including altered growth, are sparse. Developmental plasticity in amphibians fu...

Role of Autonomic Reflex Arcs in Cardiovascular Responses to Air Pollution Exposure

EPA Science Inventory

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome ...

The Contribution of Fetal Drug Exposure to Temperament: Potential Teratogenic Effects on Neuropsychiatric Risk

ERIC Educational Resources Information Center

Weiss, Sandra J.; St. Jonn-Seed, Mary; Harris-Muchell, Carolyn

2007-01-01

Background: Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. Methods: High risk children (n = 120) were followed from…

An Evaluation of Gestational Exposure to Perfluorooctanoic Acid (PFOA): Effects on Body Composition and Physiological Factors

EPA Science Inventory

Exposure to environmental pollutants can be a factor for induction of metabolic disorders. This study examined if exposure to PFOA during development could alter body composition and other physiological outcomes. Study 1: Pregnant CD-1 mice were gavaged with PFOA at 0,0.001,0.01,...

LOW DOSE PESTICIDE EXPOSURE AND ALTERED REPRODUCTIVE SYSTEM DEVELOPMENT IN REPTILES

EPA Science Inventory

In: Environmental Sciences in the 21st Century: Paradigms, Opportunities, and Challenges: Abstract Book: SETAC 21st Annual Meeting, 12-16 November 2000, Nashville, TN. Society of Environmental Toxicology and Chemistry, Pensacola, FL. Pp. 99.

Role of Environmental Contaminants in the Etiology of Alzheimer's Disease: A Review

PubMed Central

Manivannan, Yegambaram; Manivannan, Bhagyashree; Beach, Thomas G.; Halden, Rolf U.

2015-01-01

Alzheimer's dis ease (AD) is a leading cause of mortality in the developed world with 70% risk attributable to genetics. The remaining 30% of AD risk is hypothesized to include environmental factors and human lifestyle patterns. Environmental factors possibly include inorganic and organic hazards, exposure to toxic metals (aluminium, copper), pesticides (organochlorine and organophosphate insecticides), industrial chemicals (flame retardants) and air pollutants (particulate matter). Long term exposures to these environmental contaminants together with bioaccumulation over an individual's life-time are speculated to induce neuroinflammation and neuropathology paving the way for developing AD. Epidemiologic associations between environmental contaminant exposures and AD are still limited. However, many in vitro and animal studies have identified toxic effects of environmental contaminants at the cellular level, revealing alterations of pathways and metabolisms associated with AD that warrant further investigations. This review provides an overview of in vitro, animal and epidemiological studies on the etiology of AD, highlighting available data supportive of the long hypothesized link between toxic environmental exposures and development of AD pathology. PMID:25654508

Environmental noise pollution in the United States: developing an effective public health response.

PubMed

Hammer, Monica S; Swinburn, Tracy K; Neitzel, Richard L

2014-02-01

Tens of millions of Americans suffer from a range of adverse health outcomes due to noise exposure, including heart disease and hearing loss. Reducing environmental noise pollution is achievable and consistent with national prevention goals, yet there is no national plan to reduce environmental noise pollution. We aimed to describe some of the most serious health effects associated with noise, summarize exposures from several highly prevalent noise sources based on published estimates as well as extrapolations made using these estimates, and lay out proven mechanisms and strategies to reduce noise by incorporating scientific insight and technological innovations into existing public health infrastructure. We estimated that 104 million individuals had annual LEQ(24) levels > 70 dBA (equivalent to a continuous average exposure level of >70 dBA over 24 hr) in 2013 and were at risk of noise-induced hearing loss. Tens of millions more may be at risk of heart disease, and other noise-related health effects. Direct regulation, altering the informational environment, and altering the built environment are the least costly, most logistically feasible, and most effective noise reduction interventions. Significant public health benefit can be achieved by integrating interventions that reduce environmental noise levels and exposures into the federal public health agenda.

BIOCHEMICAL INDICES OF EXPOSURE TO ENVIRONMENTAL ESTROGENS: A SPECIES COMPARISON

EPA Science Inventory

Existence of endocrine active substances in the aquatic environment has been clearly established in several studies. Exposure of organisms to both natural and synthetic xenoestrogens have been found to alter biochemical homeostatis and, in some cases, result in reproductive and d...

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.

PubMed

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2017-03-01

Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

PubMed Central

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2016-01-01

Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360 PMID:27634282

The impact of environmental stress on male reproductive development in plants: biological processes and molecular mechanisms

PubMed Central

de Storme, Nico; Geelen, Danny

2014-01-01

In plants, male reproductive development is extremely sensitive to adverse climatic environments and (a)biotic stress. Upon exposure to stress, male gametophytic organs often show morphological, structural and metabolic alterations that typically lead to meiotic defects or premature spore abortion and male reproductive sterility. Depending on the type of stress involved (e.g. heat, cold, drought) and the duration of stress exposure, the underlying cellular defect is highly variable and either involves cytoskeletal alterations, tapetal irregularities, altered sugar utilization, aberrations in auxin metabolism, accumulation of reactive oxygen species (ROS; oxidative stress) or the ectopic induction of programmed cell death (PCD). In this review, we present the critically stress-sensitive stages of male sporogenesis (meiosis) and male gametogenesis (microspore development), and discuss the corresponding biological processes involved and the resulting alterations in male reproduction. In addition, this review also provides insights into the molecular and/or hormonal regulation of the environmental stress sensitivity of male reproduction and outlines putative interaction(s) between the different processes involved. PMID:23731015

Environment, susceptibility windows, development and child health

PubMed Central

Wright, Robert O

2017-01-01

Purpose To illustrate the role of the exposome in child health while highlighting unique aspects of this research pertinent to children, such as the time dependency of environmental exposures on fetal programming, as well as the time dependent nature of child behavior, diet, and motor function, which alter the probability of exposure to different compounds. Future environmental health research will be more hypothesis generating but will also need to heed lessons learned from other “omic” sciences. The NIH Child Health Environmental Analysis Resource (CHEAR) is a major step towards providing the infrastructure needed to study the exposome and child health. Recent Findings Environmental exposures have overlapping mechanisms such as endocrine disruption and oxidative stress among others. The nature of the long term health impact of an exposure is dependent not only on dose, but also on the timing of exposure. Advances in exposure science, toxicology and biostatistics will create new opportunities to identify and better define windows of susceptibility to environmental exposures. Summary As exposure science matures, we will better understand the role of environment on health. Linking the exposome with genomics will unlock the root origins of multiple complex diseases. PMID:28107208

Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma

PubMed Central

Venza, Mario; Visalli, Maria; Biondo, Carmelo; Oteri, Rosaria; Agliano, Federica; Morabito, Silvia; Caruso, Gerardo; Caffo, Maria; Teti, Diana; Venza, Isabella

2014-01-01

Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation. PMID:25646071

Developmental Exposure to PCBs Differentially Alters Sensitivity to Audiogenic and Kindling-Induced Seizures in Rats

EPA Science Inventory

Previously we reported an increased incidence of audiogenic seizures in offspring of pregnant rats exposed to an environmental mixture of polychlorinated biphenyls (PCBs). This study compares the proconvulsant properties of PCB exposure in audiogenic and electrical kindling seizu...

Developmental exposure to polychlorinated biphenyls (PCBs) interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats.

EPA Science Inventory

BACKGROUND: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures ...

The intersection of stress, drug abuse and development.

PubMed

Thadani, Pushpa V

2002-01-01

Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

Impact of low-dose chronic exposure to Bisphenol A (BPA) on adult male zebrafish adaption to the environmental complexity: Disturbing the color preference patterns and reliving the anxiety behavior.

PubMed

Li, Xiang; Sun, Ming-Zhu; Li, Xu; Zhang, Shu-Hui; Dai, Liang-Ti; Liu, Xing-Yu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2017-11-01

The extensive usage of xenobiotic endocrine disrupting chemicals (XEDCs), such as Bisphenol A (BPA), has created obvious threat to aquatic ecosystems worldwide. Although a comprehensive understanding of the adverse effect of BPA on behaviors and physiology have been proven, the potential impact of low-dose BPA on altering the basic ability of aquatic organism in adapting to the surrounded complex environment still remains elusive. In this research, we report that treatment of adult male zebrafish with chronic (7 weeks) low-dose (0.22 nM-2.2 nM) BPA, altered the ability in adapting the complex environment by disturbing the natural color preference patterns. In addition, chronic 50 ng/L (0.22 nM) BPA exposure alleviated the anxiety behavior of male zebrafish confronted with the novel environment by enhancing the preference towards light in the light/dark preference test. This phenotype was associated with less expression of serotonin (5-TH) in the hypothalamus and the down-regulation of tyrosine hydroxylase (TH) in brain tissues. As such, our results show that low-dose BPA remnant in surface waters altered zebrafish behavior that are known to have ecological and evolutionary consequences. Here we reported that the impact of chronic low-dose BPA exposure on the basic capability of zebrafish to adapt to the environmental complexity. Specifically, BPA at low concentration, under the environmental safety level and 3000-fold lower than the accepted human daily exposure, interfered with the ability to discriminate color and alleviate anxiety induced by the novel environment, which finally altered the capability of male zebrafish to adapt to the environmental complexity. These findings revealed the ecological effect of low-dose BPA and regular BPA concentration standard are not necessarily safe. The result also provided the consideration of retuning the hazard concentration level of BPA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

PubMed Central

Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

2014-01-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Yi; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721; Tao, Shasha

2012-12-15

Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted inmore » pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.« less

Neuroendocrine host factors and inflammatory disease susceptibility.

PubMed Central

Ligier, S; Sternberg, E M

1999-01-01

The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. PMID:10502534

Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf

USGS Publications Warehouse

Schoenfuss, H.L.; Bartell, S.E.; Bistodeau, T.B.; Cediel, R.A.; Grove, K.J.; Zintek, Larry; Lee, K.E.; Barber, L.B.

2008-01-01

The synthetic organic compound 4-nonylphenol (NP) has been detected in many human-impacted surface waters in North America. In this study, we examined the ability of NP to alter reproductive competence in male fathead minnows after a 28 day flow-through exposure in a range of environmentally relevant concentrations bracketing the U.S. Environmental Protection Agency toxicity-based NP chronic exposure criterion of 6.1 ??g NP/L. Exposure to NP at and above the EPA chronic exposure criterion resulted in an induction of plasma vitellogenin (VTG) within 14 days. However, 7 days after the cessation of exposure, VTG concentrations had dropped more than 50% and few males expressed VTG above the detection threshold. All of the morphological endpoints, including gonadosomatic index, hepatosomatic index, secondary sexual characters, and histopathology, were unaltered by all NP treatments. However, when NP-exposed male fish were allowed to compete with control males for access to nest sites and females, most treatments altered the reproductive competence of exposed males. At lower NP concentrations, exposed males out-competed control males, possibly by being primed through the estrogenic NP exposure in a fashion similar to priming by pheromones released from female fathead minnows. At higher NP exposure concentrations, this priming effect was negated by the adverse effects of the exposure and control males out-competed treated males. Results of this study indicate the complexity of endocrine disrupting effects and the need for multiple analysis levels to assess the effects of these compounds on aquatic organisms. ?? 2007 Elsevier B.V. All rights reserved.

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

EPA Science Inventory

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...

Environmental endocrine disruption in decapod crustacean larvae: hormone titers, cytochrome P450, and stress protein responses to heptachlor exposure.

PubMed

Snyder, M J; Mulder, E P

2001-11-12

A variety of enzymes and other proteins are produced by organisms in response to xenobiotic exposures. Cytochrome P450s (CYP) are one of the major phase I-type classes of detoxification enzymes found in terrestrial and aquatic organisms ranging from bacteria to vertebrates. One of the primary functions of stress proteins (HSPs) is to aid in the recovery of damaged proteins by chaperoning their refolding. These and other biomarkers of xenobiotic exposure and resulting effects have not been studied in crustacean larvae. This information is of potential importance for environmental management and risk assessment. In this work, we have given Homarus americanus larvae single 24 h exposures to the cyclodiene pesticide heptachlor, a known environmental endocrine disruptor (EDC) on different days of the 1st larval instar. We followed these larvae during the first larval stage for effects on timing of ecdysis to 2nd stage, ecdysteroid molting hormone titers, and alterations in the levels of cytochrome P450 CYP45 and HSP70 proteins. Delays in ecdysis were correlated with alterations in ecdysteroid levels. This result provides clues that this pesticide may function as an environmental endocrine disruptor in crustaceans. CYP45 and HSP70 levels were significantly elevated for several days following heptachlor exposure. The elevation in HSP70 was prolonged depending on the day of pesticide exposure and this was directly related to the increase in mortality. These results demonstrate the utility of these measurements as potential biomarkers in crustacean larval developmental toxicology and EDC effects research.

Environmental epigenetics: a role in endocrine disease?

PubMed

Fleisch, Abby F; Wright, Robert O; Baccarelli, Andrea A

2012-10-01

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.

Pollution Comes Home and Gets Personal: Women's Experience of Household Chemical Exposure*

PubMed Central

Altman, Rebecca Gasior; Morello-Frosch, Rachel; Brody, Julia Green; Rudel, Ruthann; Brown, Phil; Averick, Mara

2009-01-01

We report on interviews conducted with participants in a novel study about environmental chemicals in body fluids and household air and dust. Interviews reveal how personal and collective environmental history influence the interpretation of exposure data, and how participants fashion an emergent understanding of environmental health problems from the articulation of science and experience. To the illness experience literature, we contribute a framework for analyzing a new category of embodied narratives—“exposure experience”—that examines the mediating role of science. We update social scientific knowledge about social responses to toxic chemicals during a period in which science alters public understanding of chemical pollution. This article is among the first published accounts of participants' responses to learning personal exposure data, research identified as critical to environmental science and public health. Our findings raise the importance of reporting even uncertain science and underscore the value of a community-based reporting strategy. PMID:19181047

Exposure of honey bees (Apis mellifera) to different classes of insecticides exhibit distinct molecular effect patterns at concentrations that mimic environmental contamination.

PubMed

Christen, Verena; Fent, Karl

2017-07-01

Pesticides are implicated in the decline of honey bee populations. Many insecticides are neurotoxic and act by different modes of actions. Although a link between insecticide exposure and changed behaviour has been made, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic concentrations of two organophosphates, chlorpyrifos and malathion, the pyrethroid cypermethrin, and the ryanodine receptor activator, chlorantraniliprole. We assessed transcriptional alterations of selected genes at three exposure times (24 h, 48 h, 72 h) in caged honey bees exposed to different concentrations of these compounds. Our targeted gene expression concept focused on several transcripts, including nicotinic acetylcholine receptor α 1 and α 2 (nAChRα1, nAChRα2) subunits, the multifunctional gene vitellogenin, immune system related genes of three immune system pathways, genes belonging to the detoxification system and ER stress genes. Our data indicate a dynamic pattern of expressional changes at different exposure times. All four insecticides induced strong alterations in the expression of immune system related genes suggesting negative implications for honey bee health, as well as cytochrome P450 enzyme transcripts suggesting an interference with metabolism. Exposure to neurotoxic chlorpyrifos, malathion and cypermethrin resulted in up-regulation of nAChRα1 and nAChRα2. Moreover, alterations in the expression of vitellogenin occurred, which suggests implications on foraging activity. Chlorantraniliprole induced ER stress which may be related to toxicity. The comparison of all transcriptional changes indicated that the expression pattern is rather compound-specific and related to its mode of action, but clusters of common transcriptional changes between different compounds occurred. As transcriptional alterations occurred at environmental concentrations our data provide a molecular basis for observed adverse effects of these insecticides to bees. Copyright © 2017 Elsevier Ltd. All rights reserved.

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

PubMed

El Sheikh Saad, H; Toullec, A; Vacher, S; Pocard, M; Bieche, I; Perrot-Applanat, M

2013-02-01

Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

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

PubMed Central

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

The effects of migrant remittances on population–environment dynamics in migrant origin areas: international migration, fertility, and consumption in highland Guatemala

PubMed Central

Lopez-Carr, David

2010-01-01

International migration impacts origin regions in many ways. As examples, remittances from distant migrants may alter consumption patterns within sending communities, while exposure to different cultural norms may alter other behaviors. This paper combines these insights to offer a unique lens on migration’s environmental impact. From an environmental perspective, we ask the following question: is the likely rise in consumption brought about by remittances counterbalanced by a reduction in fertility in migrant households following exposure to lower fertility cultures? Based on ethnographic case studies in two western highland Guatemalan communities, we argue that the near-term rise in consumption due to remittances is not counterbalanced by rapid decline in migrant household fertility. However, over time, the environmental cost of consumption may be mitigated at the community level through diffusion of contraception and family planning norms yielding lower family size. PMID:21258636

Environmental Noise Pollution in the United States: Developing an Effective Public Health Response

PubMed Central

Hammer, Monica S.; Swinburn, Tracy K.

2013-01-01

Background: Tens of millions of Americans suffer from a range of adverse health outcomes due to noise exposure, including heart disease and hearing loss. Reducing environmental noise pollution is achievable and consistent with national prevention goals, yet there is no national plan to reduce environmental noise pollution. Objectives: We aimed to describe some of the most serious health effects associated with noise, summarize exposures from several highly prevalent noise sources based on published estimates as well as extrapolations made using these estimates, and lay out proven mechanisms and strategies to reduce noise by incorporating scientific insight and technological innovations into existing public health infrastructure. Discussion: We estimated that 104 million individuals had annual LEQ(24) levels > 70 dBA (equivalent to a continuous average exposure level of >70 dBA over 24 hr) in 2013 and were at risk of noise-induced hearing loss. Tens of millions more may be at risk of heart disease, and other noise-related health effects. Direct regulation, altering the informational environment, and altering the built environment are the least costly, most logistically feasible, and most effective noise reduction interventions. Conclusion: Significant public health benefit can be achieved by integrating interventions that reduce environmental noise levels and exposures into the federal public health agenda. Citation: Hammer MS, Swinburn TK, Neitzel RL. 2014. Environmental noise pollution in the United States: developing an effective public health response. Environ Health Perspect 122:115–119; http://dx.doi.org/10.1289/ehp.1307272 PMID:24311120

Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior

PubMed Central

Skinner, Michael K.; Anway, Matthew D.; Savenkova, Marina I.; Gore, Andrea C.; Crews, David

2008-01-01

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease. PMID:19015723

Environmental signals and transgenerational epigenetics

PubMed Central

Skinner, Michael K; Guerrero-Bosagna, Carlos

2010-01-01

The ability of an environmental factor or toxicant to promote a phenotype or disease state not only in the individual exposed, but also in subsequent progeny for multiple generations, is termed transgenerational inheritance. The majority of environmental agents do not promote genetic mutations or alterations in DNA sequence, but do have the capacity to alter the epigenome. Although most environmental exposures will influence somatic cells and not allow the transgenerational transmission of a phenotype, the ability of an environmental factor to reprogram the germline epigenome can promote a transgenerational inheritance of phenotypes and disease states. A limited number of critical developmental periods exist when environmental signals can produce a significant epigenetic reprogramming of the germline. In this review, the ability of environmental factors or toxicants to promote epigenetic transgenerational phenotypes is reviewed. PMID:20563319

Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

EPA Science Inventory

Biological monitoring has become a standard approach to exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. Recently, nephrotoxicant research us...

Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas.

PubMed

Frenzilli, Giada; Ryskalin, Larisa; Ferrucci, Michela; Cantafora, Emanuela; Chelazzi, Silvia; Giorgi, Filippo S; Lenzi, Paola; Scarcelli, Vittoria; Frati, Alessandro; Biagioni, Francesca; Gambardella, Stefano; Falleni, Alessandra; Fornai, Francesco

2017-01-01

Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days) after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise.

Impact of climate change on occupational exposure to solar radiation.

PubMed

Grandi, Carlo; Borra, Massimo; Militello, Andrea; Polichetti, Alessandro

2016-01-01

Occupational exposure to solar radiation may induce both acute and long-term effects on skin and eyes. Personal exposure is very difficult to assess accurately, as it depends on environmental, organisational and individual factors. The ongoing climate change interacting with stratospheric ozone dynamics may affect occupational exposure to solar radiation. In addition, tropospheric levels of environmental pollutants interacting with solar radiation may be altered by climate dynamics, so introducing another variable affecting the overall exposure to solar radiation. Given the uncertainties regarding the direction of changes in exposure to solar radiation due to climate change, compliance of outdoor workers with protective measures and a proper health surveillance are crucial. At the same time, education and training, along with the promotion of healthier lifestyles, are of paramount importance.

Predicting Risks to Wildlife Populations from Multriple Stressors: Mercury, Habitat Alteration and Common Loon Breeding in New Hampshire, USA

EPA Science Inventory

We applied a generic approach to estimate and test predictions of population risks of mercury (Hg) exposure and habitat alteration on common loons (Gavia immer) breeding in New Hampshire (NH), USA. We developed a publically-accessible data system, integrating environmental data ...

Environmental estrogens alter early development in Xenopus laevis.

PubMed

Bevan, Cassandra L; Porter, Donna M; Prasad, Anita; Howard, Marthe J; Henderson, Leslie P

2003-04-01

A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.

The antidepressant fluoxetine alters mechanisms of pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki).

PubMed

Bertram, Michael G; Ecker, Tiarne E; Wong, Bob B M; O'Bryan, Moira K; Baumgartner, John B; Martin, Jake M; Saaristo, Minna

2018-03-19

Contamination of aquatic habitats with pharmaceuticals is a major environmental concern. Recent studies have detected pharmaceutical pollutants in a wide array of ecosystems and organisms, with many of these contaminants being highly resistant to biodegradation and capable of eliciting sub-lethal effects in non-target species. One such pollutant is fluoxetine, a widely prescribed antidepressant, which is frequently detected in surface waters globally and can alter physiology and behaviour in aquatic organisms. Despite this, relatively little is known about the potential for fluoxetine to disrupt mechanisms of sexual selection. Here, we investigate the impacts of 30-day exposure to two environmentally realistic levels of fluoxetine (low and high) on mechanisms of pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki). We tested 1) male mating behaviour in the absence or presence of a competitor male, and 2) sperm quality and quantity. We found that high-fluoxetine exposure increased male copulatory behaviour in the absence of a competitor, while no effect was detected under male-male competition. Further, fluoxetine exposure at both concentrations increased total sperm count relative to males from the control group, while no significant change in sperm quality was observed. Lastly, low-fluoxetine males showed a significant reduction in condition index (mass relative to length). Our study is the first to show altered mechanisms of both pre- and post-copulatory sexual selection in an aquatic species resulting from environmentally realistic fluoxetine exposure, highlighting the capacity of pharmaceutical pollution to interfere with sensitive reproductive processes in wildlife. Copyright © 2018 Elsevier Ltd. All rights reserved.

Research review. Interactions between environmental chemicals and drug biotransformation in man.

PubMed

Alvares, A P

1978-01-01

Many factors influence the metabolism of drugs in man. Besides genetic factors, environmental factors may play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Intentional or unintentional exposure to environmental chemicals could enhance or inhibit the activity of hepatic mixed function oxidases that metabolise drugs and other foreign chemicals, as well as endogenous substrates such as steroid hormones. A major source of such exposure may be occupational. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides, and other halogenated hydrocarbons such as polychlorinated biphenyls, has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. A number of studies have shown that cigarette smoking can alter the pharmacological action and/or the metabolism of some drugs. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Data, which are not very conclusive, indicate that heavy marijuana use may have an inhibitory effect on metabolism of some drugs and an inducing effect on others such as theophylline. Dietary factors may also play a significant role in the regulation of drug metabolism. Charcoal broiling which introduces polycyclic hydrocarbons into foods has been shown to enhance the metabolism of the test drug, antipyrine, and of such commonly used drugs as phenacetin and theophylline. Such intentional or unintentional exposure to environmental chemicals which may alter the rates of drug metabolism in man indicates the importance of individualisation of drug therapy.

Postnatal Developmental Trajectories of Neural Circuits in the Primate Prefrontal Cortex: Identifying Sensitive Periods for Vulnerability to Schizophrenia

PubMed Central

Hoftman, Gil D.; Lewis, David A.

2011-01-01

Schizophrenia is a disorder of cognitive neurodevelopment with characteristic abnormalities in working memory attributed, at least in part, to alterations in the circuitry of the dorsolateral prefrontal cortex. Various environmental exposures from conception through adolescence increase risk for the illness, possibly by altering the developmental trajectories of prefrontal cortical circuits. Macaque monkeys provide an excellent model system for studying the maturation of prefrontal cortical circuits. Here, we review the development of glutamatergic and γ-aminobutyric acid (GABA)-ergic circuits in macaque monkey prefrontal cortex and discuss how these trajectories may help to identify sensitive periods during which environmental exposures, such as those associated with increased risk for schizophrenia, might lead to the types of abnormalities in prefrontal cortical function present in schizophrenia. PMID:21505116

Triclosan Exposure Is Associated with Rapid Restructuring of the Microbiome in Adult Zebrafish

PubMed Central

Barton, Carrie L.; Proffitt, Sarah; Tanguay, Robert L.; Sharpton, Thomas J.

2016-01-01

Growing evidence indicates that disrupting the microbial community that comprises the intestinal tract, known as the gut microbiome, can contribute to the development or severity of disease. As a result, it is important to discern the agents responsible for microbiome disruption. While animals are frequently exposed to a diverse array of environmental chemicals, little is known about their effects on gut microbiome stability and structure. Here, we demonstrate how zebrafish can be used to glean insight into the effects of environmental chemical exposure on the structure and ecological dynamics of the gut microbiome. Specifically, we exposed forty-five adult zebrafish to triclosan-laden food for four or seven days or a control diet, and analyzed their microbial communities using 16S rRNA amplicon sequencing. Triclosan exposure was associated with rapid shifts in microbiome structure and diversity. We find evidence that several operational taxonomic units (OTUs) associated with the family Enterobacteriaceae appear to be susceptible to triclosan exposure, while OTUs associated with the genus Pseudomonas appeared to be more resilient and resistant to exposure. We also found that triclosan exposure is associated with topological alterations to microbial interaction networks and results in an overall increase in the number of negative interactions per microbe in these networks. Together these data indicate that triclosan exposure results in altered composition and ecological dynamics of microbial communities in the gut. Our work demonstrates that because zebrafish afford rapid and inexpensive interrogation of a large number of individuals, it is a useful experimental system for the discovery of the gut microbiome’s interaction with environmental chemicals. PMID:27191725

Dim light at night disrupts molecular circadian rhythms and increases body weight.

PubMed

Fonken, Laura K; Aubrecht, Taryn G; Meléndez-Fernández, O Hecmarie; Weil, Zachary M; Nelson, Randy J

2013-08-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.

Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

PubMed

Martens, Dries S; Nawrot, Tim S

2016-09-01

Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies.

Strengthening Community Capacity to Participate in Making Decisions to Reduce Disproportionate Environmental Exposures

PubMed Central

Pastor, Manuel; Israel, Barbara

2011-01-01

Environmental exposures impose a disproportionate health burden on low-income populations and communities of color. One contributing factor may be the obstacles such communities face to full participation in making policy decisions about environmental health. This study described and analyzed the characteristics that contributed to communities' capacity to participate in making environmental decisions and suggested steps public agencies could take to achieve more meaningful participation. By strengthening community capacity, advancing authentic participation, and building democratic power, it might be possible to alter current patterns of health inequities. Strengthening participation by working with communities to develop the capacities needed to be effective in such processes is a key role for local, state, and national environmental agencies. PMID:22021323

Adaptations of the vestibular system to short and long-term exposures to altered gravity

NASA Astrophysics Data System (ADS)

Bruce, L. L.

2003-10-01

Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival of a given organism. The development and maintenance of vestibular connections are controlled by environmental gravitational stimulation as well as genetically controlled molecular interactions. This paper describes the effects of hypergravity on axonal growth and dendritic morphology, respectively. Two aspects of this vestibular adaptation are examined: (1) How does long-term exposure to hypergravity affect the development of vestibular axons? (2) How does short-term exposure to extremely rapid changes in gravity, such as those that occur during shuttle launch and landing, affect dendrites of the vestibulocerebellar system? To study the effects of longterm exposures to altered gravity, embryonic rats that developed in hypergravity were compared to microgravity-exposed and control rats. Examination of the vestibular projections from epithelia devoted to linear and angular acceleration revealed that the terminal fields segregate differently in rat embryos that gestated in each of the gravitational environments.To study the effects of short-term exposures to altered gravity, mice were exposed briefly to strong vestibular stimuli and the vestibulocerebellum was examined for any resulting morphological changes. My data show that these stimuli cause intense vestibular excitation of cerebellar Purkinje cells, which induce up-regulation of clathrin-mediated endocytosis and other morphological changes that are comparable to those seen in long-term depression. This system provides a basis for studying how the vestibular environment can modify cerebellar function, allowing animals to adapt to new environments.

Genetic, enzymatic and developmental alterations observed in Caiman latirostris exposed in ovo to pesticide formulations and mixtures in an experiment simulating environmental exposure.

PubMed

Poletta, Gisela L; Kleinsorge, Elisa; Paonessa, Adriana; Mudry, Marta D; Larriera, Alejandro; Siroski, Pablo A

2011-05-01

In South America, economic interests in last years have produced a constant increase in transgenic soybean cropping, with the corresponding rise in pesticide formulated products. The aim of this study was to determine the effects of pesticides formulations and mixtures on a South American caiman, Caiman latirostris, after in ovo exposure. We conducted a field-like experiment which simulates the environmental exposure that a caiman nest can receive in neighbouring croplands habitats. Experimental groups were Control group, Treatment 1: sprayed with a glyphosate herbicide formulation, and Treatment 2: sprayed with a pesticide mixture of glyphosate, endosulfan and cypermethrin formulations. Results demonstrated genotoxicity, enzymatic and metabolic alterations, as well as growth delay in caimans exposed in ovo to Treatments 1 and 2, showing a higher toxicity for the mixture. Integral evaluation through biomarkers of different biological meaning is highly informative as early indicators of contamination with pesticides and mixtures in this wildlife species. Copyright © 2010 Elsevier Inc. All rights reserved.

Can Exposure to Environmental Chemicals Increase the Risk of Diabetes Type 1 Development?

PubMed Central

Stene, Lars Christian

2015-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged. PMID:25883945

Can exposure to environmental chemicals increase the risk of diabetes type 1 development?

PubMed

Bodin, Johanna; Stene, Lars Christian; Nygaard, Unni Cecilie

2015-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Environmental exposure and altered menstrual function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keye, W.R. Jr.

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.

Arsenic Compromises Conducting Airway Epithelial Barrier Properties in Primary Mouse and Immortalized Human Cell Cultures

PubMed Central

Sherwood, Cara L.; Liguori, Andrew E.; Olsen, Colin E.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

2013-01-01

Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway. PMID:24349408

The Toxicity of Depleted Uranium

PubMed Central

Briner, Wayne

2010-01-01

Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed. PMID:20195447

Gene expression profiles in rainbow trout, Onchorynchus mykiss, exposed to a simple chemical mixture.

PubMed

Hook, Sharon E; Skillman, Ann D; Gopalan, Banu; Small, Jack A; Schultz, Irvin R

2008-03-01

Among proposed uses for microarrays in environmental toxiciology is the identification of key contributors to toxicity within a mixture. However, it remains uncertain whether the transcriptomic profiles resulting from exposure to a mixture have patterns of altered gene expression that contain identifiable contributions from each toxicant component. We exposed isogenic rainbow trout Onchorynchus mykiss, to sublethal levels of ethynylestradiol, 2,2,4,4-tetrabromodiphenyl ether, and chromium VI or to a mixture of all three toxicants Fluorescently labeled complementary DNA (cDNA) were generated and hybridized against a commercially available Salmonid array spotted with 16,000 cDNAs. Data were analyzed using analysis of variance (p<0.05) with a Benjamani-Hochberg multiple test correction (Genespring [Agilent] software package) to identify up and downregulated genes. Gene clustering patterns that can be used as "expression signatures" were determined using hierarchical cluster analysis. The gene ontology terms associated with significantly altered genes were also used to identify functional groups that were associated with toxicant exposure. Cross-ontological analytics approach was used to assign functional annotations to genes with "unknown" function. Our analysis indicates that transcriptomic profiles resulting from the mixture exposure resemble those of the individual contaminant exposures, but are not a simple additive list. However, patterns of altered genes representative of each component of the mixture are clearly discernible, and the functional classes of genes altered represent the individual components of the mixture. These findings indicate that the use of microarrays to identify transcriptomic profiles may aid in the identification of key stressors within a chemical mixture, ultimately improving environmental assessment.

Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

PubMed

Goundadkar, Basavaraj B; Katti, Pancharatna

2017-09-01

The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (P<0.05) swimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1

PubMed Central

Mitsuhashi, Takayuki; Yonemoto, Junzo; Sone, Hideko; Kosuge, Yasuhiro; Kosaki, Kenjiro; Takahashi, Takao

2010-01-01

Dioxins have been reported to exert various adverse effects, including cell-cycle dysregulation in vitro and impairment of spatial learning and memory after in utero exposure in rodents. Furthermore, children born to mothers who are exposed to dioxin analogs polychlorinated dibenzofurans or polychlorinated biphenyls have developmental impairments in cognitive functions. Here, we show that in utero exposure to dioxins in mice alters differentiation patterns of neural progenitors and leads to decreased numbers of non-GABAergic neurons and thinner deep neocortical layers. This reduction in number of non-GABAergic neurons is assumed to be caused by accumulation of cyclin-dependent kinase inhibitor p27Kip1 in nuclei of neural progenitors. Lending support to this presumption, mice lacking p27Kip1 are not susceptible to in utero dioxin exposure. These results show that environmental pollutants may affect neocortical histogenesis through alterations of functions of specific gene(s)/protein(s) (in our case, dioxins), exerting adverse effects by altering functions of p27Kip1. PMID:20805476

Epigenomics, gestational programming and risk of metabolic syndrome.

PubMed

Desai, M; Jellyman, J K; Ross, M G

2015-04-01

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.

In utero exposure to fine particulate matter results in an altered neuroimmune phenotype in adult mice.

PubMed

Kulas, Joshua A; Hettwer, Jordan V; Sohrabi, Mona; Melvin, Justine E; Manocha, Gunjan D; Puig, Kendra L; Gorr, Matthew W; Tanwar, Vineeta; McDonald, Michael P; Wold, Loren E; Combs, Colin K

2018-05-22

Environmental exposure to air pollution has been linked to a number of health problems including organ rejection, lung damage and inflammation. While the deleterious effects of air pollution in adult animals are well documented, the long-term consequences of particulate matter (PM) exposure during animal development are uncertain. In this study we tested the hypothesis that environmental exposure to PM 2.5 μm in diameter in utero promotes long term inflammation and neurodegeneration. We evaluated the behavior of PM exposed animals using several tests and observed deficits in spatial memory without robust changes in anxiety-like behavior. We then examined how this affects the brains of adult animals by examining proteins implicated in neurodegeneration, synapse formation and inflammation by western blot, ELISA and immunohistochemistry. These tests revealed significantly increased levels of COX2 protein in PM2.5 exposed animal brains in addition to changes in synaptophysin and Arg1 proteins. Exposure to PM2.5 also increased the immunoreactivity for GFAP, a marker of activated astrocytes. Cytokine concentrations in the brain and spleen were also altered by PM2.5 exposure. These findings indicate that in utero exposure to particulate matter has long term consequences which may affect the development of both the brain and the immune system in addition to promoting inflammatory change in adult animals. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex

PubMed Central

Kenet, T.; Froemke, R. C.; Schreiner, C. E.; Pessah, I. N.; Merzenich, M. M.

2007-01-01

Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams during gestation and throughout three subsequent nursing weeks. Although the hearing sensitivity and brainstem auditory responses of pups were normal, exposure resulted in the abnormal development of the primary auditory cortex (A1). A1 was irregularly shaped and marked by internal nonresponsive zones, its topographic organization was grossly abnormal or reversed in about half of the exposed pups, the balance of neuronal inhibition to excitation for A1 neurons was disturbed, and the critical period plasticity that underlies normal postnatal auditory system development was significantly altered. These findings demonstrate that developmental exposure to this class of environmental contaminant alters cortical development. It is proposed that exposure to noncoplanar PCBs may contribute to common developmental disorders, especially in populations with heritable imbalances in neurotransmitter systems that regulate the ratio of inhibition and excitation in the brain. We conclude that the health implications associated with exposure to noncoplanar PCBs in human populations merit a more careful examination. PMID:17460041

Inhalational exposure to carbonyl sulfide produces altered brainstem auditory and somatosensory-evoked potentials in Fischer 344N rats.

PubMed

Herr, David W; Graff, Jaimie E; Moser, Virginia C; Crofton, Kevin M; Little, Peter B; Morgan, Daniel L; Sills, Robert C

2007-01-01

Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131-145; Sills et al., 2004, Toxicol. Pathol. 32, 1-10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash-evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage.

Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates

PubMed Central

Singh, Sher; Li, Steven Shoei-Lung

2012-01-01

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis. PMID:22949852

Epigenetic effects of environmental chemicals bisphenol A and phthalates.

PubMed

Singh, Sher; Li, Steven Shoei-Lung

2012-01-01

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.

Long-term food-exposure of zebrafish to PCB mixtures mimicking some environmental situations induces ovary pathology and impairs reproduction ability.

PubMed

Daouk, Tarek; Larcher, Thibaut; Roupsard, François; Lyphout, Laura; Rigaud, Cyril; Ledevin, Mireille; Loizeau, Véronique; Cousin, Xavier

2011-10-01

Although the use of polychlorinated biphenyls (PCBs) has been banned for several decades, they are still present in the environment and are occasionally mechanically released from sediment or transferred through the trophic chain. Field analyses have established correlations between exposure to PCBs and alterations in fish physiology including reproductive function. Experimental exposures have been mainly performed using dioxin-like PCBs or other congeners at very high concentrations. However, these studies are often difficult to relate to real-life conditions. In the present study, we performed a life-cycle exposure using zebrafish model and mixtures representative of some environmental situations in terms of doses, composition and containing mainly non dioxin-like congeners. Exposure was performed through diet which is the main contamination route in the field. We demonstrated a bioaccumulation of PCBs in males and females as well as a maternal transfer to the eggs. Survival, growth and organ size were similar for all conditions. Several reproductive traits were altered after exposure to a PCB-contaminated diet, including a reduction in the number of fertilized eggs per spawn as well as an increase of the number of poorly fertilized spawns. This latter observation was found irrespective of the sex of contaminated fish. This is related to modifications of ovary histology revealing a decrease of maturing follicles and an increase of atretic follicles in the ovaries of females exposed to PCBs. These results indicate that exposure to PCBs mixtures mimicking some environmental situations, including mainly non dioxin-like congeners, can lead to a dramatic reduction in the number of offspring produced by a female over a lifetime. This is of great concern for wild species living under natural conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

Exposure of rats to environmental tobacco smoke during cerebellar development alters behavior and perturbs mitochondrial energetics.

PubMed

Fuller, Brian F; Cortes, Diego F; Landis, Miranda K; Yohannes, Hiyab; Griffin, Hailey E; Stafflinger, Jillian E; Bowers, M Scott; Lewis, Mark H; Fox, Michael A; Ottens, Andrew K

2012-12-01

Environmental tobacco smoke (ETS) exposure is linked to developmental deficits and disorders with known cerebellar involvement. However, direct biological effects and underlying neurochemical mechanisms remain unclear. We sought to identify and evaluate underlying neurochemical change in the rat cerebellum with ETS exposure during critical period development. We exposed rats to daily ETS (300, 100, and 0 µg/m3 total suspended particulate) from postnatal day 8 (PD8) to PD23 and then assayed the response at the behavioral, neuroproteomic, and cellular levels. Postnatal ETS exposure induced heightened locomotor response in a novel environment on par initially with amphetamine stimulation. The cerebellar mitochondrial subproteome was significantly perturbed in the ETS-exposed rats. Findings revealed a dose-dependent up-regulation of aerobic processes through the modification and increased translocation of Hk1 to the mitochondrion with corresponding heightened ATP synthase expression. ETS exposure also induced a dose-dependent increase in total Dnm1l mitochondrial fission factor; although more active membrane-bound Dnm1l was found at the lower dose. Dnm1l activation was associated with greater mitochondrial staining, particularly in the molecular layer, which was independent of stress-induced Bcl-2 family dynamics. Further, electron microscopy associated Dnm1l-mediated mitochondrial fission with increased biogenesis, rather than fragmentation. The critical postnatal period of cerebellar development is vulnerable to the effects of ETS exposure, resulting in altered behavior. The biological effect of ETS is underlain in part by a Dnm1l-mediated mitochondrial energetic response at a time of normally tight control. These findings represent a novel mechanism by which environmental exposure can impact neurodevelopment and function.

Integrating mitochondriomics in children’s environmental health

PubMed Central

Brunst, Kelly J.; Baccarelli, Andrea A.; Wright, Rosalind J.

2016-01-01

The amount of scientific research linking environmental exposures and childhood health outcomes continues to grow; yet few studies have teased out the mechanisms involved in environmentally-induced diseases. Cells can respond to environmental stressors in many ways: inducing oxidative stress/inflammation, changes in energy production and epigenetic alterations. Mitochondria, tiny organelles that each retains their own DNA, are exquisitely sensitive to environmental insults and are thought to be central players in these pathways. While it is intuitive that mitochondria play an important role in disease processes, given that every cell of our body is dependent on energy metabolism, it is less clear how environmental exposures impact mitochondrial mechanisms that may lead to enhanced risk of disease. Many of the effects of the environment are initiated in utero and integrating mitochondriomics into children’s environmental health studies is a critical priority. This review will highlight (i) the importance of exploring environmental mitochondriomics in children’s environmental health, (ii) why environmental mitochondriomics is well suited to biomarker development in this context, and (iii) how molecular and epigenetic changes in mitochondria and mitochondrial DNA (mtDNA) may reflect exposures linked to childhood health outcomes. PMID:26046650

Alterations in Energy/Redox Metabolism Induced by Mitochondrial and Environmental Toxins: A Specific Role for Glucose-6-Phosphate-Dehydrogenase and the Pentose Phosphate Pathway in Paraquat Toxicity

PubMed Central

2015-01-01

Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in energy metabolism, which are specific for distinct mitochondiral/environmental toxins, are not bystanders to energy failure but also contribute significant to cell death progression. PMID:24937102

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites.

PubMed

Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; Skinner, Michael K

2018-03-28

A variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.

Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

PubMed

Moro, Angela M; Brucker, Natália; Charão, Mariele F; Sauer, Elisa; Freitas, Fernando; Durgante, Juliano; Bubols, Guilherme; Campanharo, Sarah; Linden, Rafael; Souza, Ana P; Bonorino, Cristina; Moresco, Rafael; Pilger, Diogo; Gioda, Adriana; Farsky, Sandra; Duschl, Albert; Garcia, Solange C

2015-02-01

Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

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

EPA Science Inventory

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...

Prenatal and Infant Exposure to an Environmental Pollutant Damages Brain Architecture and Plasticity. Science Briefs

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2007

2007-01-01

"Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief reports on the study "Perinatal Exposure to a Noncoplanar Bichlorinated Biphenol Alters Tonotopy, Receptive Fields and Plasticity in the Auditory Cortex" (T. Kenet; R. C. Froemke; C. E. Schreiner; I. N. Pessah; and M. M.…

Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

PubMed Central

Schneider, Mary L.; Moore, Colleen F.; Larson, Julie A.; Barr, Christina S.; DeJesus, Onofre T.; Roberts, Andrew D.

2009-01-01

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections. PMID:19936317

Role of Autonomic Reflex Arcs in Cardiovascular Responses to Air Pollution Exposure

PubMed Central

Hazari, Mehdi S.; Farraj, Aimen K.

2016-01-01

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro-and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems. PMID:25123706

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Yueh-Hsia; Kuo, Yu-Chun; Tsai, Ming-Hsien

Exposure to environmental aryl hydrocarbon receptor (AhR) agonists, such as halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs), has great impacts on the development of various lung diseases. As emerging molecular targets for AhR agonists, cytokines may contribute to the inflammatory or immunotoxic effects of environmental AhR agonists. However, general cytokine expression may not specifically indicate environmental AhR agonist exposure. By comparing cytokine and chemokine expression profiles in human lung adenocarcinoma cell line CL5 treated with AhR agonists and the non-AhR agonist polychlorinated biphenyl (PCB) 39, we identified a target cytokine of environmental AhR agonist exposure of in the lungs.more » Thirteen cytokine and chemokine genes were altered in the AhR agonists-treated cells, but none were altered in the PCB39-treated cells. Interleukin (IL)-24 was the most highly induced gene among AhR-modulated cytokines. Cotreatment with AhR antagonist completely prevented IL-24 induction by AhR agonists in the CL5 cells. Knockdown AhR expression with short-hairpin RNA (shRNA) significantly reduced benzo[a]pyrene (BaP)-induced IL-24 mRNA levels. We further confirmed that gene transcription, but not mRNA stability, was involved in IL-24 upregulation by BaP. Particulate matter (PM) in the ambient air contains some PAHs and is reported to activate AhR. Oropharyngeal aspiration of PM significantly increased IL-24 levels in lung epithelia and in bronchoalveolar lavage fluid of mice 4 weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists. - Graphical abstract: (A) Cytokine and chemokine gene expressions were examined in CL5 cells treated with AhR and non-AhR agonists. Thirteen cytokines and chemokines genes were altered in the AhR agonist-treated cells, but not in the non-AhR agonist-treated cells. IL-24 was the most highly induced gene among the AhR-modulated cytokines. (B) Both AhR agonists and PM{sub 2.5} induced IL-24 production in the CL5 cells and macrophages. Cotreatment with an AhR antagonist (DMF) or transfections with shRNA for AhR abolished IL-24 induction by BaP in CL5 cells. Intratracheal instillation of PM activated AhR-mediated inflammatory responses and IL-24 expression in mouse lungs. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonist. - Highlights: • IL-24 is identified as a target cytokine of environmental AhR agonist exposure. • AhR agonists increased IL-24 expression in an AhR-dependent manner in lung cells. • Ambient particulate matter induces IL-24 secretion in BALF in mice. • IL-24 can be used to evaluate environmental lung diseases.« less

NOVEL METHODS FOR TARGET PROTEIN IDENTIFICATION USING IMMUNOPRECIPITATION - LC/MS/MS

EPA Science Inventory

Proteomics provides a powerful approach to screen and analyze responses to environmental exposures which induce alterations in protein expression, phosphorylation. ubiquitinylation, oxidation. and modulation of general proteome function. Post-translational modifications (PTM) of ...

Epigenetic programming alterations in alligators from environmentally contaminated lakes

PubMed Central

Guillette, Louis J.; Parrott, Benjamin B.; Nilsson, Eric; Haque, M.M.; Skinner, Michael K.

2016-01-01

Previous studies examining the reproductive health of alligators in Florida lakes indicate that a variety of developmental and health impacts can be attributed to a combination of environmental quality and exposures to environmental contaminants. The majority of these environmental contaminants have been shown to disrupt normal endocrine signaling. The potential that these environmental conditions and contaminants may influence epigenetic status and correlate to the health abnormalities was investigated in the current study. The red blood cell (RBC) (erythrocyte) in the alligator is nucleated so was used as an easily purified marker cell to investigate epigenetic programming. RBCs were collected from adult male alligators captured at three sites in Florida, each characterized by varying degrees of contamination. While Lake Woodruff (WO) has remained relatively pristine, Lake Apopka (AP) and Merritt Island (MI) convey exposures to different suites of contaminants. DNA was isolated and methylated DNA immuno-precipitation (MeDIP) was used to isolate methylated DNA that was then analyzed in a competitive hybridization using a genome-wide alligator tiling array for a MeDIP-Chip analysis. Pairwise comparisons of alligators from AP and MI to WO revealed alterations in the DNA methylome. The AP vs. WO comparison identified 85 differential DNA methylation regions (DMRs) with ⩾3 adjacent oligonucleotide tiling array probes and 15,451 DMRs with a single oligo probe analysis. The MI vs. WO comparison identified 75 DMRs with the ⩾3 oligo probe and 17,411 DMRs with the single oligo probe analysis. There was negligible overlap between the DMRs identified in AP vs. WO and MI vs. WO comparisons. In both comparisons DMRs were primarily associated with CpG deserts which are regions of low CpG density (1–2 CpG/100 bp). Although the alligator genome is not fully annotated, gene associations were identified and correlated to major gene class functional categories and pathways of endocrine relevance. Observations demonstrate that environmental quality may be associated with epigenetic programming and health status in the alligator. The epigenetic alterations may provide biomarkers to assess the environmental exposures and health impacts on these populations of alligators. PMID:27080547

A common neonicotinoid pesticide, thiamethoxam, impairs honey bee flight ability.

PubMed

Tosi, Simone; Burgio, Giovanni; Nieh, James C

2017-04-26

Pesticides can pose environmental risks, and a common neonicotinoid pesticide, thiamethoxam, decreases homing success in honey bees. Neonicotinoids can alter bee navigation, but we present the first evidence that neonicotinoid exposure alone can impair the physical ability of bees to fly. We tested the effects of acute or chronic exposure to thiamethoxam on the flight ability of foragers in flight mills. Within 1 h of consuming a single sublethal dose (1.34 ng/bee), foragers showed excitation and significantly increased flight duration (+78%) and distance (+72%). Chronic exposure significantly decreased flight duration (-54%), distance (-56%), and average velocity (-7%) after either one or two days of continuous exposure that resulted in bees ingesting field-relevant thiamethoxam doses of 1.96-2.90 ng/bee/day. These results provide the first demonstration that acute or chronic exposure to a neonicotinoid alone can significantly alter bee flight. Such exposure may impair foraging and homing, which are vital to normal colony function and ecosystem services.

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

PubMed

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.

Polycystic ovary syndrome and environmental toxins.

PubMed

Rutkowska, Aleksandra Zofia; Diamanti-Kandarakis, Evanthia

2016-09-15

Polycystic ovary syndrome (PCOS) is the most common, heterogeneous, and multifactorial endocrine disorder in premenopausal women. The pathophysiology of this endocrinopathy is still unclear; however, the heterogeneity of its features within ethnic races, geographic location, and families suggests that environment and lifestyle are of prime importance. This work is mainly focused on the possible role of the most common and studied environmental toxins for this syndrome in the pathogenesis of PCOS. Plasticizers, such as bisphenol A (BPA) or phthalates, which belong to the categories of endocrine disrupting chemicals (EDCs) and advanced glycation end products (AGEs), affect humans' health in everyday, industrialized life; therefore special attention should be paid to such exposure. Timing of exposure to EDCs is crucial for the intensity of adverse health effects. It is now evident that fetuses, infants, and/or young children are the most susceptible groups, especially in the early development periods. Prenatal exposure to EDCs that mimic endogenous hormones may contribute to the altered fetal programming and in consequence lead to PCOS and other adverse health effects, potentially transgenerationally. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. They may also interfere with metabolic alterations such as obesity, insulin resistance, and compensatory hyperinsulinemia that can exacerbate the PCOS phenotype and contribute to PCOS consequences such as type 2 diabetes and cardiovascular disease. Since wide exposure to environmental toxins and their role in the pathophysiology of PCOS are supported by extensive data derived from diverse scientific models, protective strategies and strong recommendations should be considered to reduce human exposure to protect present and future generations from their adverse health effects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Mitochondrial Dysfunction, Disruption of F-Actin Polymerization, and Transcriptomic Alterations in Zebrafish Larvae Exposed to Trichloroethylene.

PubMed

Wirbisky, Sara E; Damayanti, Nur P; Mahapatra, Cecon T; Sepúlveda, Maria S; Irudayaraj, Joseph; Freeman, Jennifer L

2016-02-15

Trichloroethylene (TCE) is primarily used as an industrial degreasing agent and has been in use since the 1940s. TCE is released into the soil, surface, and groundwater. From an environmental and regulatory standpoint, more than half of Superfund hazardous waste sites on the National Priority List are contaminated with TCE. Occupational exposure to TCE occurs primarily via inhalation, while environmental TCE exposure also occurs through ingestion of contaminated drinking water. Current literature links TCE exposure to various adverse health effects including cardiovascular toxicity. Current studies aiming to address developmental cardiovascular toxicity utilized rodent and avian models, with the majority of studies using relatively higher parts per million (mg/L) doses. In this study, to further investigate developmental cardiotoxicity of TCE, zebrafish embryos were treated with 0, 10, 100, or 500 parts per billion (ppb; μg/L) TCE during embryogenesis and/or through early larval stages. After the appropriate exposure period, angiogenesis, F-actin, and mitochondrial function were assessed. A significant dose-response decrease in angiogenesis, F-actin, and mitochondrial function was observed. To further complement this data, a transcriptomic profile of zebrafish larvae was completed to identify gene alterations associated with the 10 ppb TCE exposure. Results from the transcriptomic data revealed that embryonic TCE exposure caused significant changes in genes associated with cardiovascular disease, cancer, and organismal injury and abnormalities with a number of targets in the FAK signaling pathway. Overall, results from our study support TCE as a developmental cardiovascular toxicant, provide molecular targets and pathways for investigation in future studies, and indicate a need for continued priority for environmental regulation.

In Vivo Exposure to Inorganic Arsenic Alters Differentiation-Specific Gene Expression of Adipose-Derived Mesenchymal Stem/Stromal Cells in C57BL/6J Mouse Model

PubMed Central

Shearer, Joseph J.; Figueiredo Neto, Manoel; Umbaugh, C. Samuel; Figueiredo, Marxa L.

2017-01-01

Abstract The number of mesenchymal stem cell (MSC) therapeutic modalities has grown in recent years. Adipose-derived mesenchymal stem/stromal cells (ASCs) can be isolated and expanded relatively easily as compared with their bone-marrow counterparts, making them a particularly promising source of MSCs. And although the biological mechanisms surrounding ASCs are actively being investigated, little is known about the effects that in vivo environmental exposures might have on their ability to properly differentiate. Therefore, we hypothesized that ASCs isolated from mice exposed to inorganic arsenic (iAs) would have an altered response towards adipogenic, osteogenic, and/or chondrogenic differentiation. To test this hypothesis, C57BL/6J male mice were provided drinking water containing 0, 300, or 1000 ppb iAs. ASCs were then isolated and differentiated, which was assessed by immunocytochemistry and real-time quantitative PCR (RT-qPCR). Our results showed that total urinary arsenic equilibrated within 1 week of exposure to iAs and was maintained throughout the study. ASCs isolated from each exposure group maintained differentiation capabilities for each lineage. The magnitude of differentiation-specific gene expression, however, appeared to be concentration dependent. For osteogenesis and chondrogenesis, differentiation-specific gene expression decreased, whereas adipogenesis showed a biphasic response with an initial decrease followed by an increase in adipogenic-related gene expression following iAs exposure. These results suggest that the level in which differentiation-specific genes are induced within these stromal cells might be sensitive to environmental contaminants. These findings highlight the need to take into account potential environmental exposures prior to selecting stromal cell donors, so ASCs can achieve optimal efficiency in regenerative therapy applications. PMID:28206643

Psychotic disorder and educational achievement: a family-based analysis.

PubMed

Frissen, Aleida; Lieverse, Ritsaert; Marcelis, Machteld; Drukker, Marjan; Delespaul, Philippe

2015-10-01

Early social and cognitive alterations in psychotic disorder, associated with familial liability and environmental exposures, may contribute to lower than expected educational achievement. The aims of the present study were to investigate (1) how differences in educational level between parents and their children vary across patients, their healthy siblings, and healthy controls (effect familial liability), and across two environmental risk factors for psychotic disorder: childhood trauma and childhood urban exposure (effect environment) and (2) to what degree the association between familial liability and educational differential was moderated by the environmental exposures. Patients with a diagnosis of non-affective psychotic disorder (n = 629), 552 non-psychotic siblings and 326 healthy controls from the Netherlands and Belgium were studied. Participants reported their highest level of education and that of their parents. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire-Short Form. Urban exposure, expressed as population density, was rated across five levels. Overall, participants had a higher level of education than their parents. This difference was significantly reduced in the patient group, and the healthy siblings displayed intergenerational differences that were in between those of controls and patients. Higher levels of childhood urban exposure were also associated with a smaller intergenerational educational differential. There was no evidence for differential sensitivity to childhood trauma and childhood urbanicity across the three groups. Intergenerational difference in educational achievements is decreased in patients with psychotic disorder and to a lesser extent in siblings of patients with psychotic disorder, and across higher levels of childhood urban exposure. More research is required to better understand the dynamics between early social and cognitive alterations in those at risk in relation to progress through the educational system and to understand the interaction between urban environment and educational outcomes.

Medaka as a model for studying environmentally induced epigenetic transgenerational inheritance of phenotypes

PubMed Central

2016-01-01

Abstract Ability of environmental stressors to induce transgenerational diseases has been experimentally demonstrated in plants, worms, fish, and mammals, indicating that exposures affect not only human health but also fish and ecosystem health. Small aquarium fish have been reliable model to study genetic and epigenetic basis of development and disease. Additionally, fish can also provide better, economic opportunity to study transgenerational inheritance of adverse health and epigenetic mechanisms. Molecular mechanisms underlying germ cell development in fish are comparable to those in mammals and humans. This review will provide a short overview of long-term effects of environmental chemical contaminant exposure in various models, associated epigenetic mechanisms, and a perspective on fish as model to study environmentally induced transgenerational inheritance of altered phenotypes. PMID:29492282

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia.

PubMed

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-04-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple 'hits' are required for disease progression; an initial genetic abnormality followed by additional secondary 'hits'. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

Epigenetic Transgenerational Effects of Endocrine Disruptors on Male Reproduction

PubMed Central

Guerrero-Bosagna, Carlos M.; Skinner, Michael K.

2013-01-01

Endocrine-disrupting chemicals generally function as steroid receptor signaling antagonists or agonists that influence development to promote adult-onset disease. Exposure to the endocrine disruptors during the initiation of male reproductive tract development interferes with the normal hormonal signaling and formation of male reproductive organs. In particular, exposure to the endocrine disruptor vinclozolin promotes transgenerational transmission of adult-onset disease states such as male infertility, increased frequencies of tumors, prostate disease, kidney diseases, and immune abnormalities that develop as males age. An epigenetic change in the germ line would be involved in the transgenerational transmission of these induced phenotypes. Nevertheless, other studies have also reported transgenerational transmission of induced epigenetic changes, without altering the germ line. Here we propose a nomenclature to help clarify both cases of transgenerational epigenetic transmission. An intrinsic epigenetic transgenerational process would require a germ-line involvement, a permanent alteration in the germ cell epigenome, and only one exposure to the environmental factor. An extrinsic epigenetic transgenerational process would involve an epigenetic alteration in a somatic tissue and require exposure at each generation to maintain the transgenerational phenotype. PMID:19711250

Developmental and polyamine metabolism alterations in Rhinella arenarum embryos exposed to the organophosphate chlorpyrifos.

PubMed

Sotomayor, Verónica; Lascano, Cecilia; de D'Angelo, Ana María Pechen; Venturino, Andrés

2012-09-01

Organophosphorus pesticides (OPs) are widely applied in the Alto Valle of Río Negro and Neuquén, Argentina, due to intensive fruit growing. Amphibians are particularly sensitive to environmental pollution, and OPs may transiently accumulate in ponds and channels of the region during their reproductive season. Organophosphorus pesticide exposure may alter amphibian embryonic development and the reproductive success of autochthonous species. In the present study, embryos of the common toad Rhinella arenarum were employed to assess developmental alterations and to study polyamine metabolism, which is essential to normal growth, as a possible target underlying the effects of the OP chlorpyrifos. As the duration of chlorpyrifos exposure increased and embryonic development progressed, the median lethal concentration (LC50) values decreased, and the percentage of malformed embryos increased. Developmental arrest was also observed and several morphological alterations were recorded, such as incomplete and abnormal closure of the neural tube, dorsal curvature of the caudal fin, reduction of body size and caudal fin length, atrophy, and edema. An early decrease in ornithine decarboxylase (ODC) activity and polyamine levels was also observed in embryos exposed to chlorpyrifos. The decrease in polyamine contents in tail bud embryos might be a consequence of the reduction in ODC activity. The alteration of polyamine metabolism occurred before embryonic growth was interrupted and embryonic malformations were observed and may be useful as a biomarker in environmental studies. Copyright © 2012 SETAC.

Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: Executive Summary

PubMed Central

Woodruff, Tracey J.; Carlson, Alison; Schwartz, Jackie M.; Giudice, Linda C.

2008-01-01

The 2007 Summit on “Environmental Challenges to Reproductive Health and Fertility” convened scientists, health care professionals, community groups, political representatives and the media to hear presentations on the impact of environmental contaminants on reproductive health and fertility and to discuss opportunities to improve health through research, education, communication and policy. Environmental reproductive health focuses on exposures to environmental contaminants, particularly during critical periods of development, and their potential effects on future reproductive health, including conception, fertility, pregnancy, adolescent development and adult health. Approximately 87,000 chemical substances are registered for use in commerce in the US, with ubiquitous human exposures to environmental contaminants in air, water, food and consumer products. Exposures during critical windows of susceptibility may result in adverse effects with lifelong and even intergenerational health impacts. Effects can include impaired development and function of the reproductive tract and permanently altered gene expression, leading to metabolic and hormonal disorders, reduced fertility and fecundity and illnesses such as testicular, prostate, uterine and cervical cancers later in life. This executive summary reviews effects of pre- and post-natal exposures on male and female reproductive health and provides a series of recommendations for advancing the field in the areas of research, policy, health care and community action. PMID:18275883

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis.

PubMed

Rogers, James A; Mishra, Manoj K; Hahn, Jennifer; Greene, Catherine J; Yates, Robin M; Metz, Luanne M; Yong, V Wee

2017-05-09

Environmental and hormonal factors are implicated in dysimmunity in multiple sclerosis. We investigated whether bisphenol-A, a prominent contaminant with endocrine-disrupting capabilities, altered susceptibility in an inflammatory model of multiple sclerosis. We found that gestational, but not adult, exposure to bisphenol-A increased the development of experimental autoimmune encephalomyelitis in adulthood in male, but not female, mice when a suboptimal disease-inducing immunization was used. Gestational bisphenol-A in male mice primed macrophages in adulthood and raised granulocyte-colony stimulating factor and neutrophil counts/activity postsuboptimal immunization. Neutralizing granulocyte-colony stimulating factor blocked susceptibility to disease in bisphenol-A mice. Early life exposure to bisphenol-A may represent an environmental consideration in multiple sclerosis.

Extracellular Vesicles: How the External and Internal Environment Can Shape Cell-To-Cell Communication.

PubMed

Neven, Kristof Y; Nawrot, Tim S; Bollati, Valentina

2017-03-01

To summarize the scientific evidence regarding the effects of environmental exposures on extracellular vesicle (EV) release and their contents. As environmental exposures might influence the aging phenotype in a very strict way, we will also report the role of EVs in the biological aging process. EV research is a new and quickly developing field. With many investigations conducted so far, only a limited number of studies have explored the potential role EVs play in the response and adaptation to environmental stimuli. The investigations available to date have identified several exposures or lifestyle factors able to modify EV trafficking including air pollutants, cigarette smoke, alcohol, obesity, nutrition, physical exercise, and oxidative stress. EVs are a very promising tool, as biological fluids are easily obtainable biological media that, if successful in identifying early alterations induced by the environment and predictive of disease, would be amenable to use for potential future preventive and diagnostic applications.

Endotoxin Inhalation Alters Lung Development in Neonatal Mice

PubMed Central

Kulhankova, Katarina; George, Caroline L.S.; Kline, Joel N.; Darling, Melissa; Thorne, Peter S.

2012-01-01

Background Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. Methods We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. Results Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. Conclusions Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children. PMID:22576659

Climate change impacts on human exposures to air pollution ...

EPA Pesticide Factsheets

This is an abstract for a presentations at the Annual Conference of the International Society on Exposure Science and Environmental Epidemiology. This presentation will serve as an introduction to the symposium. As we consider the potential health impacts of a warming planet, the relationships between climate change and air pollutants become increasingly important to understand. These relationships are complex and highly variable, causing a variety of environmental impacts at local, regional and global scales. Human exposures and health impacts for air pollutants have the potential to be altered by changes in climate through multiple factors that drive population exposures to these pollutants. Research on this topic will provide both state and local governments with the tools and scientific knowledge base to undertake any necessary adaptation of the air pollution regulations and/or public health management systems in the face of climate change.

Environmentally relevant exposure to 17α-ethinylestradiol affects the telencephalic proteome of male fathead minnows

PubMed Central

Martyniuk, Christopher J.; Kroll, Kevin J.; Doperalski, Nicholas J.; Barber, David S.; Denslow, Nancy D.

2010-01-01

Estrogens are key mediators of neuronal processes in vertebrates. As such, xenoestrogens present in the environment have the potential to alter normal central nervous system (CNS) function. The objectives of the present study were 1) to identify proteins with altered expression in the male fathead minnow telencephalon as a result of low level exposure to 17α-ethinylestradiol (EE2), and 2) to better understand the underlying mechanisms of 17β-estradiol (E2) feedback in this important neuroendocrine tissue. Male fathead minnows exposed to a measured concentration of 5.4 ng EE2/L for 48 hours showed decreased plasma E2 levels of approximately 2-fold. Of 77 proteins that were quantified statistically, 14 proteins were down-regulated after EE2 exposure, including four histone proteins, ATP synthase, H+ transporting subunits, and metabolic proteins (lactate dehydrogenase B4, malate dehydrogenase 1b). Twelve proteins were significantly induced by EE2 including microtubule-associated protein tau (MAPT), astrocytic phosphoprotein, ependymin precursor, and calmodulin. MAPT showed an increase in protein abundance but a decrease in mRNA expression after EE2 exposure, suggesting there may be a negative feedback response in the telencephalon to decrease mRNA transcription with increasing MAPT protein abundance. These results demonstrate that a low, environmentally relevant exposure to EE2 can rapidly alter the abundance of proteins involved in cell differentiation and proliferation, neuron network morphology, and long term synaptic potentiation. Together, these findings provide a better understanding of the molecular responses underlying E2 feedback in the brain and demonstrate that quantitative proteomics can be successfully used in ecotoxicology to characterize affected cellular pathways and endocrine physiology. PMID:20381887

Environmentally relevant exposure to 17alpha-ethinylestradiol affects the telencephalic proteome of male fathead minnows.

PubMed

Martyniuk, Christopher J; Kroll, Kevin J; Doperalski, Nicholas J; Barber, David S; Denslow, Nancy D

2010-07-15

Estrogens are key mediators of neuronal processes in vertebrates. As such, xenoestrogens present in the environment have the potential to alter normal central nervous system (CNS) function. The objectives of the present study were (1) to identify proteins with altered abundance in the male fathead minnow telencephalon as a result of low-level exposure to 17alpha-ethinylestradiol (EE(2)), and (2) to better understand the underlying mechanisms of 17beta-estradiol (E(2)) feedback in this important neuroendocrine tissue. Male fathead minnows exposed to a measured concentration of 5.4 ng EE(2)/L for 48 h showed decreased plasma E(2) levels of approximately 2-fold. Of 77 proteins that were quantified statistically, 14 proteins were down-regulated after EE(2) exposure, including four histone proteins, ATP synthase, H+ transporting subunits, and metabolic proteins (lactate dehydrogenase B4, malate dehydrogenase 1b). Twelve proteins were significantly induced by EE(2) including microtubule-associated protein tau (Mapt), astrocytic phosphoprotein, ependymin precursor, and calmodulin. Mapt showed an increase in protein abundance but a decrease in mRNA expression after EE(2) exposure(,) suggesting there may be a negative feedback response in the telencephalon to decreased mRNA transcription with increasing Mapt protein abundance. These results demonstrate that a low, environmentally relevant exposure to EE(2) can rapidly alter the abundance of proteins involved in cell differentiation and proliferation, neuron network morphology, and long-term synaptic potentiation. Together, these findings provide a better understanding of the molecular responses underlying E(2) feedback in the brain and demonstrate that quantitative proteomics can be successfully used in ecotoxicology to characterize affected cellular pathways and endocrine physiology. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blossom, Sarah J., E-mail: blossomsarah@uams.edu; Cooney, Craig A.; Melnyk, Stepan B.

2013-06-15

Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers ofmore » oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor activity and exploratory behavior.« less

Developmental exposure to triclosan alters microbiota community structure and locomotor activity in larval zebrafish

EPA Science Inventory

Growing evidence indicates that host-associated microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals; however, current risk assessment methods do not consider interactions between microbiota and chemical toxicity. We previously reported that micro...

EE2 Changes Gene Expression in Fathead Minnow Testis

EPA Science Inventory

Environmental estrogens have been implicated in altering reproductive health of aquatic animals. Early studies of sewage treatment effluents attributed the feminization of male fish to exposure to mixtures of natural and synthetic estrogens. One of the most potent estrogens kno...

Improving the assessment of endocrine disrupting chemical (EDC) effects on puberty

EPA Science Inventory

During puberty, key developmental events occur that are critical for normal adult male and female reproductive maturation. Recent studies raised concern that exposure to environmental chemicals alter the normal progression through puberty and lead to impaired reproductive functio...

Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation.

PubMed

Zhang, Limin; Nichols, Robert G; Correll, Jared; Murray, Iain A; Tanaka, Naoki; Smith, Philip B; Hubbard, Troy D; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J; Perdew, Gary H; Patterson, Andrew D

2015-07-01

Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Six-week-old male wild-type and Ahr-/- mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism.

Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane

2013-06-15

There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore,more » B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells. • 608 different protein spots of Jurkat T cells were quantified using 2-DE-DIGE. • Pathway analysis identified Nrf2 and AhR pathway as regulated.« less

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

PubMed

Mullen, Brian R; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly; Carpenter, Ellen M

2016-06-01

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. © The Author(s) 2016.

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications.

PubMed

Cao, Yi

2015-09-01

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

Fathers Matter: Why It’s Time to Consider the Impact of Paternal Environmental Exposures on Children’s Health

PubMed Central

Braun, Joseph M.; Messerlian, Carmen; Hauser, Russ

2017-01-01

Purpose Despite accumulating evidence from experimental animal studies showing that paternal environmental exposures induce genetic and epigenetic alterations in sperm which in turn increase the risk of adverse health outcomes in offspring, there is limited epidemiological data on the effects of human paternal preconception exposures on children’s health. We summarize animal and human studies showing that paternal preconception environmental exposures influence offspring health. We discuss specific approaches and designs for human studies to investigate the health effects of paternal preconception exposures, the specific challenges these studies may face, and how we might address them. Recent Findings In animal studies, paternal preconception diet, stress, and chemical exposures have been associated with offspring health and these effects are mediated by epigenetic modifications transmitted through sperm DNA, histones, and RNA. Most epidemiological studies have examined paternal preconception occupational exposures and their effect on the risk of birth defects and childhood cancer; few have examined the effects of low-level general population exposure to environmental toxicants. While the design and execution of epidemiological studies of paternal preconception exposures face challenges, particularly with regard to selection bias and recruitment, we believe these are tractable and that preconception studies are feasible. Summary New or augmented prospective cohort studies would be the optimal method to address the critical knowledge gaps on the effect of paternal preconception exposures on prevalent childhood health outcomes. Determining if this period of life represents a window of heightened vulnerability would improve our understanding of modifiable risk factors for children’s health and wellbeing. PMID:28848695

Adverse childhood experiences and adult smoking, Nebraska, 2011.

PubMed

Yeoman, Kristin; Safranek, Thomas; Buss, Bryan; Cadwell, Betsy L; Mannino, David

2013-09-19

Smoking is a public health risk; the prevalence of smoking among adults in Nebraska is 18.4%. Studies indicate that maltreatment of children alters their brain development, possibly increasing risk for tobacco use. Previous studies have documented associations between childhood maltreatment and adult health behaviors, demonstrating the influence of adverse experiences on tobacco use. We examined prevalence and associations between adverse childhood experiences and smoking among Nebraskans. We analyzed 2011 Nebraska Behavioral Risk Factor Surveillance System (Adverse Childhood Experience module) data, defining adverse childhood experience exposures as physical, sexual, and verbal abuse (ie, direct exposures), and household dysfunction associated with mental illness, substance abuse, divorce, domestic violence, and living with persons with incarceration histories (ie, environmental exposures). We estimated prevalence of exposures, taking into account the complex survey design. We used logistic regression with predicted margins to estimate adjusted relative risk for smoking by direct or environmental exposure. Approximately 51% of Nebraskans experienced 1 or more adverse childhood events; 7% experienced 5 or more. Prevalence of environmental exposures (42%) was significantly higher than that of direct exposures (31%). Prevalence of individual exposures ranged from 6% (incarceration of a household member) to 25% (verbal abuse). Adjusted relative risks of smoking for direct and environmental exposures were 1.5 and 1.8, respectively. We present a new method of evaluating adverse childhood experience data. Prevalence of adverse childhood experiences is high among Nebraskans, and these exposures are associated with smoking. State-specific strategies to monitor adverse events among children and provide interventions might help to decrease the smoking rate in this population.

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

PubMed Central

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-01-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

Effects of environmental noise exposure on DNA methylation in the brain and metabolic health.

PubMed

Guo, Liqiong; Li, Peng-Hui; Li, Hua; Colicino, Elena; Colicino, Silvia; Wen, Yi; Zhang, Ruiping; Feng, Xiaotian; Barrow, Timothy M; Cayir, Akin; Baccarelli, Andrea A; Byun, Hyang-Min

2017-02-01

Environmental noise exposure is associated with adverse effects on human health including hearing loss, heart disease, and changes in stress-related hormone levels. Alteration in DNA methylation in response to environmental exposures is a well-known phenomenon and it is implicated in many human diseases. Understanding how environmental noise exposures affect DNA methylation patterns may help to elucidate the link between noise and adverse effects on health. In this pilot study we examined the effects of environmental noise exposure on DNA methylation of genes related to brain function and investigated whether these changes are related with metabolic health. We exposed four groups of male Wistar rats to moderate intensity noise (70-75dB with 20-4000Hz) at night for three days as short-term exposure, and for three weeks as long-term exposure. Noise exposure was limited to 45dB during the daytime. Control groups were exposed to only 45dB, day and night. We measured DNA methylation in the Bdnf, Comt, Crhr1, Mc2r, and Snca genes in tissue from four brain regions of the rats (hippocampus, frontal lobe, medulla oblongata, and inferior colliculus). Further, we measured blood pressure and body weight after long-term noise exposure. We found that environmental noise exposure is associated with gene-specific DNA methylation changes in specific regions of the brain. Changes in DNA methylation are significantly associated with changes in body weight (between Bdnf DNA methylation and Δ body weight: r=0.59, p=0.018; and between LINE-1 ORF DNA methylation and Δ body weight: =-0.80, p=0.0004). We also observed that noise exposure decreased blood pressure (p=0.038 for SBP, p=0.017 for DBP and p 0. 017 for MAP) and decreased body weight (β=-26g, p=0.008). In conclusion, environmental noise exposures can induce changes in DNA methylation in the brain, which may be associated with adverse effects upon metabolic health through modulation of response to stress-related hormones. Copyright © 2016 Elsevier Inc. All rights reserved.

Recurrence quantification analysis to characterize cyclical components of environmental elemental exposures during fetal and postnatal development

PubMed Central

Austin, Christine; Gennings, Chris; Tammimies, Kristiina; Bölte, Sven; Arora, Manish

2017-01-01

Environmental exposures to essential and toxic elements may alter health trajectories, depending on the timing, intensity, and mixture of exposures. In epidemiologic studies, these factors are typically analyzed as a function of elemental concentrations in biological matrices measured at one or more points in time. Such an approach, however, fails to account for the temporal cyclicity in the metabolism of environmental chemicals, which if perturbed may lead to adverse health outcomes. Here, we conceptualize and apply a non-linear method–recurrence quantification analysis (RQA)–to quantify cyclical components of prenatal and early postnatal exposure profiles for elements essential to normal development, including Zn, Mn, Mg, and Ca, and elements associated with deleterious health effects or narrow tolerance ranges, including Pb, As, and Cr. We found robust evidence of cyclical patterns in the metabolic profiles of nutrient elements, which we validated against randomized twin-surrogate time-series, and further found that nutrient dynamical properties differ from those of Cr, As, and Pb. Furthermore, we extended this approach to provide a novel method of quantifying dynamic interactions between two environmental exposures. To achieve this, we used cross-recurrence quantification analysis (CRQA), and found that elemental nutrient-nutrient interactions differed from those involving toxicants. These rhythmic regulatory interactions, which we characterize in two geographically distinct cohorts, have not previously been uncovered using traditional regression-based approaches, and may provide a critical unit of analysis for environmental and dietary exposures in epidemiological studies. PMID:29112980

METHODS FOR MONITORING THE EFFECTS OF ENVIRONMENTAL TOXINS ON THE VISUAL SYSTEM.

EPA Science Inventory

A high percentage of neurotoxic compounds adversely effect the visual system. Our goal is to apply the tools of vision science to problems of toxicological import, exposure-related alterations in visual physiology, psychophysical function, and ocular development. Methods can ...

Dynamic Nature of Alterations in the Endocrine System of Fathead Minnows Exposed to Prochloraz

EPA Science Inventory

The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is controlled through various feedback mechanisms, ideally maintaining dynamic homeostasis in the face of changing environmental conditions, including exposure to chemical stressors. These studies assessed the effects of t...

Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

PubMed

Miller, V M; Zhu, Y; Bucher, C; McGinnis, W; Ryan, L K; Siegel, A; Zalcman, S

2013-10-01

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Epigenetic memory in response to environmental stressors.

PubMed

Vineis, Paolo; Chatziioannou, Aristotelis; Cunliffe, Vincent T; Flanagan, James M; Hanson, Mark; Kirsch-Volders, Micheline; Kyrtopoulos, Soterios

2017-06-01

Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero , can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible ( i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades. To explain the effects of early life experiences (such as famine and exposures to other stressors) on the long-term persistence of specific patterns of epigenetic modifications, such as DNA methylation, we propose an analogy with immune memory. We propose that an epigenetic memory can be established and maintained in self-renewing stem cell compartments. We suggest that the observations on early life effects on adult diseases and the persistence of methylation changes in smokers support our hypothesis, for which a mechanistic basis, however, needs to be further clarified. We outline a new model based on methylation changes. Although these changes seem to be mainly adaptive, they are also implicated in the pathogenesis and onset of diseases, depending on individual genotypic background and types of subsequent exposures. Elucidating the relationships between the adaptive and maladaptive consequences of the epigenetic modifications that result from complex environmental exposures is a major challenge for current and future research in epigenetics.-Vineis, P., Chatziioannou, A., Cunliffe, V. T., Flanagan, J. M., Hanson, M., Kirsch-Volders, M., Kyrtopoulos, S. Epigenetic memory in response to environmental stressors. © FASEB.

Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

PubMed

Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

2016-01-01

The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

Short-Term Exposure to Coal Combustion Waste Has Little Impact on the Skin Microbiome of Adult Spring Peepers (Pseudacris crucifer)

PubMed Central

Walke, Jenifer B.; Becker, Matthew H.; Umile, Thomas P.; Burzynski, Elizabeth A.; Minbiole, Kevin P. C.; Iannetta, Anthony A.; Santiago, Celina N.; Hopkins, William A.; Belden, Lisa K.

2016-01-01

ABSTRACT Disruptions to the microbiome can impact host health as can exposure to environmental contaminants. However, few studies have addressed how environmental contaminants impact the microbiome. We explored this question for frogs that breed in wetlands contaminated with fly ash, a by-product of coal combustion that is enriched in trace elements. We found differences in the bacterial communities among a fly ash-contaminated site and several reference wetlands. We then experimentally assessed the impacts of fly ash on the skin microbiome of adult spring peepers (Pseudacris crucifer). Frogs were exposed to fly ash in the laboratory for 12 h, the duration of a typical breeding event, and the skin microbiome was assessed after 5 days (experiment 1) or after 5 and 15 days (experiment 2). We examined bacterial community structure using 16S rRNA gene amplicon sequencing and metabolite profiles using high-pressure liquid chromatography-mass spectrometry (HPLC-MS). We found little impact as the result of acute exposure to fly ash on the bacterial communities or metabolite profiles in either experiment, suggesting that the bacterial symbiont communities of adults may be relatively resistant to brief contaminant exposure. However, housing frogs in the laboratory altered bacterial community structure in the two experiments, which supports prior research suggesting that environmental source pools are important for maintaining the amphibian skin microbiome. Therefore, for contaminants like fly ash that may alter the potential source pool of symbionts, we think it may be important to explore how contaminants affect the initial assembly of the amphibian skin microbiome in larval amphibians that develop within contaminated sites. IMPORTANCE Animals are hosts to many symbiotic microorganisms, collectively called the microbiome, that play critical roles in host health. Therefore, environmental contaminants that alter the microbiome may impact hosts. Some of the most widespread contaminants, produced worldwide, are derived from the mining, storage, and combustion of coal for energy. Fly ash, for example, is a by-product of coal combustion. It contains compounds such as arsenic, selenium, cadmium, and strontium and is a recognized source of ground and surface water contamination. Here, we experimentally investigated the impacts of short-term fly ash exposure on the skin microbiome of spring peepers, one of many species of amphibian that sometimes breed in open fly ash disposal ponds. This research provides a look into the potential impacts of fly ash on an animal's microbiome and suggests important future directions for research on the effects of environmental contaminants on the microbiome. PMID:27037118

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

PubMed

Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

PubMed Central

Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development. PMID:29472946

Social Science Collaboration with Environmental Health.

PubMed

Hoover, Elizabeth; Renauld, Mia; Edelstein, Michael R; Brown, Phil

2015-11-01

Social science research has been central in documenting and analyzing community discovery of environmental exposure and consequential processes. Collaboration with environmental health science through team projects has advanced and improved our understanding of environmental health and justice. We sought to identify diverse methods and topics in which social scientists have expanded environmental health understandings at multiple levels, to examine how transdisciplinary environmental health research fosters better science, and to learn how these partnerships have been able to flourish because of the support from National Institute of Environmental Health Sciences (NIEHS). We analyzed various types of social science research to investigate how social science contributes to environmental health. We also examined NIEHS programs that foster social science. In addition, we developed a case study of a community-based participation research project in Akwesasne in order to demonstrate how social science has enhanced environmental health science. Social science has informed environmental health science through ethnographic studies of contaminated communities, analysis of spatial distribution of environmental injustice, psychological experience of contamination, social construction of risk and risk perception, and social impacts of disasters. Social science-environmental health team science has altered the way scientists traditionally explore exposure by pressing for cumulative exposure approaches and providing research data for policy applications. A transdisciplinary approach for environmental health practice has emerged that engages the social sciences to paint a full picture of the consequences of contamination so that policy makers, regulators, public health officials, and other stakeholders can better ameliorate impacts and prevent future exposure. Hoover E, Renauld M, Edelstein MR, Brown P. 2015. Social science collaboration with environmental health. Environ Health Perspect 123:1100-1106; http://dx.doi.org/10.1289/ehp.1409283.

Social Science Collaboration with Environmental Health

PubMed Central

Hoover, Elizabeth; Renauld, Mia; Edelstein, Michael R.

2015-01-01

Background Social science research has been central in documenting and analyzing community discovery of environmental exposure and consequential processes. Collaboration with environmental health science through team projects has advanced and improved our understanding of environmental health and justice. Objective We sought to identify diverse methods and topics in which social scientists have expanded environmental health understandings at multiple levels, to examine how transdisciplinary environmental health research fosters better science, and to learn how these partnerships have been able to flourish because of the support from National Institute of Environmental Health Sciences (NIEHS). Methods We analyzed various types of social science research to investigate how social science contributes to environmental health. We also examined NIEHS programs that foster social science. In addition, we developed a case study of a community-based participation research project in Akwesasne in order to demonstrate how social science has enhanced environmental health science. Results Social science has informed environmental health science through ethnographic studies of contaminated communities, analysis of spatial distribution of environmental injustice, psychological experience of contamination, social construction of risk and risk perception, and social impacts of disasters. Social science–environmental health team science has altered the way scientists traditionally explore exposure by pressing for cumulative exposure approaches and providing research data for policy applications. Conclusions A transdisciplinary approach for environmental health practice has emerged that engages the social sciences to paint a full picture of the consequences of contamination so that policy makers, regulators, public health officials, and other stakeholders can better ameliorate impacts and prevent future exposure. Citation Hoover E, Renauld M, Edelstein MR, Brown P. 2015. Social science collaboration with environmental health. Environ Health Perspect 123:1100–1106; http://dx.doi.org/10.1289/ehp.1409283 PMID:25966491

Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

PubMed

Veiga-Lopez, Almudena; Luense, Lacey J; Christenson, Lane K; Padmanabhan, Vasantha

2013-05-01

Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.

Histopathological and biochemical evidence of hepatopancreatic toxicity caused by cadmium in white shrimp, Palaemonetes argentinus.

PubMed

Chiodi Boudet, L N; Polizzi, P; Romero, M B; Robles, A; Marcovecchio, J E; Gerpe, M S

2015-03-01

Cadmium (Cd) is one of the most common pollutants in the environment and induces a range of tissue changes or damages and organ dysfunction. The histopathological effects of Cd and lipid peroxidation (LPO) on hepatopancreas of the freshwater shrimp, Palaemonetes argentinus, were studied. Shrimp were obtained from two lagoons with contrasting environmental quality, De los Padres (LP, impacted site) and Nahuel Rucá (NR, reference site), and were exposed to 3.06 and 12.24µgCdL(-1) for 3, 7, 10 and 15 days. The health status of both populations was also evaluated by histological analysis of control individuals. After exposure, shrimp were transferred to clean water for 28 days to evaluate the recuperation capacity of hepatopancreas. Control shrimp from NR exhibited a normal hepatopancreas structure; unlike control shrimp from LP which showed several alterations. These results were attributed to the different environmental quality of lagoons. The exposure to Cd resulted in several alterations in the histological structure of the hepatopancreas of both populations. The observed alterations included haemocytic and connective infiltrations in the intertubular space, erosioned microvilli, ripple of basal lamina, atrophied epithelium and necrosis, however, the latter was only observed in shrimp from LP. The exposure also caused an increase of LPO levels in both populations. P. argentinus was able to repair the hepatopancreas structure from the damage caused by Cd, evidenced by the histopathological results and LPO levels. Obtained results are indicating that the histological analysis of the hepatopancreas proved to be a highly sensitive method for evaluating water quality, in both environmental and laboratory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model

PubMed Central

Dash, M.; Eid, A.; Subaiea, G.; Chang, J.; Deeb, R.; Masoud, A.; Renehan, W.E.; Adem, A.; Zawia, N.H.

2016-01-01

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregationof the tau protein in the human brain. The best known of these illnesses is Alzheimer's disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene's ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene's expression. PMID:27293183

Assessing the safety of Pseudomonas putida introduction in the environment: an overview of ecotoxicological tests.

PubMed

de Castro, Vera Lúcia S S; Jonsson, Cláudio Martin; Silva, Célia Maria M; de Holanda Nunes Maia, Aline

2010-04-01

Risk assessment guidelines for the environmental release of microbial agents are performed in a tiered sequence which includes evaluation of exposure effects on non-target organisms. However, it becomes important to verify whether environmental risk assessment from temperate studies is applicable to tropical countries, as Brazil. Pseudomonas putida is a bacteria showing potential to be used for environmental applications as bioremediation and plant disease control. This study investigates the effects of this bacteria exposure on rodents and aquatic organisms (Daphnia similis) that are recommended to be used as non-target organism in environmental risk assessments. Also, the microbial activity in three different soils under P. putida exposure was evaluated. Rats did not show clinical alterations, although the agent was recovered 16h after the exposure in lung homogenates. The bacteria did not reduce significantly the reproduction and survival of D. similis. The soil enzymatic activities presented fluctuating values after inoculation with bacteria. The measurement of perturbations in soil biochemical characteristics is presented as an alternative way of monitoring the overall effects of the microbial agent to be introduced even in first stage (Tier I) of the risk assessment in tropical ecosystems. Copyright 2009 Elsevier Inc. All rights reserved.

Environmental and behavioral changes may influence the exposure of an Arctic apex predator to pathogens and contaminants

USGS Publications Warehouse

Atwood, Todd C.; Duncan, Colleen G.; Patyk, Kelly A.; Nol, Pauline; Rhyan, Jack; McCollum, Matthew; McKinney, Melissa A.; Ramey, Andy M.; Cerqueira-Cezar, Camila; Kwok, Oliver C H; Dubey, Jitender P; Hennager, S.G.

2017-01-01

Recent decline of sea ice habitat has coincided with increased use of land by polar bears (Ursus maritimus) from the southern Beaufort Sea (SB), which may alter the risks of exposure to pathogens and contaminants. We assayed blood samples from SB polar bears to assess prior exposure to the pathogens Brucella spp., Toxoplasma gondii, Coxiella burnetii, Francisella tularensis, and Neospora caninum, estimate concentrations of persistent organic pollutants (POPs), and evaluate risk factors associated with exposure to pathogens and POPs. We found that seroprevalence of Brucella spp. and T. gondii antibodies likely increased through time, and provide the first evidence of exposure of polar bears to C. burnetii, N. caninum, and F. tularensis. Additionally, the odds of exposure to T. gondii were greater for bears that used land than for bears that remained on the sea ice during summer and fall, while mean concentrations of the POP chlordane (ΣCHL) were lower for land-based bears. Changes in polar bear behavior brought about by climate-induced modifications to the Arctic marine ecosystem may increase exposure risk to certain pathogens and alter contaminant exposure pathways.

The biocide tributyltin reduces the accumulation of testosterone as fatty acid esters in the mud snail (Ilyanassa obsoleta).

PubMed Central

Gooding, Meredith P; Wilson, Vickie S; Folmar, Leroy C; Marcovich, Dragoslav T; LeBlanc, Gerald A

2003-01-01

Imposex, the development of male sex characteristics by female gonochoristic snails, has been documented globally and is causally associated with exposure to the ubiquitous environmental contaminant tributyltin (TBT). Elevated testosterone levels in snails also are associated with TBT, and direct exposure to testosterone has been shown to cause imposex. We discovered previously that the mud snail (Ilyanassa obsoleta)biotransforms and retains excess testosterone primarily as fatty acid esters. The purpose of this study was to determine whether TBT interferes with the esterification of testosterone, resulting in the elevated free (unesterified) testosterone levels associated with imposex. Exposure of snails to environmentally relevant concentrations of TBT (> or = 1.0 ng/L as tin) significantly increased the incidence of imposex. Total (free + esterified) testosterone levels in snails were not altered by TBT; however, free testosterone levels increased with increasing exposure concentration of TBT. TBT-exposed snails were given [14C

Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

PubMed

Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L

2016-02-01

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.

Epigenetic: a molecular link between testicular cancer and environmental exposures.

PubMed

Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A; Volle, David H

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Epigenetic: a molecular link between testicular cancer and environmental exposures

PubMed Central

Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A.; Volle, David H.

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures. PMID:23230429

Spatial and temporal age-related spectral alterations in benign human breast tissue

NASA Astrophysics Data System (ADS)

Theophilou, Georgios; Fogarty, Simon W.; Trevisan, Júlio; Strong, Rebecca J.; Heys, Kelly A.; Patel, Imran I.; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Martin, Francis L.

2016-02-01

Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.

ENVIRONMENTAL ANTIANDROGENS: LOW DOSES OF VINCLOZOLIN ALTER SEXUAL DIFFERENTIATION OF THE MALE RAT

EPA Science Inventory

In humans and rodents, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital...

Developmental Exposure to Organophosphate Flame Retardants Elicits Overt Toxicity and Alters Behavior in Zebrafish (Danio rerio)

EPA Science Inventory

Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect...

Pulmonary and Hematological Effects in Rats Following a Single Inhalation Exposure to Ce02 Nanoparticles

EPA Science Inventory

Engineered nanomaterials have unknown environmental and health implications due to their novel properties and/or by-products associated with their applications. Combustion studies have shown nanoCe-enabled fuel additives alter the physicochemical properties of diesel emissions (D...

DNA Methylation Alterations Associated with Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

EPA Science Inventory

Early-life environmental factors can influence later-life susceptibility to cancer. Epigenetic changes serve as promising biomarkers for these latent effects. Previously, we reported that short-term postnatal exposure to dichloroacetic acid (DCA), a byproduct of drinking water ch...

TOXICOGENOMICS AS A TOOL TO ASSESS EXPOSURE OF FISH TO ENVIRONMENTAL POLLUTANTS

EPA Science Inventory

Molecular biological techniques such as gene arrays and quantitative real-time PCR are becoming important tools to study alterations in normal gene expression in fish and other wildlife exposed to such pollutants as endocrine disrupting chemicals (EDCs). An important function fo...

Triclosan alterations of estuarine phytoplankton community structure.

PubMed

Pinckney, James L; Thompson, Laura; Hylton, Sarah

2017-06-15

Antimicrobial additives in pharmaceutical and personal care products are a major environmental concern due to their potential ecological impacts on aquatic ecosystems. Triclosan (TCS) has been used as an antiseptic, disinfectant, and preservative in various media. The sublethal and lethal effects of TCS on estuarine phytoplankton community composition were investigated using bioassays of natural phytoplankton communities to measure phytoplankton responses to different concentrations of TCS ranging from 1 to 200μgl -1 . The EC 50 (the concentration of an inhibitor where the growth is reduced by half) for phytoplankton groups (diatoms, chlorophytes, cryptophytes) examined in this ranged from 10.7 to 113.8μg TCS l -1 . Exposures resulted in major shifts in phytoplankton community composition at concentrations as low as 1.0μg TCS l -1 . This study demonstrates estuarine ecosystem sensitivity to TCS exposure and highlights potential alterations in phytoplankton community composition at what are typically environmental concentrations of TCS in urbanized estuaries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of biological effects of environmental pollution in Mersin Bay (Turkey, northeastern Mediterranean Sea) using Mullus barbatus and Liza ramada as target organisms.

PubMed

Yılmaz, Doruk; Kalay, Mustafa; Dönmez, Erdem; Yılmaz, Nejat

2016-01-01

The increasing emphasis on the assessment and monitoring of marine ecosystems has revealed the need to use appropriate biological indicators for these areas. Enzyme activities and histopathology are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of pollutant exposure. As part of an ecotoxicological assessment of Mersin Bay, EROD enzyme activity and histopathological response in selected organs and tissues of two species of fish, Mullus barbatus (red mullet) and Liza ramada (thinlip grey mullet), captured from area were examined. Pollutant (Organochlorines (OC), alkylphenols (APs) and BPA) levels and biomarker responses in tissue samples were evaluated together for their potential to alter the metabolism and cellular aspects in liver and gonad. Elevated induction of EROD activity and histopathological alterations in contaminated samples from Mersin Bay was observed compared to reference site indicating the exposure to potential pollutants. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

DTIC Science & Technology

2016-01-13

Institute for Science and Engineering, Oak Ridge, TN 37831, United States bUnited States Army Center for Environmental Health Research (USACEHR...online 13 January 2016 Keywords: Chlorpyrifos Cholinesterase inhibition Gene expression Microarray miRNA Organophosphorus pesticide A B S T R A C T...Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not

Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

PubMed

Swaminathan, Ashwin; Lucas, Robyn M; Harley, David; McMichael, Anthony J

2014-11-11

The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations-particularly for children-to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bardullas, U.; Limon-Pacheco, J.H.; Giordano, M.

2009-09-01

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,more » 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.« less

Epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes.

PubMed

Khan, Fazlullah; Momtaz, Saeideh; Niaz, Kamal; Hassan, Fatima Ismail; Abdollahi, Mohammad

2017-09-01

Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance. This article reviewed epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes. Electronic databases such as PubMed, Scopus and Google scholar were searched for published literature from 1980 to 2017. Searched MESH terms were "Arsenic", "Epigenetic mechanism", "DNA methylation", "Histone modifications" and "Diabetes". There are various factors involved in the pathogenesis of T2DM but it is assumed that arsenic consumption causes the epigenetic alterations both at the gene-specific level and generalized genome level. The research indicates that exposure from low to moderate concentrations of iAs is linked with the epigenetic effects. In addition, it is evident that, arsenic can change the components of the epigenome and hence induces diabetes through epigenetic mechanisms, such as alterations in glucose transport and/or metabolism and insulin expression/secretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2007-08-15

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

Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice.

PubMed

Wei, Haiyan; Zhang, Juan; Tan, Kehong; Sun, Rongli; Yin, Lihong; Pu, Yuepu

2015-11-12

Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin(-) cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin(-)c-Kit⁺ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs.

Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice

PubMed Central

Wei, Haiyan; Zhang, Juan; Tan, Kehong; Sun, Rongli; Yin, Lihong; Pu, Yuepu

2015-01-01

Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin− cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin−c-Kit+ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs. PMID:26569237

Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling

PubMed Central

Jiménez-Chillarón, Josep C; Nijland, Mark J; Ascensão, António A; Sardão, Vilma A; Magalhães, José; Hitchler, Michael J; Domann, Frederick E; Oliveira, Paulo J

2015-01-01

Epigenetics, or regulation of gene expression independent of DNA sequence, is the missing link between genotype and phenotype. Epigenetic memory, mediated by histone and DNA modifications, is controlled by a set of specialized enzymes, metabolite availability, and signaling pathways. A mostly unstudied subject is how sub-toxic exposure to several xenobiotics during specific developmental stages can alter the epigenome and contribute to the development of disease phenotypes later in life. Furthermore, it has been shown that exposure to low-dose xenobiotics can also result in further epigenetic remodeling in the germ line and contribute to increase disease risk in the next generation (multigenerational and transgenerational effects). We here offer a perspective on current but still incomplete knowledge of xenobiotic-induced epigenetic alterations, and their possible transgenerational transmission. We also propose several molecular mechanisms by which the epigenetic landscape may be altered by environmental xenobiotics and hypothesize how diet and physical activity may counteract epigenetic alterations. PMID:25774863

SOCIAL PLAY BEHAVIOR IS ALTERED IN THE RAT BY PERINATAL EXPOSURE TO ANDROGENS AND THE ENVIRONMENTAL ANTIANDROGEN, VINCLOZOLIN

EPA Science Inventory

During mammalian sexual differentiation, the androgens, testosterone and dihydrotestosterone are critical for the organization of the male phenotype. In rats, play behavior is sexually dimorphic. Administration of exogenous androgens during the perinatal period results in masculi...

THYROID STATUS IN JUVENILE ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS) FROM CONTAMINATED AND REFERENCE SITES ON LAKE OKEECHOBEE, FLORIDA, USA

EPA Science Inventory

Exposure to environmental contaminants has been shown to alter normal thyroid function in various wildlife species, including the American alligator (Alligator mississippiensis). Abnormalities in circulating levels of the thyroid hormone thyroxine (T4) have been reported in juven...

PCB126 modulates fecal microbial fermentation of the dietary fiber inulin

USDA-ARS?s Scientific Manuscript database

Exposure to environmental pollutants can alter gut microbial populations. Short-chain fatty acids (SCFAs), produced from gut microbial fermentation of dietary fibers such as inulin, exert numerous effects on host energy metabolism. SCFAs are also linked to health promoting effects, including a red...

VALUING REDUCTIONS IN ENVIRONMENTAL SOURCES OF INFERTILITY RISK USING THE EFFICIENT HOUSEHOLD FRAMEWORK

EPA Science Inventory

There is an increasing body evidence suggesting that a broad range of pollutants have the potential to alter human endocrine systems. One disturbing consequence of exposures to these endocrine disruptors is that they may significantly increase the incidence of infertility in exp...

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

PubMed

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

2017-04-24

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.

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

PubMed Central

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

Do environmental factors affect male fathead minnow (Pimephales promelas) response to estrone? Part 1. Dissolved oxygen and sodium chloride.

PubMed

Feifarek, D J; Shappell, N W; Schoenfuss, H L

2018-01-01

Laboratory exposures indicate that estrogens and their mimics can cause endocrine disruption in male fishes, yet while studies of resident fish populations in estrogen-polluted waters support these findings, biomarker expression associated with field versus laboratory exposure to estrogenic endocrine disruptors (EDs) often differ dramatically. Two of the environmental parameters often found to vary in dynamic aquatic ecosystems were chosen (dissolved oxygen [DO] and sodium chloride concentrations) to assess their potential impact on ED exposure. In separate experiments, male fathead minnows (Pimephales promelas) were exposed to estrone (E1) a natural ED, under either two concentrations of DO, or two concentrations of sodium chloride, in a laboratory flow-through system. Morphological and hematological parameters were assessed. While vitellogenin concentrations were elevated with exposure to estrone (29 to 390ng/L), the effect on other indices were variable. Estrone exposure altered SSC, blood glucose, hematocrit, and hepatic and gonado-somatic index in 1 of 4 experiments, while it decreased body condition factor in 3 of 4 experiments. At the concentrations tested, no main effect differences (P<0.05) were found associated with DO or sodium chloride treatments, except in one experiment low DO resulted in a decrease in secondary sex characteristic score (SSC). The combination of DO or sodium chloride and E1 altered blood glucose in one experiment each. These results indicate the variability of fathead minnow response to estrone, even within the confines of controlled laboratory conditions. Published by Elsevier B.V.

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

PubMed

Philbrook, Nicola A; Winn, Louise M

2015-11-15

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessment of energetic costs of AhR activation by β-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nault, Rance, E-mail: naultran@msu.edu; Abdul-Fattah, Hiba; Mironov, Gleb G.

2013-08-15

Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist β-naphthoflavone (βNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesismore » rates, Na{sup +}/K{sup +}-ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1 μM βNF for 48 h did not alter hepatocyte AEC, protein synthesis, or Na{sup +}/K{sup +}-ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies. - Highlights: • Energetic costs of AhR activation by βNF was examined in rainbow trout hepatocytes. • Metabolic flux analysis was performed on a fish cell preparation for the first time. • Exposure to βNF led to sparing of glycogen reserves and altered enzyme activities. • Adenylate energy charge was maintained despite temporal changes in metabolism.« less

Generational comparisons (F1 versus F3) of vinclozolin induced epigenetic transgenerational inheritance of sperm differential DNA methylation regions (epimutations) using MeDIP-Seq.

PubMed

Beck, Daniel; Sadler-Riggleman, Ingrid; Skinner, Michael K

2017-07-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g. sperm). These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F3 generation (great-grand-offspring) animals. The current study was designed to investigate the actions of direct fetal exposure on the F1 generation rat sperm DMRs compared to the F3 transgenerational sperm DMRs. A protocol involving methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (Seq) was used in the current study. Bioinformatics analysis of the MeDIP-Seq data was developed and several different variations in the bioinformatic analysis were evaluated. Observations indicate needs to be considered. Interestingly, the F1 generation DMRs were found to be fewer in number and for the most part distinct from the F3 generation epimutations. Observations suggest the direct exposure induced F1 generation sperm DMRs appear to promote in subsequent generations alterations in the germ cell developmental programming that leads to the distinct epimutations in the F3 generation. This may help explain the differences in disease and phenotypes between the direct exposure F1 generation and transgenerational F3 generation. Observations demonstrate a distinction between the direct exposure versus transgenerational epigenetic programming induced by environmental exposures and provide insights into the molecular mechanisms involved in the epigenetic transgenerational inheritance phenomenon.

Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice.

PubMed

Zhang, Jun; Wang, Yan; Fu, Lin; Feng, Yu-Jie; Ji, Yan-Li; Wang, Hua; Xu, De-Xiang

2018-07-01

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl 2 (10 and 100 mg l -1 ) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd-100 mg l -1 group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd-1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd-treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd-treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study. Copyright © 2018 John Wiley & Sons, Ltd.

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

DOE PAGES

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.; ...

2017-08-09

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 in this paper, 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 quantifymore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.

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 in this paper, 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 quantifymore » 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.« less

Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

PubMed Central

Heindel, Jerrold J.; Bucher, John R.; Gallo, Michael A.

2012-01-01

Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research recommendations. This review also serves as an introduction to an upcoming series of articles that review the literature regarding specific exposures and outcomes in more detail. PMID:22296744

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, Miranda L.; Brundage, Kathleen M.; Schafer, Rosana

2010-01-15

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/beta-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/beta-catenin pathways. Pregnant C57Bl/6more » 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{sup +} cells and a subpopulation of double-negative cells (DN; CD4{sup -}CD8{sup -}), DN4 (CD44{sup -}CD25{sup -}). Shh and Wnt/beta-catenin signaling were both decreased in the thymus. Target genes of Shh (Patched1 and Gli1) and Wnt/beta-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.« less

Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.

PubMed

Bruner-Tran, Kaylon L; Gnecco, Juan; Ding, Tianbing; Glore, Dana R; Pensabene, Virginia; Osteen, Kevin G

2017-03-01

Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new "Organ-on-Chip" models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Exposure to the Environmental Endocrine Disruptor TCDD and Human Reproductive Dysfunction: Translating Lessons from Murine Models

PubMed Central

Bruner-Tran, Kaylon L.; Gnecco, Juan; Ding, Tianbing; Glore, Dana R.; Pensabene, Virginia; Osteen, Kevin G.

2016-01-01

Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new “Organ-on-Chip” models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease. PMID:27423904

Developmental Origins of Health and Disease: Environmental Exposures

PubMed Central

Swanson, James M.; Entringer, Sonja; Buss, Claudia; Wadhwa, Pathik D.

2010-01-01

The developmental origins of health and disease (DOHaD) approach has evolved over the past 20 years, and the current hypothesis proposes that fetal adaptations to intrauterine and maternal conditions during development shape structure and function of organs. Here we present a review of some environmental exposures that may trigger fetal maladaptations in these processes, including three examples: exposures to tobacco smoke, antidepressant medication, and folic acid deficits in the food supply. We provide a selected review of current research on the effects of each of these exposures on fetal development and birth outcomes, and use the DOHaD approach to suggest how these exposures may alter long-term outcomes. In the interpretation of this literature, we review the evidence of gene–environment interactions based on evaluation of biological pathways and evidence that some exposures to the fetus may be moderated by maternal and fetal genotypes. Finally, we use the design of the National Children’s Study (now in progress) to propose how the DOHaD approach could be used to address questions that have emerged in this area that are relevant to reproductive medicine and subsequent health outcomes. PMID:19711249

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus.

PubMed

Morsi, Amr; DeFranco, Donald; Witchel, Selma

2018-06-06

Glucocorticoids (GCs), cortisol in humans, influence multiple essential maturational events during gestation. In the human fetus, fetal hypothalamic-pituitary-adrenal (HPA) axis function, fetal adrenal steroidogenesis, placental 11β- hydroxysteroid dehydrogenase type 2 activity, maternal cortisol concentrations, and environmental factors impact fetal cortisol exposure. The beneficial effects of synthetic glucocorticoids (sGCs), such as dexamethasone and betamethasone, on fetal lung maturation have significantly shifted the management of preterm labor and threatened preterm birth. Accumulating evidence suggests that exposure to sGCs in utero at critical developmental stages can alter the function of organ systems and that these effects may have sequelae that extend into adult life. Maternal stress and environmental influences may also impact fetal GC exposure. This article explores the vulnerability of the fetal HPA axis to endogenous GCs and exogenous sGCs. © 2018 S. Karger AG, Basel.

ALTERED GENE EXPRESSION AND DEVELOPMENT OF POTENTIAL BIOMARKERS IN MEDAKA (ORYZIAS LATIPES) BRAIN, LIVER AND TESTIS FOLLOWING EXPOSURE TO FIBRATE PHARMACEUTICALS

EPA Science Inventory

To help address the consequences of increasing levels of environmental contaminants and to identify potentially novel markers of toxicity, we examined gene expression profiles from medaka (Oryzias latipes) exposed to a prototypical fibrate pharmaceutical. Changes in gene express...

Water deficit severity during berry development alters onset of dormancy transitions in wine grape cultivar Malbec

USDA-ARS?s Scientific Manuscript database

Dormancy is a survival strategy for withstanding exposure to adverse environmental conditions. Grapevines (Vitis vinifera L.) are often exposed to water deficits during the growing season and freezing temperatures during winter, yet the influence of water stress on dormancy has received little resea...

Exposure to synthetic greywater inhibits amoebae encystation and alters expression of Legionella pneumophila virulence genes

EPA Science Inventory

Water conservation efforts have focused on greywater (GW) usage, especially for applications that do not require potable water quality. However, there is a need to better understand environmental pathogens and their free-living amoebae (FLA) hosts within GW. Using synthetic gre...

Transcriptomic changes in zebrafish embryos and larvae following benzo[a]pyrene exposure

USDA-ARS?s Scientific Manuscript database

Benzo[a]pyrene (BaP) is an environmentally relevant carcinogenic and endocrine disrupting compound that causes immediate, long-term, and multigenerational health deficits in mammals and fish. Previously, we found that BaP alters DNA methylation patterns in developing zebrafish, which may affect gene...

Dynamic Nature of Alterations in the Endocrine System of Fathead Minnows Exposed to the Fungicide Prochloraz, Presentation

EPA Science Inventory

The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is controlled through various feedback mechanisms that ideally serve to maintain a dynamic homeostasis of the system in the face of changing environmental conditions, including exposure to chemical stressors. In these stud...

ELEVATED LEVELS OF INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECT MCF-7 CELLS FROM ARSENITE TOXICITY

EPA Science Inventory

Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear whether HSP induction alters the damaging effects of environmental chemical...

In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

PubMed Central

Sirenko, Oksana; Grimm, Fabian A.; Ryan, Kristen R.; Iwata, Yasuhiro; Chiu, Weihsueh A.; Parham, Frederick; Wignall, Jessica A.; Anson, Blake; Cromwell, Evan F.; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R.

2017-01-01

An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 hrs and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca2+ flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of tested chemicals exhibited effects on cardiomyocyte rhythm after 30 min of exposure. After 24 hours, the effects on cell rhythm without cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes were visualized using Toxicological Prioritization Index (ToxPi) and showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential to alter cardiomyocyte function at high exposures, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. PMID:28259702

In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model.

PubMed

Sirenko, Oksana; Grimm, Fabian A; Ryan, Kristen R; Iwata, Yasuhiro; Chiu, Weihsueh A; Parham, Frederick; Wignall, Jessica A; Anson, Blake; Cromwell, Evan F; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R

2017-05-01

An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30min or 24h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca 2+ flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30min of exposure. In contrast, after 24h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. Copyright © 2017. Published by Elsevier Inc.

Subclinical cytomegalovirus infection associates with altered host immunity, gut microbiota and vaccine responses.

PubMed

Santos Rocha, Clarissa; Hirao, Lauren A; Weber, Mariana G; Méndez-Lagares, Gema; Chang, W L William; Jiang, Guochun; Deere, Jesse D; Sparger, Ellen E; Roberts, Jeffrey; Barry, Peter A; Hartigan-O'Connor, Dennis J; Dandekar, Satya

2018-04-18

Subclinical viral infections (SVI) including cytomegalovirus (CMV) are highly prevalent in humans, resulting in life-long persistence. However, the impact of SVI on the interplay between the host immunity and gut microbiota in the context of environmental exposures is not well defined. We utilized the preclinical nonhuman primate (NHP) model consisting of SVI-free (SPF) rhesus macaques and compared them to the animals with SVI (non-SPF) acquired through natural exposure and investigated the impact of SVI on immune cell distribution and function as well as on gut microbiota. These changes were examined in animals housed in the outdoor environment as compared to the controlled indoor environment. We report that SVI are associated with altered immune cell subsets and gut microbiota composition in animals housed in the outdoor environment. Non-SPF animals harbored a higher proportion of potential butyrate-producing Firmicutes and higher numbers of lymphocytes, effector T cells and cytokine-producing T cells. Surprisingly, these differences diminished following their transfer to the controlled indoor environment, suggesting that non-SPFs had increased responsiveness to environmental exposures. An experimental infection of indoor SPF animals with CMV resulted in an increased abundance of butyrate-producing bacteria, validating that CMV enhanced colonization of butyrate-producing commensals. Finally, non-SPF animals displayed lower antibody responses to influenza vaccination as compared to SPF animals. Our data show that subclinical CMV infection heightens host immunity and gut microbiota changes in response to environmental exposures. This may contribute to the heterogeneity in host immune response to vaccines and environmental stimuli at the population level. IMPORTANCE Humans harbor several latent viruses that modulate host immunity and commensal microbiota, thus introducing heterogeneity in their responses to pathogens, vaccines and environmental exposures. Most of our understanding of the effect of CMV on the immune system is based on studies of children acquiring CMV or of immune-compromised humans with acute or reactivated CMV infection or in ageing individuals. The experimental mouse models are genetically inbred and are completely adapted to the indoor laboratory environment. In contrast, nonhuman primates are genetically outbred and are raised in the outdoor environment. Our study is the first to report the impact of long-term subclinical CMV infection on host immunity and gut microbiota, which is evident only in the outdoor environment but not in the indoor environment. The significance of this study is in highlighting the impact of SVI on enhancing host immune susceptibility to environmental exposures and immune heterogeneity. Copyright © 2018 American Society for Microbiology.

Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress

PubMed Central

Papale, Ligia A.; Li, Sisi; Madrid, Andy; Zhang, Qi; Chen, Li; Chopra, Pankaj; Jin, Peng; Keleş, Sündüz; Alisch, Reid S.

2016-01-01

Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently, we reported a genome-wide disruption of hippocampal 5hmC in male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined the genome-wide profile of hippocampal 5hmC in female mice following exposure to acute stress and identified 363 differentially hydroxymethylated regions (DhMRs) linked to known (e.g., Nr3c1 and Ntrk2) and potentially novel genes associated with stress response and psychiatric disorders. Integration of hippocampal expression data from the same female mice found stress-related hydroxymethylation correlated to altered transcript levels. Finally, characterization of stress-induced sex-specific 5hmC profiles in the hippocampus revealed 778 sex-specific acute stress-induced DhMRs some of which were correlated to altered transcript levels that produce sex-specific isoforms in response to stress. Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex. PMID:27576189

Environmental signaling: from environmental estrogens to endocrine-disrupting chemicals and beyond.

PubMed

McLachlan, J A

2016-07-01

The landmark report (Herbst et al. 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed that DES was the carcinogen and exposure to DES caused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero. DES was also being used in agriculture and we discovered, at the first meeting on Estrogens in the Environment in 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated how DES and other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At the Wingspread Conference on the Human-Wildlife Connection in 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals alter cell differentiation. Since 2010, research has shown that trauma and other behavioral inputs can function as 'environmental signals,' can be encoded in gene regulation networks in a variety of cells and organs, and can be passed on to subsequent generations. So now we come full circle: environmental chemicals mimic hormones or other metabolic signaling molecules and now behavioral experience can be transduced into chemical signals that also modify gene expression. © 2016 American Society of Andrology and European Academy of Andrology.

Environmental perception and epigenetic memory: mechanistic insight through FLC

PubMed Central

Berry, Scott; Dean, Caroline

2015-01-01

Chromatin plays a central role in orchestrating gene regulation at the transcriptional level. However, our understanding of how chromatin states are altered in response to environmental and developmental cues, and then maintained epigenetically over many cell divisions, remains poor. The floral repressor gene FLOWERING LOCUS C (FLC) in Arabidopsis thaliana is a useful system to address these questions. FLC is transcriptionally repressed during exposure to cold temperatures, allowing studies of how environmental conditions alter expression states at the chromatin level. FLC repression is also epigenetically maintained during subsequent development in warm conditions, so that exposure to cold may be remembered. This memory depends on molecular complexes that are highly conserved among eukaryotes, making FLC not only interesting as a paradigm for understanding biological decision-making in plants, but also an important system for elucidating chromatin-based gene regulation more generally. In this review, we summarize our understanding of how cold temperature induces a switch in the FLC chromatin state, and how this state is epigenetically remembered. We also discuss how the epigenetic state of FLC is reprogrammed in the seed to ensure a requirement for cold exposure in the next generation. Significance Statement FLOWERING LOCUS C (FLC) regulation provides a paradigm for understanding how chromatin can be modulated to determine gene expression in a developmental context. This review describes our current mechanistic understanding of how FLC expression is genetically specified and epigenetically regulated throughout the plant life cycle, and how this determines plant life-history strategy. PMID:25929799

Epigenetics mediate environment : gene effects on occupational sensitization.

PubMed

Pacheco, Karin A

2012-04-01

Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.

Fetal programming and environmental exposures ...

EPA Pesticide Factsheets

Fetal programming is an enormously complex process that relies on numerous environmental inputs from uterine tissue, the placenta, the maternal blood supply, and other sources. Recent evidence has made clear that the process is not based entirely on genetics, but rather on a delicate series of interactions between genes and the environment. It is likely that epigenctic (“above the genome”) changes are responsible for modifying gene expression in the developing fetus, and these modifications can have long-lasting health impacts. Determining which epigenetic regulators are most vital in embryonic development will improve pregnancy outcomes and our ability to treat and prevent disorders that emerge later in life. “Fetal Programming and Environmental Exposures: Implications for Prenatal Care and Preterm Birth’ began with a keynote address by Frederick vom Saal, who explained that low-level exposure to endocrine disrupting chemicals (EDCs) perturbs hormone systems in utero and can have negative effects on fetal development. vom Saal presented data on the LOC bisphenol A (BPA), an estrogen-mimicking compound found in many plastics. He suggested that low-dose exposure to LOCs can alter the development process and enhance chances of acquiring adult diseases, such as breastcancer, diabetes, and even developmental disorders such as attention deficit disorder (ADHD).’ Fetal programming is an enormously complex process that relies on numerous environmental inputs

Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.

PubMed

Garza-Lombó, Carla; Posadas, Yanahi; Quintanar, Liliana; Gonsebatt, María E; Franco, Rodrigo

2018-06-20

Essential metals such as copper, iron, manganese, and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our life span, humans are also exposed to xenobiotic metals from natural and anthropogenic sources, including aluminum, arsenic, cadmium, lead, and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals are linked to several neurological disorders, including neurodegeneration and neurodevelopmental alterations. Recent Advances: The redox activity of essential metals is key for neuronal homeostasis and brain function. Alterations in redox homeostasis and signaling are central to the pathological consequences of dysfunctional metal ion homeostasis and increased exposure to xenobiotic metals. Both redox-active and redox-inactive metals trigger oxidative stress and damage in the central nervous system, and the exact mechanisms involved are starting to become delineated. In this review, we aim to appraise the role of essential metals in determining the redox balance in the brain and the mechanisms by which alterations in the homeostasis of essential metals and exposure to xenobiotic metals disturb the cellular redox balance and signaling. We focus on recent literature regarding their transport, metabolism, and mechanisms of toxicity in neural systems. Delineating the specific mechanisms by which metals alter redox homeostasis is key to understand the pathological processes that convey chronic neuronal dysfunction in neurodegenerative and neurodevelopmental disorders. Antioxid. Redox Signal. 28, 1669-1703.

Pulmonary changes on HRCT scans in nonsmoking females with COPD due to wood smoke exposure *

PubMed Central

Moreira, Maria Auxiliadora Carmo; Barbosa, Maria Alves; de Queiroz, Maria Conceição de Castro Antonelli Monteiro; Teixeira, Kim Ir Sen Santos; Torres, Pedro Paulo Teixeira e Silva; de Santana, Pedro José; Montadon, Marcelo Eustáquio; Jardim, José Roberto

2013-01-01

OBJECTIVE: To identify and characterize alterations seen on HRCT scans in nonsmoking females with COPD due to wood smoke exposure. METHODS: We evaluated 42 nonsmoking females diagnosed with wood smoke-related COPD and 31 nonsmoking controls with no history of wood smoke exposure or pulmonary disease. The participants completed a questionnaire regarding demographic data, symptoms, and environmental exposure. All of the participants underwent spirometry and HRCT of the chest. The COPD and control groups were adjusted for age (23 patients each). RESULTS: Most of the patients in the study group were diagnosed with mild to moderate COPD (83.3%). The most common findings on HRCT scans in the COPD group were bronchial wall thickening, bronchiectasis, mosaic perfusion pattern, parenchymal bands, tree-in-bud pattern, and laminar atelectasis (p < 0.001 vs. the control group for all). The alterations were generally mild and not extensive. There was a positive association between bronchial wall thickening and hour-years of wood smoke exposure. Centrilobular emphysema was uncommon, and its occurrence did not differ between the groups (p = 0.232). CONCLUSIONS: Wood smoke exposure causes predominantly bronchial changes, which can be detected by HRCT, even in patients with mild COPD. PMID:23670500

Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures.

PubMed

Nikodemova, Maria; Yee, Jeremiah; Carney, Patrick R; Bradfield, Christopher A; Malecki, Kristen Mc

2018-04-01

Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures. Overall study goals were to investigate whole blood gene expression in smokers and non-smokers to examine associations between cigarette smoke and changes in gene expression by obesity status and test for effect modification. Relative fold-change in mRNA expression levels of 84 genes were analyzed using a Toxicity and Stress PCR array among 50 21-54 year old adults. Data on smoking status was confirmed using urinary cotinine levels. Adjusted models included age, gender, white blood cell count and body-mass index. Models comparing gene expression of smokers vs. non-smokers identified six differentially expressed genes associated with smoking after adjustments for covariates. Obesity was associated with 29 genes differentially expressed compared to non-obese. We also identified 9 genes with significant smoking/obesity interactions influencing mRNA levels in adjusted models comparing expression between smokers vs non-smokers for four DNA damage related genes (GADD45A, DDB2, RAD51 and P53), two oxidative stress genes (FTH1, TXN), two hypoxia response genes (BN1P3lL, ARNT), and one gene associated with unfolded protein response (ATF6B). Findings suggest that obesity alters human sensitivity to smoke exposures through several biological pathways by modifying gene expression. Additional studies are needed to fully understand the clinical impact of these effects, but risk assessments should consider underlying phenotypes, such as obesity, that may modulate sensitivity of vulnerable populations to environmental exposures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Differential behavioural responses to venlafaxine exposure route, warming and acidification in juvenile fish (Argyrosomus regius).

PubMed

Maulvault, Ana Luísa; Santos, Lúcia H M L M; Paula, José Ricardo; Camacho, Carolina; Pissarra, Vasco; Fogaça, Fabiola; Barbosa, Vera; Alves, Ricardo; Ferreira, Pedro Pousão; Barceló, Damià; Rodriguez-Mozaz, Sara; Marques, António; Diniz, Mário; Rosa, Rui

2018-09-01

Antidepressants, such as venlafaxine (VFX), which are considered emerging environmental pollutants, are increasingly more present in the marine environment, and recent evidence suggest that they might have adverse effects on fish behaviour. Furthermore, altered environmental conditions associated to climate change (e.g. warming and acidification) can also have a determinant role on fish behaviour, fitness and survival. Yet, the underlying interactions between these environmental stressors (pharmaceuticals exposure and climate change) are still far from being fully understood. The aim of this study was to assess behavioural responses (in juvenile meagre (Argyrosomus regius) exposed to VFX via water ([VFX] ~20μgL -1 ) and via dietary sources ([VFX] ~160μgkg -1 dry weight), as well as to increased temperature (ΔT°C=+5°C) and high CO 2 levels (ΔpCO 2 ~1000μatm; equivalent to ΔpH=-0.4units). Overall, VFX bioaccumulation in fish plasma was enhanced under the combination of warming and acidification. VFX triggered fish exploration, whereas fish activity and shoal cohesion were reduced. Acidification alone decreased fish exploration and shoal cohesion, and reversed fish preference to turn leftwards compared to control conditions. Such alterations were further enhanced by VFX exposure. The combination of warming and acidification also reduced shoal cohesion and loss of lateralization, regardless of VFX exposure. The distinct behaviour observed when VFX contamination, acidification and warming acted alone or in combination highlighted the need to consider the likely interactive effects of seawater warming and acidification in future research regarding the toxicological aspects of chemical contaminants. Copyright © 2018. Published by Elsevier B.V.

Environmental triggers in IBD: a review of progress and evidence.

PubMed

Ananthakrishnan, Ashwin N; Bernstein, Charles N; Iliopoulos, Dimitrios; Macpherson, Andrew; Neurath, Markus F; Ali, Raja A Raja; Vavricka, Stephan R; Fiocchi, Claudio

2018-01-01

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

Morpho-anatomical and growth alterations induced by arsenic in Cajanus cajan (L.) DC (Fabaceae).

PubMed

Pita-Barbosa, Alice; Gonçalves, Elton Carvalho; Azevedo, Aristéa Alves

2015-08-01

Arsenic (As) is a toxic element to most organisms. Studies investigating anatomic alterations due to As exposure in plants are scarce but of utmost importance to the establishment of environmental biomonitoring techniques. So, this study aimed to investigate the effects of As on the development and initial root growth in Cajanus cajan (Fabaceae), characterize and quantify the possible damages, evaluate genotoxic effects, and identify structural markers to be used in environmental bioindication. Plants were exposed hydroponically to 0.5, 1.0, 1.5, and 2.0 mg As L(-1), as sodium arsenate. Growth parameters were measured, and in the end of the exposure, root samples were analyzed for qualitative and quantitative anatomical alterations. Arsenic genotoxicity was evaluated through analysis of the mitotic index in the root apex. Compared to the control, As-treated seedlings showed an altered architecture, with significantly decreased root length (due to the lower mitotic index in the apical meristem and reduced elongation of parenchyma cells) with darkened color, and abnormal development of the root cap. A significant increase in vascular cylinder/root diameter ratio was also detected, due to the reduction of the cellular spaces in the cortex. The secondary xylem vessel elements were reduced in diameter and had sinuous walls. The severest damage was visible in the ramification zone, where uncommon division planes of phellogen and cambium cells and disintegration of the parenchyma cells adjacent to lateral roots were observed. The high sensibility of C. cajan to As was confirmed, since it caused severe damages in root growth and anatomy. The main structural markers for As toxicity were the altered root architecture, with the reduction of the elongation zone and increase of ramification zone length, and the root primordia retained within the cortex. Our results show a new approach about As toxicity and indicate that C. cajan is a promising species to be used for bioindication of environmental contamination by As.

Exposure to the contraceptive progestin, gestodene, alters reproductive behavior, arrests egg deposition, and masculinizes development in the fathead minnow (Pimephales promelas)

USGS Publications Warehouse

Frankel, Tyler E.; Meyer, Michael T.; Kolpin, Dana W.; Gillis, Amanda B.; Alvarez, David A.; Orlando, Edward F.

2016-01-01

Endogenous progestogens and pharmaceutical progestins enter the environment through wastewater treatment plant effluent and agricultural field runoff. Lab studies demonstrate strong, negative exposure effects of these chemicals on aquatic vertebrate reproduction. Behavior can be a sensitive, early indicator of exposure to environmental contaminants associated with altered reproduction yet is rarely examined in ecotoxicology studies. Gestodene is a human contraceptive progestin and a potent activator of fish androgen receptors. Our objective was to test the effects of gestodene on reproductive behavior and associated egg deposition in the fathead minnow. After only 1 day, males exposed to ng/L of gestodene were more aggressive and less interested in courtship and mating, and exposed females displayed less female courtship behavior. Interestingly, 25% of the gestodene tanks contained a female that drove the male out of the breeding tile and displayed male-typical courtship behaviors toward the other female. Gestodene decreased or arrested egg deposition with no observed gonadal histopathology. Together, these results suggest that effects on egg deposition are primarily due to altered reproductive behavior. The mechanisms by which gestodene disrupts behavior are unknown. Nonetheless, the rapid and profound alterations of the reproductive biology of gestodene-exposed fish suggest that wild populations could be similarly affected.

Parkinson's disease and pesticides: A meta-analysis of disease connection and genetic alterations.

PubMed

Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M

2017-06-01

Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

PubMed Central

Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

2014-01-01

Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philbrook, Nicola A.; Winn, Louise M., E-mail: winnl@queensu.ca; School of Environmental Studies, Queen's University, Kingston, ON K7L3N6

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as wellmore » as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. - Highlights: • Benzene exposure in pregnant mice decreased global DNA methylation in maternal bone marrow. • Benzene exposure in pregnant mice had no effect on global DNA methylation in fetal livers. • No effect of benzene exposure was observed on p15 promoter methylation. • No effect of benzene on measured histone modifications in both maternal bone marrow and fetal livers was observed.« less

Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera).

PubMed

Christen, Verena; Mittner, Fabian; Fent, Karl

2016-04-05

Neonicotinoids are implicated in the decline of bee populations. As agonists of nicotinic acetylcholine receptors, they disturb acetylcholine receptor signaling leading to neurotoxicity. Several behavioral studies showed the link between neonicotinoid exposure and adverse effects on foraging activity and reproduction. However, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic levels of three neonicotinoids and nicotine, and compared laboratory studies to field exposures with acetamiprid. We assessed transcriptional alterations of eight selected genes in caged honey bees exposed to different concentrations of the neonicotinoids acetamiprid, clothianidin, imidacloporid, and thiamethoxam, as well as nicotine. We determined transcripts of several targets, including nicotinic acetylcholine receptor α 1 and α 2 subunit, the multifunctional gene vitellogenin, immune system genes apidaecin and defensin-1, stress-related gene catalase and two genes linked to memory formation, pka and creb. Vitellogenin showed a strong increase upon neonicotinoid exposures in the laboratory and field, while creb and pka transcripts were down-regulated. The induction of vitellogenin suggests adverse effects on foraging activity, whereas creb and pka down-regulation may be implicated in decreased long-term memory formation. Transcriptional alterations occurred at environmental concentrations and provide an explanation for the molecular basis of observed adverse effects of neonicotinoids to bees.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

PubMed

Arndt, David L; Peterson, Christy J; Cain, Mary E

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats

PubMed Central

Arndt, David L.; Peterson, Christy J.; Cain, Mary E.

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression. PMID:26154768

Effects of tributyltin (TBT) on Xenopus tropicalis embryos at environmentally relevant concentrations.

PubMed

Guo, Suzhen; Qian, Lijuan; Shi, Huahong; Barry, Terence; Cao, Qinzhen; Liu, Junqi

2010-04-01

Tributyltin (TBT) has been widely used as a biocide in antifouling paints and is a known endocrine disrupting chemical. In this paper, we exposed embryos of Xenopus tropicalis to 50-400ngL(-1) tributyltin chloride. TBT significantly decreased the survival rate, reduced the body length and retarded the development of embryos after 24, 36 and 48h of exposure. These effects of TBT were concentration- and time-dependent. Embryos treated with TBT showed multiple malformations. The most obvious alterations were abnormal eyes, enlarged proctodaeum, narrow fins, and skin hypopigmentation. Enlarged proctodaeum and narrow fins were mainly observed after 36 and 48h of exposure. The loss of eye pigmentation or the absence of external eyes occurred after 24 and 36h of exposure, while extended lenses or edemas of eyes were more commonly observed after 48h of exposure. Additional malformations included: small anterior region of heads, pericardial edemas, enlarged trunks, and bent tails. These results suggested that TBT is very toxic to X. tropicalis embryos at environmentally relevant concentrations.

Can environmental or occupational hazards alter the sex ratio at birth? A systematic review

PubMed Central

Terrell, Metrecia L.; Hartnett, Kathleen P.; Marcus, Michele

2011-01-01

More than 100 studies have examined whether environmental or occupational exposures of parents affect the sex ratio of their offspring at birth. For this review, we searched Medline and Web of Science using the terms ‘sex ratio at birth’ and ‘sex ratio and exposure’ for all dates, and reviewed bibliographies of relevant studies to find additional articles. This review focuses on exposures that have been the subject of at least four studies including polychlorinated biphenyls (PCBs), dioxins, pesticides, lead and other metals, radiation, boron, and g-forces. For paternal exposures, only dioxins and PCBs were consistently associated with sex ratios higher or lower than the expected 1.06. Dioxins were associated with a decreased proportion of male births, whereas PCBs were associated with an increased proportion of male births. There was limited evidence for a decrease in the proportion of male births after paternal exposure to DBCP, lead, methylmercury, non-ionizing radiation, ionizing radiation treatment for childhood cancer, boron, or g-forces. Few studies have found higher or lower sex ratios associated with maternal exposures. Studies in humans and animals have found a reduction in the number of male births associated with lower male fertility, but the mechanism by which environmental hazards might change the sex ratio has not yet been established. PMID:24149027

Animal models for probing the developmental basis of disease and dysfunction paradigm.

PubMed

Heindel, Jerrold J

2008-02-01

There is a major paradigm shift taking place in science that while simple is profound. The new paradigm suggests that susceptibility to disease is set in utero or neonatally as a result of the influences of nutrition and exposures to environmental stressors/toxicants. In utero nutrition and/or in utero or neonatal exposures to environmental toxicants alter susceptibility to disease later in life as a result of their ability to affect the programming of tissue function that occurs during development. This concept, which is still a hypothesis undergoing scientific testing and scrutiny, is called the developmental basis of health and disease. If true, then it says that the focus on disease prevention and intervention must change from the time of disease onset to perhaps decades prior: during the in utero and neonatal period. Perhaps the reason it has been so difficult to link environmental exposure to disease susceptibility is that scientists have been looking at the wrong time! Certainly, not all exposures that result in increased disease or dysfunction occur during development. This paradigm shift just suggests that this is a sensitive window of exposure that should be examined more thoroughly. This overview focuses on animal models for the assessment of this new scientific paradigm and the animal data that now supports it.

Does the Concept of “Sensitization” Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?

PubMed Central

Collip, Dina; Myin-Germeys, Inez; Van Os, Jim

2008-01-01

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as “sensitization,” facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder. PMID:18203757

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice.

PubMed

Ramsey, Kathryn A; Larcombe, Alexander N; Sly, Peter D; Zosky, Graeme R

2013-02-18

Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations.

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

PubMed Central

2013-01-01

Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

A MIXTURE OF THE "ANTIANDROGENS" LINURON AND BUTYL BENZYL PHTHALATE ALTERS SEXUAL DIFFERENTIATION OF THE MALE RAT IN A CUMULATIVE FASHION

EPA Science Inventory

Prenatal exposure to environmental chemicals that interfere with the androgen signaling pathway can cause permanent adverse effects on reproductive development in male rats. The objectives of this study were to 1) determine whether a documented antiandrogen butyl benzyl phthalate...

EVALUATION OF ALTERED SENSITIVITY OF OLDER ADULTS TO ENVIRONMENTAL AGENTS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING

EPA Science Inventory

The population of older Americans is increasing due to the aging of the Baby Boomers as well as an increase in the average life span. A number of physiological and biochemical changes occur during aging that could influence the relationship between exposure, dose, and response to...

In-silico structure activity relationship study of toxicity endpoints by QSAR modeling (SOT)

EPA Science Inventory

Several thousand chemicals were tested in 700 toxicity-related in-vitro HTS bioassays through the EPA’s ToxCast and Tox21 projects. This chemical set only covers a portion of the chemical space of interest for environmental exposure, leading to a need to fill data gaps with alter...

Delayed ovulation and pregnancy outcome: effect ofenvironmental toxicants on the neuroendocrine control of theovary

EPA Science Inventory

In the female rat, we have shown that a burst exposure to environmental toxicants known to alter noradrenergic function will block the ovulatory surge of LH when administered during a sensitive period on the day of vaginal proestrus. Such treatments will delay ovulation by 24 h a...

INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECTS MCF-7 CELLS FROM THE CYTOTOXIC AND GENOTOXIC EFFECTS OF ARSENITE

EPA Science Inventory

Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear wether HSP induction alters the damaging effects of environmental chemical ...

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

USGS Publications Warehouse

Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

2011-01-01

Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

USGS Publications Warehouse

Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.L.

2011-01-01

Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305. ng/L and 1104. ng/L) and SER (5.2. ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28. ng/L induced vitellogenin in male fish-a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. ?? 2011 Elsevier B.V.

In utero exposure and breast cancer development: an epigenetic perspective.

PubMed

Hill, Jacob; Hodsdon, Wendy

2014-01-01

The ubiquitous and detrimental disease of breast cancer requires continual research into new and alternative forms of treatment and prevention. The emerging field of epigenetics is beginning to unfold an array of contemporary approaches to reduce the risk and improve the clinical approach to breast cancer. The information contained in this non-systematic review highlights and expands on the estrogen-based model of breast cancer epigenetics to provide an overview of epigenetic alterations induced by nutrition and environmental exposure. The majority of evidence suggests that various sources of excess estrogen correlate to future breast cancer development. In addition, maternal macro- and micronutrient balance appear to play a role in genomic regulation, and preliminary data suggest that specific superfoods, such as blueberries, have a protective epigenetic effect. Identifying the influence of environmental toxicants, hormonal exposure, maternal nutrition, and maternal disease on fetal epigenetics may have potential for development of new therapeutic approaches for the prevention of breast cancer.

Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

PubMed Central

Robey, R.Brooks; Weisz, Judith; Kuemmerle, Nancy; Salzberg, Anna C.; Berg, Arthur; Brown, Dustin G.; Kubik, Laura; Palorini, Roberta; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Woodrick, Jordan; Scovassi, A.Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Williams, Graeme P.; Lowe, Leroy; Meyer, Joel; Martin, Francis L.; Bisson, William H.; Chiaradonna, Ferdinando; Ryan, Elizabeth P.

2015-01-01

Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested. PMID:26106140

Role of snow and cold environment in the fate and effects of nanoparticles and select organic pollutants from gasoline engine exhaust.

PubMed

Nazarenko, Yevgen; Kurien, Uday; Nepotchatykh, Oleg; Rangel-Alvarado, Rodrigo B; Ariya, Parisa A

2016-02-01

Exposure to vehicle exhaust can drive up to 70 % of excess lifetime cancer incidences due to air pollution in urban environments. Little is known about how exhaust-derived particles and organic pollutants, implicated in adverse health effects, are affected by freezing ambient temperatures and the presence of snow. Airborne particles and (semi)volatile organic constituents in dilute exhaust were studied in a novel low-temperature environmental chamber system containing natural urban snow under controlled cold environmental conditions. The presence of snow altered the aerosol size distributions of dilute exhaust in the 10 nm to 10 μm range and decreased the number density of the nanoparticulate (<100 nm) fraction of exhaust aerosols, yet increased the 100-150 nm fraction. Upon 1 hour exhaust exposure, the total organic carbon increased in the natural snow from 0.218 ± 0.014 to 0.539 ± 0.009 mg L(-1), and over 40 additional (semi)volatile organic compounds and a large number of exhaust-derived carbonaceous and likely organic particles were identified. The concentrations of benzene, toluene, ethylbenzene, and xylenes (BTEX) increased from near the detection limit to 52.48, 379.5, 242.7, and 238.1 μg kg(-1) (± 10 %), respectively, indicating the absorption of exhaust-derived toxic organic compounds by snow. The alteration of exhaust aerosol size distributions at freezing temperatures and in the presence of snow, accompanied by changes of the organic pollutant content in snow, has potential to alter health effects of human exposure to vehicle exhaust.

Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure

PubMed Central

Meeker, John D.; Benedict, Merle D.

2013-01-01

A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated. PMID:23888128

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Session 2: Personalised nutrition. Epigenomics: a basis for understanding individual differences?

PubMed

Mathers, John C

2008-11-01

Epigenetics encompasses changes to marks on the genome that are copied from one cell generation to the next, which may alter gene expression but which do not involve changes in the primary DNA sequence. These marks include DNA methylation (methylation of cytosines within CpG dinucleotides) and post-translational modifications (acetylation, methylation, phosphorylation and ubiquitination) of the histone tails protruding from nucleosome cores. The sum of genome-wide epigenetic patterns is known as the epigenome. It is hypothesised that altered epigenetic marking is a means through which evidence of environmental exposures (including nutritional status and dietary exposure) is received and recorded by the genome. At least some of these epigenetic marks are remembered through multiple cell generations and their effects may be revealed in altered gene expression and cell function. Altered epigenetic marking allows plasticity of phenotype in a fixed genotype. Despite their identical genotypes, monozygotic twins show increasing epigenetic diversity with age and with divergent lifestyles. Differences in epigenetic markings may explain some inter-individual variation in disease risk and in response to nutritional interventions.

Differential exposure, duration, and sensitivity of unionoidean bivalve life stages to environmental contaminants

USGS Publications Warehouse

Cope, W.G.; Bringolf, R.B.; Buchwalter, D.B.; Newton, T.J.; Ingersoll, C.G.; Wang, N.; Augspurger, T.; Dwyer, F.J.; Barnhart, M.C.; Neves, R.J.; Hammer, E.

2008-01-01

Freshwater mussels (superfamily Unionoidea) are in serious global decline and in urgent need of protection and conservation. The declines have been attributed to a wide array of human activities resulting in pollution and water-quality degradation, and habitat destruction and alteration. Linkages among poor water quality, pollutant sources, and mussel decline in rivers and streams have been associated with results of laboratory-based tests of specific pollutants. However, uncertainties remain about the relationship of laboratory data to actual contaminant exposure routes for various mussel species, life stages, and in the habitats occupied during these exposures. We evaluated the pathways of exposure to environmental pollutants for all 4 life stages (free glochidia, encysted glochidia, juveniles, adults) of unionoidean mussels and found that each life stage has both common and unique characteristics that contribute to observed differences in exposure and sensitivity. Free glochidia typically are exposed only briefly (e.g., seconds to days) through surface water, whereas adults sustain exposure over years to decades through surface water, pore water, sediment, and diet. Juveniles live largely burrowed in the sediment for the first 0 to 4 y of life. Thus, sediment, pore water, and diet are the predominant exposure routes for this life stage, but surface water also might contribute to exposure during certain periods and environmental conditions. The obligate parasitic stage (encysted glochidia stage) on a host fish might be exposed from surface water while partially encysted or from toxicants in host-fish tissue while fully encysted. Laboratory methods for testing for acute and chronic exposures in water have advanced, and toxicant-specific information has increased in recent years. However, additional research is needed to understand interactions of life history, habitat, and long-term exposure to contaminants through water, pore water, sediment, and diet so that the risks of environmental exposures can be properly assessed and managed. ?? 2008 by The North American Benthological Society.

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism.

PubMed

Yu, Li; Wu, YiMing; Wu, Bai-Lin

2015-10-01

Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

Changes in the acoustic environment alter the foraging and sheltering behaviour of the cichlid Amititlania nigrofasciata.

PubMed

McLaughlin, Kirsty Elizabeth; Kunc, Hansjoerg P

2015-07-01

Anthropogenic noise can affect behaviour across a wide range of species in both terrestrial and aquatic environments. However, behaviours might not be affected in isolation. Therefore, a more holistic approach investigating how environmental stressors, such as noise pollution, affect different behaviours in concert is necessary. Using tank-based noise exposure experiments, we tested how changes in the acoustic environment affect the behaviour of the cichlid Amatitlania nigrofasciata. We found that exposure to anthropogenic noise affected a couple of behaviours: an increase in sheltering was accompanied by a decrease in foraging. Our results highlight the multiple negative effects of an environmental stressor on an individual's behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

Before the first breath: prenatal exposures to air pollution and lung development.

PubMed

Veras, Mariana Matera; de Oliveira Alves, Nilmara; Fajersztajn, Lais; Saldiva, Paulo

2017-03-01

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and the Subsequent Germ Line

PubMed Central

Skinner, Michael K.; Haque, Carlos Guerrero-Bosagna M.; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R.

2013-01-01

A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203

Biotransformation, genotoxic, and histopathological effects of environmental contaminants in European eel (Anguilla anguilla L.).

PubMed

Pacheco, Mário; Santos, Maria Ana

2002-11-01

A prolonged toxicity study was carried out in young European eel (Anguilla anguilla L.) to evaluate the effects of environmental contaminants, namely, two individual standard compounds, benzo[a]pyrene (BaP) and dehydroabietic acid (DHAA), and a complex mixture, bleached kraft pulp mill effluent (BKPME). Fish were exposed to BaP (0.22, 0.45, and 0.9 microM) and BKPME (3.12%, 6.25%, and 12.5% (v/v)) for 3, 7, and 30 days and to DHAA (0.07, 0.15, and 0.30 microM) for 3, 7, 30, 90, and 180 days. The biomarkers include biotransformation and genotoxicity indicators, such as total ethoxyresorufin O-deethylase (EROD) activity and frequency of erythrocytic nuclear abnormalities (ENAs), respectively. Hematological dynamics was assessed as frequency of immature erythrocytes (IEs). Histopathological examinations were carried out for the highest concentrations and for 30 days and longer exposures. Total EROD increases significantly only after 180 days of DHAA exposure. However, significant ENA induction was generally observed during exposure to all contaminants tested. Nevertheless, some of the ENA results suggest an altered genotoxic response, which may arise either from short-term exposures to the highest contaminant levels or long-term exposures to the lowest contaminant levels. IE frequency decreased significantly after 30 days of exposure to 0.45 microM BaP and 180 days of exposure to the entire DHAA concentration range. Increased density of pigmented macrophage aggregates in 30-day BaP- and BKPME-exposed fish as well as in 90- and 180-day DHAA-exposed fish confirmed histopathological liver alterations. Bile accumulation in hepatocytes after BaP treatment, cytoplasmic vacuolization and cell atrophy following DHAA exposure, as well as liver loss of parenchymal cells in BKPME-exposed fish, were also detected. Dispersed necrosis and focal inflammation were observed in the livers of all treated groups. Fish exposed to DHAA and BKPME showed skin and gill disruption as well as kidney Malpighian corpuscle alterations. All 30-day-treated groups revealed intense spleen hemosiderosis, indicating increased erythrophagia. This splenic effect may be strongly correlated with the observed disappearance of ENAs. Neoplastic lesions were not found. A multibiomarker strategy, which includes EROD, ENA, and IE assays as well as histopathological studies, contributed to a better understanding of the global toxic process.

Cortisol Reactivity in Two-Year-Old Children Prenatally Exposed to Methamphetamine

PubMed Central

Kirlic, Namik; Newman, Elana; LaGasse, Linda L.; Derauf, Chris; Shah, Rizwan; Smith, Lynne M.; Arria, Amelia M.; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; Dellagrotta, Sheri; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.

2013-01-01

Objective: Until now, the functioning of the hypothalamic–pituitary–adrenal (HPA) axis in children with prenatal methamphetamine exposure (PME) had been unexamined. Previous research indicates that prenatal exposure to stimulant drugs is associated with dose-response alterations in neural growth and connectivity and consequent neurobehavioral deficits. In addition, children of drug-using parents are at an increased risk for exposure to chronic postnatal stress. In this preliminary study, we examined the associations of PME and postnatal environmental stress with cortisol stress reactivity in children with PME. Method: Participants were 2-year-old children (N = 123; 55.3% male) with PME from a multicenter longitudinal Infant, Development, Environment, and Lifestyle Study. Saliva samples were obtained before and after a stress-inducing separation task. Hierarchical multiple regression analyses examined prenatal drug exposure, methodological and postnatal stress covariates, and interactions between levels of PME and postnatal stress. Results: Mild to moderate potential for child physical abuse moderated increased cortisol reactivity in high exposed children with PME. Blunted cortisol reactivity was associated with caregiver’s postnatal alcohol use, child’s behavioral dysregulation, and the interaction between higher levels of PME and caregiver’s psychopathology. Conclusions: Consistent with the known effects of stimulant drugs and chronically stressful environments on the HPA axis and, thus, the toxic stress and allostatic load phenomena, our results imply that elevated PME may be associated with alterations in the programming of the HPA axis reflecting hyperactivity, which under significant and chronic environmental stress then may become hypoactive. PMID:23490574

Influences of Environmental Chemicals on Atopic Dermatitis.

PubMed

Kim, Kwangmi

2015-06-01

Atopic dermatitis is a chronic inflammatory skin condition including severe pruritus, xerosis, visible eczematous skin lesions that mainly begin early in life. Atopic dermatitis exerts a profound impact on the quality of life of patients and their families. The estimated lifetime prevalence of atopic dermatitis has increased 2~3 fold during over the past 30 years, especially in urban areas in industrialized countries, emphasizing the importance of life-style and environment in the pathogenesis of atopic diseases. While the interplay of individual genetic predisposition and environmental factors contribute to the development of atopic dermatitis, the recent increase in the prevalence of atopic dermatitis might be attributed to increased exposure to various environmental factors rather than alterations in human genome. In recent decades, there has been an increasing exposure to chemicals from a variety of sources. In this study, the effects of various environmental chemicals we face in everyday life - air pollutants, contact allergens and skin irritants, ingredients in cosmetics and personal care products, and food additives - on the prevalence and severity of atopic dermatitis are reviewed.

Negative impact of a cadmium concentration considered environmentally safe in Brazil on the cardiac performance of bullfrog tadpoles.

PubMed

Dal-Medico, S E; Rissoli, R Z; Gamero, F U; Victório, J A; Salla, R F; Abdalla, F C; Silva-Zacarin, E C M; Carvalho, C S; Costa, M J

2014-06-01

A drastic amphibian decline has been observed worldwide, which can be attributed (among other factors) to exposure to pollutants. Considering that cadmium corresponds to the most rapidly increasing trace metal in the environment, the aim of this work was to evaluate whether the exposure (2 and 16 days) of bullfrog tadpoles to this trace metal, at the concentration currently considered environmentally safe (at 1ppb) in class 1 and 2 waters by the Brazilian Environmental Council, can affect the cardiac performance of these animals. The acute exposure (2 days) of tadpoles to cadmium resulted in a marked bradycardic response, which was correlated with an incomplete cardiac relaxation, without any compensation by improved cardiac twitch force (Fc) or contraction velocity (TPT), nor even by cardiac hypertrophy. Indeed, after 16 days of exposure, the cardiac function of tadpoles became even more depressed due to a marked decrease in Fc, a prolongation of TPT, and also incomplete relaxation (i.e. increases in the ventricle resting tension), without changes in ventricle relative mass. Altogether, the cardiodepressive effects of cadmium (especially after more prolonged exposure periods) impose negative alterations on a tadpole׳s development and also impede adequate homeostatic adjustments to respond appropriately to the exposure to cadmium with increase in energetic demand to counteract the deleterious effects of the xenobiotic. These disturbances can impair tadpoles׳ growth, development and reproduction. It is a fact that allows us to strongly suggest that cadmium concentrations, which are currently considered environmentally safe in Brazil, should be revised. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress.

PubMed

Papale, Ligia A; Li, Sisi; Madrid, Andy; Zhang, Qi; Chen, Li; Chopra, Pankaj; Jin, Peng; Keleş, Sündüz; Alisch, Reid S

2016-12-01

Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently, we reported a genome-wide disruption of hippocampal 5hmC in male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined the genome-wide profile of hippocampal 5hmC in female mice following exposure to acute stress and identified 363 differentially hydroxymethylated regions (DhMRs) linked to known (e.g., Nr3c1 and Ntrk2) and potentially novel genes associated with stress response and psychiatric disorders. Integration of hippocampal expression data from the same female mice found stress-related hydroxymethylation correlated to altered transcript levels. Finally, characterization of stress-induced sex-specific 5hmC profiles in the hippocampus revealed 778 sex-specific acute stress-induced DhMRs some of which were correlated to altered transcript levels that produce sex-specific isoforms in response to stress. Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Meta-analysis on occupational exposure to pesticides--neurobehavioral impact and dose-response relationships.

PubMed

Meyer-Baron, Monika; Knapp, Guido; Schäper, Michael; van Thriel, Christoph

2015-01-01

While the health impact of high exposures to pesticides is acknowledged, the impact of chronic exposures in the absence of acute poisonings is controversial. A systematic analysis of dose-response relationships is still missing. Its absence may provoke alternative explanations for altered performances. Consequently, opportunities for health prevention in the occupational and environmental field may be missed. Objectives were (1) quantification of the neurotoxic impact of pesticides by an analysis of functional alterations in workers measured by neuropsychological performance tests, (2) estimates of dose-response relationships on the basis of exposure duration, and (3) exploration of susceptible subgroups. The meta-analysis employed a random effects model to obtain overall effects for individual performance tests. Twenty-two studies with a total of 1758 exposed and 1260 reference individuals met the inclusion criteria. At least three independent outcomes were available for twenty-six performance variables. Significant performance effects were shown in adults and referred to both cognitive and motor performances. Effect sizes ranging from dRE=-0.14 to dRE=-0.67 showed consistent outcomes for memory and attention. Relationships between effect sizes and exposure duration were indicated for individual performance variables and the total of measured performances. Studies on adolescents had to be analyzed separately due to numerous outliers. The large variation among outcomes hampered the analysis of the susceptibility in this group, while data on female workers was too scant for the analysis. Relationships exist between the impact of pesticides on performances and exposure duration. A change in test paradigms would help to decipher the impact more specifically. The use of biomarkers appropriate for lower exposures would allow a better prevention of neurotoxic effects due to occupational and environmental exposure. Intervention studies in adolescents seem warranted to specify their risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Perflurooctanoic Acid Induces Developmental Cardiotoxicity in ...

EPA Pesticide Factsheets

Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPAR_). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that d

Toxicant induced behavioural aberrations in larval zebrafish are dependent on minor methodological alterations.

PubMed

Fraser, Thomas W K; Khezri, Abdolrahman; Jusdado, Juan G H; Lewandowska-Sabat, Anna M; Henry, Theodore; Ropstad, Erik

2017-07-05

Alterations in zebrafish motility are used to identify neurotoxic compounds, but few have reported how methodology may affect results. To investigate this, we exposed embryos to bisphenol A (BPA) or tetrabromobisphenol A (TBBPA) before assessing larval motility. Embryos were maintained on a day/night cycle (DN) or in constant darkness, were reared in 96 or 24 well plates (BPA only), and behavioural tests were carried out at 96, 100, or 118 (BPA only) hours post fertilisation (hpf). We found that the prior photo-regime, larval age, and/or arena size influence behavioural outcomes in response to toxicant exposure. For example, methodology determined whether 10μM BPA induced hyperactivity, hypoactivity, or had no behavioural effect. Furthermore, the minimum effect concentration was not consistent between different methodologies. Finally, we observed a mechanism previously used to explain hyperactivity following BPA exposure does not appear to explain the hypoactivity observed following minor alterations in methodology. Therefore, we demonstrate how methodology can have notable implications on dose responses and behavioural outcomes in larval zebrafish motility following identical chemical exposures. As such, our results have significant consequences for human and environmental risk assessment. Copyright © 2017 Elsevier B.V. All rights reserved.

Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'.

PubMed

Englert, H; Champion, D; Wu, J C; Giallussi, J; McGrath, M; Manolios, N

2011-02-01

In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Environmental enrichment reverses memory impairment induced by toluene in mice.

PubMed

Montes, Sergio; Solís-Guillén, Rocío Del Carmen; García-Jácome, David; Páez-Martínez, Nayeli

2017-05-01

Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory. Copyright © 2017. Published by Elsevier Inc.

A new paradigm in toxicology and teratology: altering gene activity in the absence of DNA sequence variation.

PubMed

Reamon-Buettner, Stella Marie; Borlak, Jürgen

2007-07-01

'Epigenetics' is a heritable phenomenon without change in primary DNA sequence. In recent years, this field has attracted much attention as more epigenetic controls of gene activities are being discovered. Such epigenetic controls ensue from an interplay of DNA methylation, histone modifications, and RNA-mediated pathways from non-coding RNAs, notably silencing RNA (siRNA) and microRNA (miRNA). Although epigenetic regulation is inherent to normal development and differentiation, this can be misdirected leading to a number of diseases including cancer. All the same, many of the processes can be reversed offering a hope for epigenetic therapies such as inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases, histone deacetylases, and RNAi therapeutics. 'In utero' or early life exposures to dietary and environmental exposures can have a profound effect on our epigenetic code, the so-called 'epigenome', resulting in birth defects and diseases developed later in life. Indeed, examples are accumulating in which environmental exposures can be attributed to epigenetic causes, an encouraging edge towards greater understanding of the contribution of epigenetic influences of environmental exposures. Routine analysis of epigenetic modifications as part of the mechanisms of action of environmental contaminants is in order. There is, however, an explosion of research in the field of epigenetics and to keep abreast of these developments could be a challenge. In this paper, we provide an overview of epigenetic mechanisms focusing on recent reviews and studies to serve as an entry point into the realm of 'environmental epigenetics'.

Animal Models of Fetal Alcohol Spectrum Disorders: Impact of the Social Environment

PubMed Central

Kelly, Sandra J.; Goodlett, Charles R.; Hannigan, John H.

2013-01-01

Animal models of fetal alcohol spectrum disorder (FASD) have been used to demonstrate the specificity of alcohol’s teratogenic effects and some of the underlying changes in the central nervous system (CNS) and, more recently, to explore ways to ameliorate the effects of alcohol. The main point of this review is to highlight research findings from the animal literature which point to the impact of the social context or social behavior on the effect(s) of alcohol exposure during development, and also to point to research questions about the social environment and effects of prenatal alcohol exposure that remain to be answered. Alcohol exposure during early development alters maternal responding to the exposed pup in a variety of ways and the alteration in maternal responding could alter later stress responsivity and adult maternal and social behavior of the exposed offspring. Environmental enrichment and voluntary exercise have been shown to ameliorate some of alcohol’s impact during development, but the roles of enhanced social interactions in the case of enrichment and of social housing during voluntary exercise need to be more fully delineated. Similarly, the role of social context across the lifespan, such as social housing, social experiences, and contact with siblings, needs further study. Because of findings that alcohol during development alters DNA methylation patterns and that there are alterations in the maternal care of the alcohol-exposed offspring, epigenetic effects and their relationship to social behavior in animal models of FASD are likely to become a fruitful area of research. Because of the simpler social behavior and the short lifespan of rodents, animal models of FASD can be useful in determining how the social context impacts the effects of alcohol exposure during development. PMID:19731387

Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Jun; Graduate School of the Chinese Academy of Sciences, Beijing 100039; Liu Chunsheng

Tribromophenol (2,4,6-TBP) is ubiquitously found in aquatic environments and biota. In this study, we exposed zebrafish embryos (F{sub 0}; 2'''' days post-fertilization, dpf) to environmental concentration (0.3 mug/L) and a higher concentration (3.0 mug/L) of TBP and assessed the impact of chronic exposure (120 dpf) on reproduction. TBP exposure did not cause a significant increase in the malformation and reduction in the survival in the F{sub 0}-generation fish. After TBP exposure, the plasma testosterone and estradiol levels significantly increased in males and decreased in females. The transcription of steroidogenic genes (3beta-HSD, 17beta-HSD, CYP17, CYP19A, CYP19B) was significantly upregulated in themore » brain and testes in males and downregulated in the brain and ovary in females. TBP exposure significantly downregulated and upregulated the expression of VTG in the liver of female and male fish, respectively. Meanwhile, TBP exposure altered the sex ratio toward a male-dominant state. The F{sub 1}-generation larvae exhibited increased malformation, reduced survival, and retarded growth, suggesting that TBP in the aquatic environment has significant adverse effects on fish population.« less

The contribution of fetal drug exposure to temperament: potential teratogenic effects on neuropsychiatric risk.

PubMed

Weiss, Sandra J; St Jonn-Seed, Mary; Harris-Muchell, Carolyn

2007-08-01

Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. High risk children (n = 120) were followed from birth to 6 months of age to determine the effects of fetal drug exposure on temperament, after controlling for the child's gender, gestational age, medical morbidity, ethnicity, and maltreatment as well as the mother's stress, income adequacy, and quality of caregiving. Methods included medical chart review, questionnaires, and videotapes of mother-child interaction. Preliminary analyses indicated that fetal drug exposure was associated with both distractibility and intensity of children's responses to the environment at 6 months of age. After adjusting for potentially confounding variables, drug exposure accounted for 12% of the variance in distractibility but was not a significant predictor in the regression model for intensity. Findings suggest that drug-exposed children may experience difficulty sustaining their focus of attention and be more easily distracted by environmental stimuli than non-drug-exposed children. Results converge with previous research to implicate cortical hyperarousal, stemming from teratogenic effects on the dopaminergic system during fetal development.

Timing of light exposure affects mood and brain circuits

PubMed Central

Bedrosian, T A; Nelson, R J

2017-01-01

Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light–dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep–wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light exposure affects the brain. Converging evidence suggests that circadian disruption alters the function of brain regions involved in emotion and mood regulation. This occurs through direct neural input from the clock or indirect effects, including altered neuroplasticity, neurotransmission and clock gene expression. Recently, the aberrant light exposure has been recognized for its health effects. This review summarizes the evidence linking aberrant light exposure to mood. PMID:28140399

Evidence for carry-over effects of predator exposure on pathogen transmission potential.

PubMed

Roux, Olivier; Vantaux, Amélie; Roche, Benjamin; Yameogo, Koudraogo B; Dabiré, Kounbobr R; Diabaté, Abdoulaye; Simard, Frederic; Lefèvre, Thierry

2015-12-22

Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite Plasmodium falciparum, the mosquito vector Anopheles coluzzii and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to P. falciparum, it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology. © 2015 The Author(s).

Longitudinal effects of developmental bisphenol A and variable diet exposures on epigenetic drift in mice.

PubMed

Kochmanski, Joseph; Marchlewicz, Elizabeth H; Savidge, Matthew; Montrose, Luke; Faulk, Christopher; Dolinoy, Dana C

2017-03-01

Environmental factors, including exogenous exposures and nutritional status, can affect DNA methylation across the epigenome, but effects of exposures on age-dependent epigenetic drift remain unclear. Here, we tested the hypothesis that early-life exposure to bisphenol A (BPA) and/or variable diet results in altered epigenetic drift, as measured longitudinally via target loci methylation in paired mouse tail tissue (3 wks/10 mos old). Methylation was quantified at two repetitive elements (LINE-1, IAP), two imprinted genes (Igf2, H19), and one non-imprinted gene (Esr1) in isogenic mice developmentally exposed to Control, Control+BPA (50μg/kg diet), Mediterranean, Western, Mediterranean+BPA, or Western+BPA diets. Across age, methylation levels significantly (p<0.050) decreased at LINE-1, IAP, and H19, and increased at Esr1. Igf2 demonstrated Western-specific changes in early-life methylation (p=0.027), and IAP showed marginal negative modification of drift in Western (p=0.058) and Western+BPA (p=0.051). Thus, DNA methylation drifts across age, and developmental nutritional exposures can alter age-related methylation patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for carry-over effects of predator exposure on pathogen transmission potential

PubMed Central

Roux, Olivier; Vantaux, Amélie; Roche, Benjamin; Yameogo, Koudraogo B.; Dabiré, Kounbobr R.; Diabaté, Abdoulaye; Simard, Frederic; Lefèvre, Thierry

2015-01-01

Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite Plasmodium falciparum, the mosquito vector Anopheles coluzzii and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to P. falciparum, it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology. PMID:26674956

Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells

NASA Technical Reports Server (NTRS)

Schatten, H.; Lewis, M. L.; Chakrabarti, A.

2001-01-01

The cytoskeleton is a complex network of fibers that is sensitive to environmental factors including microgravity and altered gravitational forces. Cellular functions such as transport of cell organelles depend on cytoskeletal integrity; regulation of cytoskeletal activity plays a role in cell maintenance, cell division, and apoptosis. Here we report cytoskeletal and mitochondria alterations in cultured human lymphocyte (Jurkat) cells after exposure to spaceflight and in insect cells of Drosophila melanogaster (Schneider S-1) after exposure to conditions created by clinostat rotation. Jurkat cells were flown on the space shuttle in Biorack cassettes while Schneider S-1 cells were exposed to altered gravity forces as produced by clinostat rotation. The effects of both treatments were similar in the different cell types. Fifty percent of cells displayed effects on the microtubule network in both cell lines. Under these experimental conditions mitochondria clustering and morphological alterations of mitochondrial cristae was observed to various degrees after 4 and 48 hours of culture. Jurkat cells underwent cell divisions during exposure to spaceflight but a large number of apoptotic cells was also observed. Similar results were obtained in Schneider S-1 cells cultured under clinostat rotation. Both cell lines displayed mitochondria abnormalities and mitochondria clustering toward one side of the cells which is interpreted to be the result of microtubule disruption and failure of mitochondria transport along microtubules. The number of mitochondria was increased in cells exposed to altered gravity while cristae morphology was severely affected indicating altered mitochondria function. These results show that spaceflight as well as altered gravity produced by clinostat rotation affects microtubule and mitochondria organization and results in increases in apoptosis. Grant numbers: NAG 10-0224, NAG2-985. c 2001. Elsevier Science Ltd. All rights reserved.

Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish.

PubMed

Brown, D R; Bailey, J M; Oliveri, A N; Levin, E D; Di Giulio, R T

2016-01-01

Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 μg/L and 50.4 μg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in killifish, and that locomotor alterations could be observed in early larval stages. Additionally, our study highlights the resistance to behavioral alterations caused by low-level PAH mixture exposure in the adapted killifish population. Furthermore, this is the first longitudinal behavioral study to use killifish, an environmentally important estuarine teleost fish, and this testing framework can be used for future contaminant assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vivo Manganese Exposure Modulates Erk, Akt and Darpp-32 in the Striatum of Developing Rats, and Impairs Their Motor Function

PubMed Central

Cordova, Fabiano M.; Aguiar, Aderbal S.; Peres, Tanara V.; Lopes, Mark W.; Gonçalves, Filipe M.; Remor, Aline P.; Lopes, Samantha C.; Pilati, Célso; Latini, Alexandra S.; Prediger, Rui D. S.; Erikson, Keith M.; Aschner, Michael; Leal, Rodrigo B.

2012-01-01

Manganese (Mn) is an essential metal for development and metabolism. However, exposures to high Mn levels may be toxic, especially to the central nervous system (CNS). Neurotoxicity is commonly due to occupational or environmental exposures leading to Mn accumulation in the basal ganglia and a Parkinsonian-like disorder. Younger individuals are more susceptible to Mn toxicity. Moreover, early exposure may represent a risk factor for the development of neurodegenerative diseases later in life. The present study was undertaken to investigate the developmental neurotoxicity in an in vivo model of immature rats exposed to Mn (5, 10 and 20 mg/kg; i.p.) from postnatal day 8 (PN8) to PN12. Neurochemical analysis was carried out on PN14. We focused on striatal alterations in intracellular signaling pathways, oxidative stress and cell death. Moreover, motor alterations as a result of early Mn exposure (PN8-12) were evaluated later in life at 3-, 4- and 5-weeks-of-age. Mn altered in a dose-dependent manner the activity of key cell signaling elements. Specifically, Mn increased the phosphorylation of DARPP-32-Thr-34, ERK1/2 and AKT. Additionally, Mn increased reactive oxygen species (ROS) production and caspase activity, and altered mitochondrial respiratory chain complexes I and II activities. Mn (10 and 20 mg/kg) also impaired motor coordination in the 3rd, 4th and 5th week of life. Trolox™, an antioxidant, reversed several of the Mn altered parameters, including the increased ROS production and ERK1/2 phosphorylation. However, Trolox™ failed to reverse the Mn (20 mg/kg)-induced increase in AKT phosphorylation and motor deficits. Additionally, Mn (20 mg/kg) decreased the distance, speed and grooming frequency in an open field test; Trolox™ blocked only the decrease of grooming frequency. Taken together, these results establish that short-term exposure to Mn during a specific developmental window (PN8-12) induces metabolic and neurochemical alterations in the striatum that may modulate later-life behavioral changes. Furthermore, some of the molecular and behavioral events, which are perturbed by early Mn exposure are not directly related to the production of oxidative stress. PMID:22427945

Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI).

PubMed

Reed, Jessica L; D'Ambrosio, Enrico; Marenco, Stefano; Ursini, Gianluca; Zheutlin, Amanda B; Blasi, Giuseppe; Spencer, Barbara E; Romano, Raffaella; Hochheiser, Jesse; Reifman, Ann; Sturm, Justin; Berman, Karen F; Bertolino, Alessandro; Weinberger, Daniel R; Callicott, Joseph H

2018-01-01

Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes-catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)-and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited (total n = 487). We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex-COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.

Endocrine disruption of the epigenome: a breast cancer link

PubMed Central

Knower, Kevin C; To, Sarah Q; Leung, Yuet-Kin; Ho, Shuk-Mei; Clyne, Colin D

2015-01-01

The heritable component of breast cancer accounts for only a small proportion of total incidences. Environmental and lifestyle factors are therefore considered to among the major influencing components increasing breast cancer risk. Endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment. The estrogenic property of EDCs has thus shown many associations between ongoing exposures and the development of endocrine-related diseases, including breast cancer. The environment consists of a heterogenous population of EDCs and despite many identified modes of action, including that of altering the epigenome, drawing definitive correlations regarding breast cancer has been a point of much discussion. In this review, we describe in detail well-characterized EDCs and their actions in the environment, their ability to disrupt mammary gland formation in animal and human experimental models and their associations with exposure and breast cancer risk. We also highlight the susceptibility of early-life exposure to each EDC to mediate epigenetic alterations, and where possible describe how these epigenome changes influence breast cancer risk. PMID:24532474

Behavioural and biochemical responses to metals tested alone or in mixture (Cd-Cu-Ni-Pb-Zn) in Gammarus fossarum: From a multi-biomarker approach to modelling metal mixture toxicity.

PubMed

Lebrun, Jérémie D; Uher, Emmanuelle; Fechner, Lise C

2017-12-01

Metals are usually present as mixtures at low concentrations in aquatic ecosystems. However, the toxicity and sub-lethal effects of metal mixtures on organisms are still poorly addressed in environmental risk assessment. Here we investigated the biochemical and behavioural responses of Gammarus fossarum to Cu, Cd, Ni, Pb and Zn tested individually or in mixture (M2X) at concentrations twice the levels of environmental quality standards (EQSs) from the European Water Framework Directive. The same metal mixture was also tested with concentrations equivalent to EQSs (M1X), thus in a regulatory context, as EQSs are proposed to protect aquatic biota. For each exposure condition, mortality, locomotion, respiration and enzymatic activities involved in digestive metabolism and moult were monitored over a 120h exposure period. Multi-metric variations were summarized by the integrated biomarker response index (IBR). Mono-metallic exposures shed light on biological alterations occurring at environmental exposure levels in gammarids and depending on the considered metal and gender. As regards mixtures, biomarkers were altered for both M2X and M1X. However, no additive or synergistic effect of metals was observed comparing to mono-metallic exposures. Indeed, bioaccumulation data highlighted competitive interactions between metals in M2X, decreasing subsequently their internalisation and toxicity. IBR values indicated that the health of gammarids was more impacted by M1X than M2X, because of reduced competitions and enhanced uptakes of metals for the mixture at lower, EQS-like concentrations. Models using bioconcentration data obtained from mono-metallic exposures generated successful predictions of global toxicity both for M1X and M2X. We conclude that sub-lethal effects of mixtures identified by the multi-biomarker approach can lead to disturbances in population dynamics of gammarids. Although IBR-based models offer promising lines of enquiry to predict metal mixture toxicity, further studies are needed to confirm their predictive quality on larger ranges of metallic combinations before their use in field conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

The psychoactive pollutant fluoxetine compromises antipredator behaviour in fish.

PubMed

Martin, Jake M; Saaristo, Minna; Bertram, Michael G; Lewis, Phoebe J; Coggan, Timothy L; Clarke, Bradley O; Wong, Bob B M

2017-03-01

Pharmaceuticals are increasingly being detected in aquatic ecosystems worldwide. Particularly concerning are pharmaceutical pollutants that can adversely impact exposed wildlife, even at extremely low concentrations. One such contaminant is the widely prescribed antidepressant fluoxetine, which can disrupt neurotransmission and behavioural pathways in wildlife. Despite this, relatively limited research has addressed the behavioural impacts of fluoxetine at ecologically realistic exposure concentrations. Here, we show that 28-day fluoxetine exposure at two ecologically relevant dosages-one representing low surface water concentrations and another representing high effluent flow concentrations-alters antipredator behaviour in Eastern mosquitofish (Gambusia holbrooki). We found that fluoxetine exposure at the lower dosage resulted in increased activity levels irrespective of the presence or absence of a predatory dragonfly nymph (Hemianax papuensis). Additionally, irrespective of exposure concentration, fluoxetine-exposed fish entered the predator 'strike zone' more rapidly. In a separate experiment, fluoxetine exposure reduced mosquitofish freezing behaviour-a common antipredator strategy-following a simulated predator strike, although, in females, this reduction in behaviour was seen only at the lower dosage. Together, our findings suggest that fluoxetine can cause both non-monotonic and sex-dependent shifts in behaviour. Further, they demonstrate that exposure to fluoxetine at environmentally realistic concentrations can alter antipredator behaviour, with important repercussions for organismal fitness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental stress and epigenetic transgenerational inheritance.

PubMed

Skinner, Michael K

2014-09-05

Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newborn outcomes generationally. This ancestral stress promoted the epigenetic transgenerational inheritance of abnormalities in the great-grand offspring of the exposed gestating female. Several studies now support the role of environmental stress in promoting the epigenetic transgenerational inheritance of disease. Observations suggest ancestral environmental stress may be a component of disease etiology in the current population.

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.

PubMed

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.

Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

PubMed

Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

2012-11-30

Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Exposure to Bisphenol A Exacerbates Migraine-Like Behaviors in a Multibehavior Model of Rat Migraine

PubMed Central

Berman, Nancy E. J.

2014-01-01

Migraine is a common and debilitating neurological disorder suffered worldwide. Women experience this condition 3 times more frequently than men, with estrogen strongly implicated to play a role. Bisphenol A (BPA), a highly prevalent xenoestrogen, is known to have estrogenic activity and may have an effect in migraine onset, intensity, and duration through estrogen receptor signaling. It was hypothesized that BPA exposure exacerbates migraine symptoms through estrogen signaling and downstream activation of nociception related pathways. Utilizing a multibehavior model of migraine in ovariectomized female rats, changes in locomotion, light and sound sensitivity, grooming, and acoustic startle were examined. Furthermore, changes in the expression of genes related to estrogen (ERα, GPR30), and nociception (extracellular signal regulated kinase, ERK, sodium gated channel, Nav1.8, and fatty acid amide hydrolase, FAAH) were studied following behavioral experiments. The following results were obtained: BPA treatment significantly exacerbated migraine-like behaviors in rats. Rats exposed to BPA demonstrated decreased locomotion, exacerbated light and sound aversion, altered grooming habits, and enhanced startle reflexes. Furthermore, BPA exposure increased mRNA expression of estrogen receptors, total ERK mRNA and ERK activation, as well as Nav1.8, and FAAH mRNA, indicative of altered estrogen signaling and altered nociception. These results show that BPA, an environmentally pervasive xenoestrogen, exacerbates migraine-like behavior in a rat model and alters expression of estrogen and nociception-related genes. PMID:24189132

Radiation and chemical degradation of UVR protection characteristics of fabrics.

PubMed

Khazova, M; O'Hagan, J B; Grainger, K J-L

2007-01-01

Clothing can provide substantial protection against solar ultraviolet radiation (UVR) and quantifying the amount of protection can have useful applications to recreational, occupational and medical situations. However, exposure of fabrics to sunlight and sea water can alter their physical and chemical properties, resulting in a change of UVR attenuation characteristics. The objective of the current study was to evaluate the effects of environmental degradation of fabrics on their UVR protection characteristics. The methodologies applied in this study can be used also for the assessment of protective clothing against occupational exposure.

A Review of the Molecular Mechanisms of Chemically-Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

PubMed Central

Hoenerhoff, Mark J.; Hong, Hue Hua; Ton, Tai-Vu; Lahousse, Stephanie A.; Sills, Robert C.

2012-01-01

Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental carcinogens, we examine rodent tumors (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in cancer genes and epigenetic events that are associated with human cancer. Our NTP studies have identified several genetic alterations in chemically induced rodent neoplasms that are important in human cancer. Identification of such alterations in rodent models of chemical carcinogenesis caused by exposure to environmental contaminants, occupational chemicals, and other compounds lends further support that they are of potential human health risk. These studies also emphasize the importance of molecular evaluation of chemically induced rodent tumors for providing greater public health significance for NTP evaluated compounds. PMID:19846892

Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations.

PubMed

Kaushik, Gaurav; Xia, Yu; Pfau, Jean C; Thomas, Michael A

2017-11-20

Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10μM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.

PubMed

Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M

2017-02-01

Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these genes, which could be used as early biomarkers to prevent renal injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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 between stress exposure (via glucocorticoid actions) and infection impose resource trade-offs that shape optimal allocation between development and somatic function. As a result, critical disease windows are likely shaped by stress exposure because any conditions that induce changes in differentiation rates will alter the duration and susceptibility of organisms to stressors or disease. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

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

PubMed

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.

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

PubMed Central

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

Impact of Environmental Exposures on the Mutagenicity/Carcinogenicity of Heterocyclic Amines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Felton, J S; Knize, M G; Bennett, L M

2003-12-19

Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assessmore » the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.« less

Perinatal Exposure to Environmentally Relevant Levels of Bisphenol A Decreases Fertility and Fecundity in CD-1 Mice

PubMed Central

Cabaton, Nicolas J.; Wadia, Perinaaz R.; Rubin, Beverly S.; Zalko, Daniel; Schaeberle, Cheryl M.; Askenase, Michael H.; Gadbois, Jennifer L.; Tharp, Andrew P.; Whitt, Gregory S.; Sonnenschein, Carlos; Soto, Ana M.

2011-01-01

Background Perinatal exposure to low-doses of bisphenol A (BPA) results in alterations in the ovary, uterus, and mammary glands and in a sexually dimorphic region of the brain known to be important for estrous cyclicity. Objectives We aimed to determine whether perinatal exposure to environmentally relevant doses of BPA alters reproductive capacity. Methods Female CD-1 mice that were exposed to BPA at 0, 25 ng, 250 ng, or 25 μg/kg body weight (BW)/day or diethylstilbestrol (DES) at 10 ng/kg BW/day (positive control) from gestational day 8 through day 16 of lactation were continuously housed with proven breeder males for 32 weeks starting at 2 months of age. At each delivery, pups born to these mating pairs were removed. The cumulative number of pups, number of deliveries, and litter size were recorded. The purity of the BPA used in this and our previous studies was assessed using HPLC, mass spectrometry, and nuclear magnetic resonance. Results The forced breeding experiment revealed a decrease in the cumulative number of pups, observed as a nonmonotonic dose–response effect, and a decline in fertility and fecundity over time in female mice exposed perinatally to BPA. The BPA was 97% pure, with no evidence of contamination by other phenolic compounds. Conclusions Perinatal exposure to BPA leads to a dose-dependent decline in the reproductive capacity of female mice. The effects on the cumulative number of pups are comparable to those previously reported in mice developmentally exposed to DES, a compound well known to impair reproduction in women. This association suggests the possibility that early BPA exposure may also affect reproductive capacity in women. PMID:21126938

Impact of di-ethylhexylphthalate exposure on metabolic programming in P19 ECC-derived cardiomyocytes.

PubMed

Schaedlich, Kristina; Schmidt, Juliane-Susanne; Kwong, Wing Yee; Sinclair, Kevin D; Kurz, Randy; Jahnke, Heinz-Georg; Fischer, Bernd

2015-07-01

Di(2-ethylhexyl)phthalate (DEHP) is the most common plasticizer in plastic devices of everyday use. It is a ubiquitous environmental contaminant and primarily known to impair male gonadal development and fertility. Studies concerning the long-term effects of prenatal DEHP exposure on certain diseases [The Developmental Origins of Health and Disease paradigm (DOHaD) hypothesis] are scarce although it is proven that DEHP crosses the placenta. Rising environmental pollution during the last centuries coincides with an increasing prevalence of cardiovascular and metabolic diseases. We have investigated the effects of an early embryonic DEHP exposure at different developmental stages on cardiomyogenesis. We used an in-vitro model, the murine P19 embryonic carcinoma cell line (P19 ECC), mimicking early embryonic stages up to differentiated beating cardiomyocytes. P19 ECC were exposed to DEHP (5, 50, 100 µg ml(-1)) at the undifferentiated stage for 5 days and subsequently differentiated to beating cardiomyocytes. We analyzed the expression of metabolic (Pparg1, Fabp4 and Glut4), cardiac (Myh6, Gja1) and methylation (Dnmt1, Dnmt3a) marker genes by quantitative real-time PCR (qRT-PCR), beating rate and the differentiation velocity of the cells. The methylation status of Pparg1, Ppara and Glut4 was investigated by pyrosequencing. DEHP significantly altered the expression of all investigated genes. The beating rate and differentiation velocity were accelerated. Exposure to DEHP led to small but statistically significant increases in methylation of specific CpGs within Ppara and Pparg1, which otherwise were generally hypomethylated, but methylation of Glut4 was unaltered. Early DEHP exposure of P19 ECC alters the expression of genes associated with cellular metabolism and the functional features of cardiomyocytes. Copyright © 2014 John Wiley & Sons, Ltd.

Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

PubMed

Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

2017-02-01

There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

Epigenetics studies of fetal alcohol spectrum disorder: where are we now?

PubMed

Lussier, Alexandre A; Weinberg, Joanne; Kobor, Michael S

2017-03-01

Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field.

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

PubMed Central

Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

PubMed

Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

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

PubMed

Bolton, Jessica L; Marinero, Steven; Hassanzadeh, Tania; Natesan, Divya; Le, Dominic; Belliveau, Christine; Mason, S N; Auten, Richard L; Bilbo, Staci D

2017-01-01

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 (E)18, which switched to decreased volume by post-natal day (P)30 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 to the risk of neurodevelopmental disorders.

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

PubMed Central

Bolton, Jessica L.; Marinero, Steven; Hassanzadeh, Tania; Natesan, Divya; Le, Dominic; Belliveau, Christine; Mason, S. N.; Auten, Richard L.; Bilbo, Staci D.

2017-01-01

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 (E)18, which switched to decreased volume by post-natal day (P)30 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 to the risk of neurodevelopmental disorders. PMID:28620294

Environmental exposure to manganese and motor function of children in Mexico.

PubMed

Hernández-Bonilla, D; Schilmann, A; Montes, S; Rodríguez-Agudelo, Y; Rodríguez-Dozal, S; Solís-Vivanco, R; Ríos, C; Riojas-Rodríguez, H

2011-10-01

Occupational manganese (Mn) exposure has been associated with motor deficits in adult workers, but data on the potential effects of environmental exposure to Mn on the developing motor function for a children population is scarce. The aim of this study was to evaluate the association between exposure to Mn and motor function of school aged children. We conducted a cross-sectional study selecting 195 children (100 exposed and 95 unexposed) between 7 and 11 years old. The following tests were used to evaluate the motor function: Grooved pegboard, finger tapping, and Santa Ana test. Mn exposure was assessed by blood (MnB) and hair concentrations (MnH). We constructed linear regression models to evaluate the association between exposure to Mn and the different test scores adjusting for age, sex, maternal education, hemoglobin and blood lead. The median concentration of MnH and MnB was significantly higher in exposed (12.6 μg/g and 9.5 μg/L) compared to unexposed children (0.6 μg/g and 8.0 μg/L). The exposed children on average performed the grooved pegboard test faster, but made more errors, although these results did not reach statistical significance with neither one of the Mn exposure biomarkers. MnB showed an inverse association on the execution of the finger tapping test (average in 5 trials β -0.4, p=0.02), but no association was observed with MnH. A subtle negative association of Mn exposure on motor speed and coordination was shown. In adults, the main effect of environmental Mn exposure has been associated with motor skills, but these results suggest that such alterations are not the main effect on children. Copyright © 2011 Elsevier Inc. All rights reserved.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

Prenatal exposure to a common organophosphate insecticide delays motor development in a mouse model of idiopathic autism.

PubMed

De Felice, Alessia; Scattoni, Maria Luisa; Ricceri, Laura; Calamandrei, Gemma

2015-01-01

Autism spectrum disorders are characterized by impaired social and communicative skills and repetitive behaviors. Emerging evidence supported the hypothesis that these neurodevelopmental disorders may result from a combination of genetic susceptibility and exposure to environmental toxins in early developmental phases. This study assessed the effects of prenatal exposure to chlorpyrifos (CPF), a widely diffused organophosphate insecticide endowed with developmental neurotoxicity at sub-toxic doses, in the BTBR T+tf/J mouse strain, a validated model of idiopathic autism that displays several behavioral traits relevant to the autism spectrum. To this aim, pregnant BTBR mice were administered from gestational day 14 to 17 with either vehicle or CPF at a dose of 6 mg/kg/bw by oral gavages. Offspring of both sexes underwent assessment of early developmental milestones, including somatic growth, motor behavior and ultrasound vocalization. To evaluate the potential long-term effects of CPF, two different social behavior patterns typically altered in the BTBR strain (free social interaction with a same-sex companion in females, or interaction with a sexually receptive female in males) were also examined in the two sexes at adulthood. Our findings indicate significant effects of CPF on somatic growth and neonatal motor patterns. CPF treated pups showed reduced weight gain, delayed motor maturation (i.e., persistency of immature patterns such as pivoting at the expenses of coordinated locomotion) and a trend to enhanced ultrasound vocalization. At adulthood, CPF associated alterations were found in males only: the altered pattern of investigation of a sexual partner, previously described in BTBR mice, was enhanced in CPF males, and associated to increased ultrasonic vocalization rate. These findings strengthen the need of future studies to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders.

Issue Paper on Physiological and Behavioral Changes in ...

EPA Pesticide Factsheets

This issue paper provides a summary of information from the published literature related to behavioral and physiological changes during pregnancy and lactation that may affect women’s exposure or susceptibility to environmental contaminants, provides potentially useful exposure factor data for this population of women, and highlights data gaps. Background Exposures to environmental contaminants can pose a risk to pregnant women’s health, the developing fetus, children, and adults later in their lives. Assessing risks to this potentially susceptible population requires an understanding of the physiological and behavioral changes that occur during pregnancy and lactation. Many physiological and anatomical changes occur in a woman’s organ systems during the course of pregnancy and lactation. For example, blood volume and cardiac output increase during pregnancy, and other metabolic functions are altered to provide for the demands of the fetus. Nutritional demands are greater during pregnancy and lactation. There also are changes in behavior during both pregnancy and lactation. For example, water consumption during pregnancy and lactation increases. These behavioral and physiological changes can lead to different environmental exposures than these women might otherwise experience in the absence of pregnancy or lactation. The purpose of the issue paper is to provide a summary of data available on physiological and behavioral changes in pregnant a

Low dose trichloroethylene alters cytochrome P450 - 2C subfamily expression in the developing chick heart

PubMed Central

Makwana, Om; Ahles, Lauren; Lencinas, Alejandro; Selmin, Ornella I.; Runyan, Raymond B.

2013-01-01

Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al., 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 ppb and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens. PMID:22855351

Developmental Exposure of Mice to TCDD Elicits a Similar Uterine Phenotype in Adult Animals as Observed in Women with Endometriosis

PubMed Central

Nayyar, Tultul; Bruner-Tran, Kaylon L.; Piestrzeniewicz-Ulanska, Dagmara; Osteen, Kevin G.

2007-01-01

Whether environmental toxicants impact an individual woman’s risk for developing endometriosis remains uncertain. Although the growth of endometrial glands and stroma at extra-uterine sites is associated with retrograde menstruation, our studies suggest that reduced responsiveness to progesterone may increase the invasive capacity of endometrial tissue in women with endometriosis. Interestingly, our recent studies using isolated human endometrial cells in short-term culture suggest that experimental exposure to the environmental contaminant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) can alter the expression of progesterone receptor isotypes. Compared to adult exposure, toxicant exposure during development can exert a significantly greater biological impact, potentially affecting the incidence of endometriosis in adults. To address this possibility, we exposed mice to TCDD at critical developmental time points and subsequently examined uterine progesterone receptor expression and steroid responsive transforming growth factor-β2 expression in adult animals. We find that the uterine phenotype of toxicant-exposed mice is markedly similarly to the endometrial phenotype of women with endometriosis. PMID:17056225

Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

PubMed Central

Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

2014-01-01

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 expression patterns. These events may contribute to the development of pre-neoplastic and neoplastic lesions that manifest during adulthood. PMID:24988533

Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores.

PubMed

McCrae, K C; Rand, T; Shaw, R A; Mason, C; Oulton, M R; Hastings, C; Cherlet, T; Thliveris, J A; Mantsch, H H; MacDonald, J; Scott, J E

2001-03-01

Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.

Comment on "Exposure to mercury and Aroclor 1268 congeners in least terns (Sternula antillarum) in coastal Georgia, USA" by G. L. Robinson, G. L. Mills, A. H. Lindell, S. H. Schweitzer and S. M. Hernandez, Environmental Science: Processes & Impacts, 2015, 17, 1424.

PubMed

Fuchsman, P C; Henning, M H; Magar, V S

2016-02-01

In a recent paper published in this journal (Robinson et al., Environmental Science: Processes & Impacts, 2015, 17, 1424), Robinson et al. reported concentrations of Aroclor 1268 congeners in least tern eggs in coastal Georgia, USA. This comment describes important omissions in Robinson et al.'s interpretation of those egg concentrations that alter the overall conclusions of the least tern study.

Childhood trauma- and cannabis-associated microstructural white matter changes in patients with psychotic disorder: a longitudinal family-based diffusion imaging study.

PubMed

Domen, Patrick; Michielse, Stijn; Peeters, Sanne; Viechtbauer, Wolfgang; van Os, Jim; Marcelis, Machteld

2018-05-29

Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure. DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education. At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma. Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

The neurobiology of social environmental risk for schizophrenia: an evolving research field.

PubMed

Akdeniz, Ceren; Tost, Heike; Meyer-Lindenberg, Andreas

2014-04-01

Schizophrenia is a severe and complex brain disorder that usually manifests in early adulthood and disturbs a wide range of human functions. More than 100 years after its initial description, the pathophysiology of the disorder is still incompletely understood. Many epidemiological studies strongly suggest a complex interaction between genetic and environmental risk factors for the development of the disorder. While there is considerable evidence for a social environmental component of this risk, the links between adverse social factors and altered brain function have just come into focus. In the present review, we first summarize epidemiological evidence for the significance of social environmental risk factors, outline the role of altered social stress processing in mental illness, and review the latest experimental evidence for the neural correlates of social environmental risk for schizophrenia. The studies we have discussed in this review provide a selection of the current work in the field. We suggest that many of the social environmental risk factors may impact on perceived social stress and engage neural circuits in the brain whose functional and structural architecture undergoes detrimental change in response to prolonged exposure. We conclude that multidisciplinary approaches involving various fields and thoroughly constructed longitudinal designs are necessary to capture complex structure of social environmental risks.

Adult wheel access interaction with activity and boldness personality in Siberian dwarf hamsters (Phodopus sungorus).

PubMed

Kanda, L Leann; Abdulhay, Amir; Erickson, Caitlin

2017-05-01

Individual animal personalities interact with environmental conditions to generate differences in behavior, a phenomenon of growing interest for understanding the effects of environmental enrichment on captive animals. Wheels are common environmental enrichment for laboratory rodents, but studies conflict on how this influences behavior, and interaction of wheels with individual personalities has rarely been examined. We examined whether wheel access altered personality profiles in adult Siberian dwarf hamsters. We assayed animals in a tunnel maze twice for baseline personality, then again at two and at seven weeks after the experimental group was provisioned with wheels in their home cages. Linear mixed model selection was used to assess changes in behavior over time and across environmental gradient of wheel exposure. While animals showed consistent inter-individual differences in activity, activity personality did not change upon exposure to a wheel. Boldness also varies among individuals, and there is evidence for female boldness scores converging after wheel exposure, that is, opposite shifts in behavior by high and low boldness individuals, although sample size is too small for the mixed model results to be robust. In general, Siberian dwarf hamsters appear to show low behavioral plasticity, particularly in general activity, in response to running wheels. Copyright © 2017 Elsevier B.V. All rights reserved.

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Effects of short-chain chlorinated paraffins exposure on the viability and metabolism of human hepatoma HepG2 cells.

PubMed

Geng, Ningbo; Zhang, Haijun; Zhang, Baoqin; Wu, Ping; Wang, Feidi; Yu, Zhengkun; Chen, Jiping

2015-03-03

Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxic effects at environmentally relevant doses, limiting the evaluation of their health risks. In this study, cell viability assay and targeted metabolomic approach was used to evaluate the environmental dose (<100 μg/L) effect of SCCPs on HepG2 cells. Cell viability was found to be decreased with increases in exposure dose of SCCPs. Exposure for 48 h to C10-CPs resulted in a significant reduction in cell viability compared with 24 h, even at 1 μg/L. SCCPs exposure altered the intracellular redox status and caused significant metabolic disruptions. As a kind of peroxisome proliferator, SCCPs specifically stimulated the β-oxidation of unsaturated fatty acids and long-chain fatty acids. Meanwhile, SCCPs exposure disturbed glycolysis and amino acid metabolism, and led to the up-regulation of glutamate metabolism and urea cycle. The toxic effects of SCCPs might mainly involve the perturbation of energy production, protein biosynthesis, fatty acid metabolism, and ammonia recycling.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

Climate Change and Our Environment: The Effect on Respiratory and Allergic Disease

PubMed Central

Barnes, Charles S.; Alexis, Neil E.; Bernstein, Jonathan A.; Cohn, John R.; Demain, Jeffrey G.; Horner, Elliott; Levetin, Estelle; Nel, Andre; Phipatanakul, Wanda

2013-01-01

Climate change is a constant and ongoing process. It is postulated that human activities have reached a point at which we are producing global climate change. This article provides suggestions to help the allergist/environmental physician integrate recommendations about improvements in outdoor and indoor air quality and the likely response to predicted alterations in the earth’s environment into their patient’s treatment plan. Many changes that affect respiratory disease are anticipated. Examples of responses to climate change include energy reduction retrofits in homes that could potentially affect exposure to allergens and irritants, more hot sunny days that increase ozone-related difficulties, and rises in sea level or altered rainfall patterns that increase exposure to damp indoor environments. Climate changes can also affect ecosystems, manifested as the appearance of stinging and biting arthropods in new areas. Higher ambient carbon dioxide concentrations, warmer temperatures, and changes in floristic zones could potentially increase exposure to ragweed and other outdoor allergens, whereas green practices such as composting can increase allergen and irritant exposure. Finally, increased energy costs may result in urban crowding and human source pollution, leading to changes in patterns of infectious respiratory illnesses. Improved governmental controls on airborne pollutants could lead to cleaner air and reduced respiratory diseases but will meet strong opposition because of their effect on business productivity. The allergy community must therefore adapt, as physician and research scientists always have, by anticipating the needs of patients and by adopting practices and research methods to meet changing environmental conditions. PMID:23687635

Mercury and Hazardous Chemicals in Schools: A Manual for Students in Southeast Asia. EPA 747-R-08-002

ERIC Educational Resources Information Center

US Environmental Protection Agency, 2008

2008-01-01

Children and adolescents, up to approximately age 20, are more susceptible than adults to potential health risks from chemicals and environmental hazards. Hazardous chemicals can interrupt or alter the normal development of a child's body, leading to lasting damage. Since children are smaller than adults, similar levels of exposure to toxic…

Making an Effort to Feel Positive: Insecure Attachment in Infancy Predicts the Neural Underpinnings of Emotion Regulation in Adulthood

ERIC Educational Resources Information Center

Moutsiana, Christina; Fearon, Pasco; Murray, Lynne; Cooper, Peter; Goodyer, Ian; Johnstone, Tom; Halligan, Sarah

2014-01-01

Background: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. Methods: We utilised a 22-year longitudinal…

Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.

PubMed

Wise, Sarah K; Laury, Adrienne M; Katz, Elizabeth H; Den Beste, Kyle A; Parkos, Charles A; Nusrat, Asma

2014-05-01

Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier. Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure. Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. © 2014 ARS-AAOA, LLC.

The effects of demographic, social, and environmental characteristics on pathogen prevalence in wild felids across a gradient of urbanization

PubMed Central

Logan, Kenneth A.; Alldredge, Mat W.; Carver, Scott; Bevins, Sarah N.; Lappin, Michael; VandeWoude, Sue; Crooks, Kevin R.

2017-01-01

Transmission of pathogens among animals is influenced by demographic, social, and environmental factors. Anthropogenic alteration of landscapes can impact patterns of disease dynamics in wildlife populations, increasing the potential for spillover and spread of emerging infectious diseases in wildlife, human, and domestic animal populations. We evaluated the effects of multiple ecological mechanisms on patterns of pathogen exposure in animal populations. Specifically, we evaluated how ecological factors affected the prevalence of Toxoplasma gondii (Toxoplasma), Bartonella spp. (Bartonella), feline immunodeficiency virus (FIV), and feline calicivirus (FCV) in bobcat and puma populations across wildland-urban interface (WUI), low-density exurban development, and wildland habitat on the Western Slope (WS) and Front Range (FR) of Colorado during 2009–2011. Samples were collected from 37 bobcats and 29 pumas on the WS and FR. As predicted, age appeared to be positively related to the exposure to pathogens that are both environmentally transmitted (Toxoplasma) and directly transmitted between animals (FIV). In addition, WS bobcats appeared more likely to be exposed to Toxoplasma with increasing intraspecific space-use overlap. However, counter to our predictions, exposure to directly-transmitted pathogens (FCV and FIV) was more likely with decreasing space-use overlap (FCV: WS bobcats) and potential intraspecific contacts (FIV: FR pumas). Environmental factors, including urbanization and landscape covariates, were generally unsupported in our models. This study is an approximation of how pathogens can be evaluated in relation to demographic, social, and environmental factors to understand pathogen exposure in wild animal populations. PMID:29121060

Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation

PubMed Central

Zhang, Limin; Nichols, Robert G.; Correll, Jared; Murray, Iain A.; Tanaka, Naoki; Smith, Philip B.; Hubbard, Troy D.; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J.; Perdew, Gary H.

2015-01-01

Background Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. Objectives We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Methods Six-week-old male wild-type and Ahr–/– mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Results Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. Conclusion These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism. Citation Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, Hubbard TD, Sebastian A, Albert I, Hatzakis E, Gonzalez FJ, Perdew GH, Patterson AD. 2015. Persistent organic pollutants modify gut microbiota–host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ Health Perspect 123:679–688; http://dx.doi.org/10.1289/ehp.1409055 PMID:25768209

Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled

PubMed Central

2017-01-01

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized industrial chemicals worldwide, with the ability to interfere with/or mimic estrogenic hormones with associated biological responses. Environmental human exposure to this endocrine disruptor, mostly through oral intake, is considered a generalized phenomenon, particularly in developed countries. However, in the context of occupational exposure, non-dietary exposure sources (e.g., air and contact) cannot be underestimated. Here, we performed a review of the literature on BPA occupational exposure and associated health effects. Relevantly, the authors only identified 19 studies from 2009 to 2017 that demonstrate that occupationally exposed individuals have significantly higher detected BPA levels than environmentally exposed populations and that the detection rate of serum BPA increases in relation to the time of exposure. However, only 12 studies performed in China have correlated potential health effects with detected BPA levels, and shown that BPA-exposed male workers are at greater risk of male sexual dysfunction across all domains of sexual function; also, endocrine disruption, alterations to epigenetic marks (DNA methylation) and epidemiological evidence have shown significant effects on the offspring of parents exposed to BPA during pregnancy. This overview raises awareness of the dramatic and consistent increase in the production and exposure of BPA and creates urgency to assess the actual exposure of workers to this xenoestrogen and to evaluate potential associated adverse health effects. PMID:29051454

Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled.

PubMed

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-09-13

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized industrial chemicals worldwide, with the ability to interfere with/or mimic estrogenic hormones with associated biological responses. Environmental human exposure to this endocrine disruptor, mostly through oral intake, is considered a generalized phenomenon, particularly in developed countries. However, in the context of occupational exposure, non-dietary exposure sources (e.g., air and contact) cannot be underestimated. Here, we performed a review of the literature on BPA occupational exposure and associated health effects. Relevantly, the authors only identified 19 studies from 2009 to 2017 that demonstrate that occupationally exposed individuals have significantly higher detected BPA levels than environmentally exposed populations and that the detection rate of serum BPA increases in relation to the time of exposure. However, only 12 studies performed in China have correlated potential health effects with detected BPA levels, and shown that BPA-exposed male workers are at greater risk of male sexual dysfunction across all domains of sexual function; also, endocrine disruption, alterations to epigenetic marks (DNA methylation) and epidemiological evidence have shown significant effects on the offspring of parents exposed to BPA during pregnancy. This overview raises awareness of the dramatic and consistent increase in the production and exposure of BPA and creates urgency to assess the actual exposure of workers to this xenoestrogen and to evaluate potential associated adverse health effects.

Interacting Symbionts and Immunity in the Amphibian Skin Mucosome Predict Disease Risk and Probiotic Effectiveness

PubMed Central

Woodhams, Douglas C.; Brandt, Hannelore; Baumgartner, Simone; Kielgast, Jos; Küpfer, Eliane; Tobler, Ursina; Davis, Leyla R.; Schmidt, Benedikt R.; Bel, Christian; Hodel, Sandro; Knight, Rob; McKenzie, Valerie

2014-01-01

Pathogenesis is strongly dependent on microbial context, but development of probiotic therapies has neglected the impact of ecological interactions. Dynamics among microbial communities, host immune responses, and environmental conditions may alter the effect of probiotics in human and veterinary medicine, agriculture and aquaculture, and the proposed treatment of emerging wildlife and zoonotic diseases such as those occurring on amphibians or vectored by mosquitoes. Here we use a holistic measure of amphibian mucosal defenses to test the effects of probiotic treatments and to assess disease risk under different ecological contexts. We developed a non-invasive assay for antifungal function of the skin mucosal ecosystem (mucosome function) integrating host immune factors and the microbial community as an alternative to pathogen exposure experiments. From approximately 8500 amphibians sampled across Europe, we compared field infection prevalence with mucosome function against the emerging fungal pathogen Batrachochytrium dendrobatidis. Four species were tested with laboratory exposure experiments, and a highly susceptible species, Alytes obstetricans, was treated with a variety of temperature and microbial conditions to test the effects of probiotic therapies and environmental conditions on mucosome function. We found that antifungal function of the amphibian skin mucosome predicts the prevalence of infection with the fungal pathogen in natural populations, and is linked to survival in laboratory exposure experiments. When altered by probiotic therapy, the mucosome increased antifungal capacity, while previous exposure to the pathogen was suppressive. In culture, antifungal properties of probiotics depended strongly on immunological and environmental context including temperature, competition, and pathogen presence. Functional changes in microbiota with shifts in temperature provide an alternative mechanistic explanation for patterns of disease susceptibility related to climate beyond direct impact on host or pathogen. This nonlethal management tool can be used to optimize and quickly assess the relative benefits of probiotic therapies under different climatic, microbial, or host conditions. PMID:24789229

Combined exposure to Maneb and Paraquat alters transcriptional regulation of neurogenesis-related genes in mice models of Parkinson's disease.

PubMed

Desplats, Paula; Patel, Pruthul; Kosberg, Kori; Mante, Michael; Patrick, Christina; Rockenstein, Edward; Fujita, Masayo; Hashimoto, Makoto; Masliah, Eliezer

2012-09-28

Parkinson's disease (PD) is a multifactorial disease where environmental factors act on genetically predisposed individuals. Although only 5% of PD manifestations are associated with specific mutations, majority of PD cases are of idiopathic origin, where environment plays a prominent role. Concurrent exposure to Paraquat (PQ) and Maneb (MB) in rural workers increases the risk for PD and exposure of adult mice to MB/PQ results in dopamine fiber loss and decreased locomotor activity. While PD is characterized by neuronal loss in the substantia nigra, we previously showed that accumulation of α-synuclein in the limbic system contributes to neurodegeneration by interfering with adult neurogenesis. We investigated the effect of pesticides on adult hippocampal neurogenesis in two transgenic models: Line 61, expressing the human wild type SNCA gene and Line LRRK2(G2019S), expressing the human LRRK2 gene with the mutation G2019S. Combined exposure to MB/PQ resulted in significant reduction of neuronal precursors and proliferating cells in non-transgenic animals, and this effect was increased in transgenic mice, in particular for Line 61, suggesting that α-synuclein accumulation and environmental toxins have a synergistic effect. We further investigated the transcription of 84 genes with direct function on neurogenesis. Overexpresion of α-synuclein resulted in the downregulation of 12% of target genes, most of which were functionally related to cell differentiation, while LRRK2 mutation had a minor impact on gene expression. MB/PQ also affected transcription in non-transgenic backgrounds, but when transgenic mice were exposed to the pesticides, profound alterations in gene expression affecting 27% of the studied targets were observed in both transgenic lines. Gene enrichment analysis showed that 1:3 of those genes were under the regulation of FoxF2 and FoxO3A, suggesting a primary role of these proteins in the response to genetic and environmental cues. We report that adult neurogenesis is highly susceptible to multiple "risk factors" for PD, including α-synuclein accumulation, LRRK2 G2019 mutation and exposure to environmental toxins. We identified specific groups of genes that are responsive to each stressor, while uncovering a novel function for Fox transcription factors in PD.

A compromised liver alters polychlorinated biphenyl-mediated toxicity.

PubMed

Wahlang, Banrida; Perkins, Jordan T; Petriello, Michael C; Hoffman, Jessie B; Stromberg, Arnold J; Hennig, Bernhard

2017-04-01

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9mg/kg) or the PCB mixture, Arcolor1260 (20mg/kg) and analyzed for inflammatory, calorimetry and metabolic parameters. Consistent with the literature, MCD diet-fed mice demonstrated steatosis, indicative of a compromised liver. Mice fed the MCD-diet and subsequently exposed to PCB126 showed observable wasting syndrome leading to mortality. PCB126 and Aroclor1260 exposure worsened hepatic fibrosis exhibited by the MCD groups. Interestingly, PCB126 but not Aroclor1260 induced steatosis and inflammation in CD-fed mice. Mice with liver injury and subsequently exposed to PCBs also manifested metabolic disturbances due to alterations in hepatic gene expression. Furthermore, PCB exposure in MCD-fed mice led to extra-hepatic toxicity such as upregulated circulating inflammatory biomarkers, implicating endothelial cell dysfunction. Taken together, these results indicate that environmental pollution can exacerbate toxicity caused by diet-induced liver injury which may be partially due to dysfunctional energy homeostasis. This is relevant to PCB-exposed human cohorts who suffer from alcohol or diet-induced fatty liver diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

PubMed

Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

2017-10-01

Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T 3 ) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

PubMed

Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

2015-12-01

Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

A new method to study the change of miRNA-mRNA interactions due to environmental exposures.

PubMed

Petralia, Francesca; Aushev, Vasily N; Gopalakrishnan, Kalpana; Kappil, Maya; W Khin, Nyan; Chen, Jia; Teitelbaum, Susan L; Wang, Pei

2017-07-15

Integrative approaches characterizing the interactions among different types of biological molecules have been demonstrated to be useful for revealing informative biological mechanisms. One such example is the interaction between microRNA (miRNA) and messenger RNA (mRNA), whose deregulation may be sensitive to environmental insult leading to altered phenotypes. The goal of this work is to develop an effective data integration method to characterize deregulation between miRNA and mRNA due to environmental toxicant exposures. We will use data from an animal experiment designed to investigate the effect of low-dose environmental chemical exposure on normal mammary gland development in rats to motivate and evaluate the proposed method. We propose a new network approach-integrative Joint Random Forest (iJRF), which characterizes the regulatory system between miRNAs and mRNAs using a network model. iJRF is designed to work under the high-dimension low-sample-size regime, and can borrow information across different treatment conditions to achieve more accurate network inference. It also effectively takes into account prior information of miRNA-mRNA regulatory relationships from existing databases. When iJRF is applied to the data from the environmental chemical exposure study, we detected a few important miRNAs that regulated a large number of mRNAs in the control group but not in the exposed groups, suggesting the disruption of miRNA activity due to chemical exposure. Effects of chemical exposure on two affected miRNAs were further validated using breast cancer human cell lines. R package iJRF is available at CRAN. pei.wang@mssm.edu or susan.teitelbaum@mssm.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

USGS Publications Warehouse

Schoenfuss, Heiko L.; Furlong, Edward T.; Phillips, Patrick J.; Scott, Tia-Marie; Kolpin, Dana W.; Cetkovic-Cvrlje, Marina; Lesteberg, Kelsey E.; Rearick, Daniel C.

2016-01-01

Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

Influences of Environmental Chemicals on Atopic Dermatitis

PubMed Central

2015-01-01

Atopic dermatitis is a chronic inflammatory skin condition including severe pruritus, xerosis, visible eczematous skin lesions that mainly begin early in life. Atopic dermatitis exerts a profound impact on the quality of life of patients and their families. The estimated lifetime prevalence of atopic dermatitis has increased 2~3 fold during over the past 30 years, especially in urban areas in industrialized countries, emphasizing the importance of life-style and environment in the pathogenesis of atopic diseases. While the interplay of individual genetic predisposition and environmental factors contribute to the development of atopic dermatitis, the recent increase in the prevalence of atopic dermatitis might be attributed to increased exposure to various environmental factors rather than alterations in human genome. In recent decades, there has been an increasing exposure to chemicals from a variety of sources. In this study, the effects of various environmental chemicals we face in everyday life - air pollutants, contact allergens and skin irritants, ingredients in cosmetics and personal care products, and food additives - on the prevalence and severity of atopic dermatitis are reviewed. PMID:26191377

Histological observation of hairless mice skin after exposure to Simulated Solar Light: Comparison between the histological findings with different methodologies and 3R principle correlations.

PubMed

Hossy, Bryan Hudson; Leitão, Alvaro Augusto da Costa; Torres, Renata Bosco; Ramos-E-Silva, Marcia; Miguel, Nádia Campos de Oliveira; de Pádula, Marcelo

2018-03-01

Albino hairless mouse (AHM) has been used as a biological model in photodermatology. However, the experimental landscape is diverse to follow and need particular attention. Irradiation parameters were investigated for the development of a protocol to assess alterations in the AHM skin using Simulated Solar Light (SSL). The present study was compared with published articles (last 15 years) according to irradiation protocols, morphological findings to minimize animal suffering and UV exposure. Three groups: Control (G1), experimental - sunburn (G2) and skin photodamage assay (G3). G2 were immobilized and exposed to SSL once for 15, 30 and 45min. G3 were exposed to SSL, without immobilization, for 15min once a day for one week. The dorsal skin was analyzed using hematoxylin and eosin technique. G2 displayed different sunburn degrees. Based on the profile of the observed morphological alterations, a 15min irradiation was chosen as the exposure time to expose G3, without immobilization, for 5 consecutive days. These conditions produced the same morphological changes in the AHM with a shorter solar exposure time, without immobilizing the animals but using environmental exposure fluences, conforming to 3R (reduction - refinement - replacement) recommendations. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Benzene exposure is associated with epigenetic changes (Review).

PubMed

Fenga, Concettina; Gangemi, Silvia; Costa, Chiara

2016-04-01

Benzene is a volatile aromatic hydrocarbon solvent and is known as one of the predominant air pollutants in the environment. Chronic exposure to benzene is known to cause aplastic anemia and increased risk of acute myelogenous leukemia in humans. Although the mechanisms by which benzene causes toxicity remain to be fully elucidated, it is widely accepted that its metabolism is crucial to its toxicity, with involvement of one or more reactive metabolites. Novel approaches aimed at evaluating different mechanisms by which benzene can impact on human health by altering gene regulation have been developed. Among these novel approaches, epigenetics appears to be promising. The present review article summarizes the most important findings, reported from the literature, on epigenetic modifications correlated to benzene exposure. A computerized search in PubMed was performed in November 2014, using search terms, including 'benzene', 'epigenetic', 'histone modifications', 'DNA methylation' and 'microRNA'. Epidemiological and experimental studies have demonstrated the potential epigenetic effects of benzene exposure. Several of the epigenomic changes observed in response to environmental exposures may be mechanistically associated with susceptibility to diseases. However, further elucidation of the mechanisms by which benzene alters gene expression may improve prediction of the toxic potential of novel compounds introduced into the environment, and allow for more targeted and appropriate disease prevention strategies.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

NASA Astrophysics Data System (ADS)

Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

2017-04-01

Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

PubMed Central

Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

2017-01-01

Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs. PMID:28436478

Early postnatal ozone exposure alters rat nodose and jugular sensory neuron development

PubMed Central

Zellner, Leor C.; Brundage, Kathleen M.; Hunter, Dawn D.; Dey, Richard D.

2011-01-01

Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O3). Airway neurons can mediate airway inflammation through the release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O3 exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O3 exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O3 (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O3-exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O3 exposure significantly alters sensory neuron development. PMID:22140294

Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors.

PubMed

Eraslan, Evren; Akyazi, Ibrahim; Erg L-Ekiz, Elif; Matur, Erdal

2015-01-01

Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice

PubMed Central

Rubin, Beverly S.; Paranjpe, Maneesha; DaFonte, Tracey; Schaeberle, Cheryl; Soto, Ana M.; Obin, Martin; Greenberg, Andrew S.

2017-01-01

Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and adiposity, and to assess potential sex differences in this response. Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition. The effects were dose specific and sex specific and were influenced by the precise window of BPA exposure. The addition of peripubertal BPA exposure following the initial perinatal exposure exacerbated adverse effects in the females but appeared to reduce differences in body weight and body composition between control and BPA exposed males. Some effects of BPA on body weight and body composition showed a non-linear dose response. PMID:27496714

More than genes: the advanced fetal programming hypothesis.

PubMed

Hocher, Berthold

2014-10-01

Many lines of data, initial epidemiologic studies as well as subsequent extensive experimental studies, indicate that early-life events play a powerful role in influencing later suceptibility to certain chronic diseases. Such events might be over- or undernutrition, exposure to environmental toxins, but also changes in hormones, in particular stress hormones. Typically, those events are triggered by the environmental challenges of the mother. However, recent studies have shown that paternal environmental or nutritional factors affect the phenotype of the offspring as well. The maternal and paternal environmental factors act on the phenotype of the offspring via epigenetic modification of its genome. The advanced fetal programming hypothesis proposes an additional non-environmentally driven mechanism: maternal and also paternal genes may influence the maturating sperm, the oocyte, and later the embryo/fetus, leading to their epigenetic alteration. Thus, the observed phenotype of the offspring may be altered by maternal/paternal genes independent of the fetal genome. Meanwhile, several independent association studies in humans dealing with metabolic and neurological traits also suggest that maternal genes might affect the offspring phenotype independent of the transmission of that particular gene to the offspring. Considering the implications of this hypothesis, some conclusions drawn from transgenic or knockout animal models and based on the causality between a genetic alteration and a phenotype, need to be challenged. Possible implications for the development, diagnostic and therapy of human genetic diseases have to be investigated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

PubMed

Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

2015-12-07

Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

Immune response induced by major environmental pollutants through altering neutrophils in zebrafish larvae.

PubMed

Xu, Hongyan; Zhang, Xiaoyan; Li, Hankun; Li, Caixia; Huo, Xiao-Jing; Hou, Li-Ping; Gong, Zhiyuan

2018-06-06

Environmental pollutants may cause adverse effects on the immune system of aquatic organisms. However, the cellular effects of pollutants on fish immune system are largely unknown. Here, we exploited the transgenic zebrafish Tg(lysC:DsRed2) larva as a preliminary screening system to evaluate the potential inflammatory effects of environmental pollutants. Tg(lysC:DsRED2) larvae aged 7-day-postfertilization (7 dpf) were treated with selected environmental chemicals for 24 h (24 h) and the number of neutrophils were quantified using both image analysis and fluorescence activated cell sorting (FACS). We found that the numbers of neutrophils in the Tg(lysC:DsRED2) larvae were significantly increased by most of the organic chemicals tested, including E2 (17β-estradiol), BPA (Bisphenol-A), NDEA (N-nitrosodiethylamine), 4-NP (4-Nitrophenol) and Lindane (γ-hexachlorocyclohexane). Neutrophil numbers were also increased by all the metals tested (Na2HAsO4· 7H2O, Pb(NO3)2, HgCl 2 , CdCl2, CuSO 4 ·5H 2 O, ZnSO4, and K2Cr2O7). The only exception was TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), which significantly reduced the number of neutrophils after exposure. Additionally, the transcription of genes (lyz, mpo, tnfα and il8) related to fish immune system were significantly modulated upon exposure to some of the selected chemicals such as E2, TCDD, Cu and Cd. This study revealed that representatives of major categories of environmental pollutants could cause an acute inflammatory response in zebrafish larvae as shown by alterations in the neutrophils, which may imply a common immunotoxicity mechanism for most environmental pollutants. This study has also demonstrated that Tg(lyz:DsRed2) transgenic zebrafish is an excellent tool for screening environmental chemicals with potential inflammatory effects through FACS-facilitated neutrophil counting. Copyright © 2018 Elsevier B.V. All rights reserved.

Epigenetics studies of fetal alcohol spectrum disorder: where are we now?

PubMed Central

Lussier, Alexandre A; Weinberg, Joanne; Kobor, Michael S

2017-01-01

Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field. PMID:28234026

Neuronal Cellular Responses to Extremely Low Frequency Electromagnetic Field Exposure: Implications Regarding Oxidative Stress and Neurodegeneration

PubMed Central

Reale, Marcella; Kamal, Mohammad A.; Patruno, Antonia; Costantini, Erica; D'Angelo, Chiara; Pesce, Miko; Greig, Nigel H.

2014-01-01

Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1mT; frequency, 50-Hz) on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2 −, which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT activity and a rise in O2 − levels. Together these studies support the further evaluation of ELF-EMF exposure in cellular and in vivo preclinical models to define mechanisms potentially impacted in humans. PMID:25127118

In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirenko, Oksana, E-mail: oksana.sirenko@moldev.com

An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 h and effects on cardiomyocyte beating andmore » cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca{sup 2+} flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30 min of exposure. In contrast, after 24 h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. - Highlights: • The cardiotoxic potential of a broad range of environmental chemicals was evaluated. • Human iPSC cardiomyocytes were used for multiparametric in vitro profiling. • Dose-response relationships were established for functional and cytotoxicity assays. • Computational data integration provided chemical-specific bioactivity profiles. • An assessment of the profiles revealed chemical class-specific similarities.« less

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

PubMed

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.

Long-Term Effects of Environmental Endocrine Disruptors on Reproductive Physiology and Behavior

PubMed Central

Patisaul, Heather B.; Adewale, Heather B.

2009-01-01

It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs), either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates. PMID:19587848

Oxygen flux as an indicator of physiological stress in aquatic organisms: a real-time biomonitoring system of water quality

NASA Astrophysics Data System (ADS)

Sanchez, Brian C.; Yale, Gowri; Chatni, Rameez; Ochoa-Acuña, Hugo G.; Porterfield, D. Marshall; Mclamore, Eric S.; Sepúlveda, María S.

2009-05-01

The detection of harmful chemicals and biological agents in real time is a critical need for protecting water quality. We studied the real-time effects of five environmental contaminants with differing modes of action (atrazine, pentachlorophenol, cadmium chloride, malathion, and potassium cyanide) on respiratory oxygen consumption in 2-day post-fertilization fathead minnow (Pimephales promelas) eggs. Our objective was to assess the sensitivity of fathead minnow eggs using the self-referencing micro-optrode technique to detect instantaneous changes in oxygen consumption after brief exposures to low concentrations of contaminants. Oxygen consumption data indicated that the technique is indeed sensitive enough to reliably detect physiological alterations induced by all contaminants. After 2 h of exposure, we identified significant increases in oxygen consumption upon exposure to pentachlorophenol (100 and 1000 μg/L), cadmium chloride (0.0002 and 0.002 μg/L), and atrazine (150 μg/L). In contrast, we observed a significant decrease in oxygen flux after exposures to potassium cyanide (5.2, 22, and 44 μg/L) and atrazine (1500 μg/L). No effects were detected after exposures to malathion (200 and 340 μg/L). We have also tested the sensitivity of Daphnia magna embryos as another animal model for real-time environmental biomonitoring. Our results are so far encouraging and support further development of this technology as a physiologically coupled biomonitoring tool for the detection of environmental toxicants.

PROVIDING A BETTER UNDERSTANDING OF THE SCIENCE UNDERLYING THE EFFECTS, EXPOSURE, ASSESSMENT, AND MANAGEMENT OF EDCS: DOES MILD HYPOTHYROIDISM INDUCED BY ENVIRONMENTAL CONTAMINANTS IRREVERSIBLY ALTER CNS FUNCTION IN THE JUVENILE AND ADULT ANIMAL?

EPA Science Inventory

SUMMARY: The NTD research project on Endocrine-Disrupting Chemicals (EDC) is focused on the effects of thyroid hormone (TH) deficiencies on the developing brain and is one component of a larger NHEERL research program evaluating androgen, estrogen, and thyroid-disrupting chemical...

Alteration of Cingulate Long-Term Plasticity and Behavioral Sensitization to Inflammation by Environmental Enrichment

ERIC Educational Resources Information Center

Shum, Fanny W. F.; Wu, Long-Jun; Zhao, Ming-Gao; Toyoda, Hiroki; Xu, Hui; Ren, Ming; Pinaud, Raphael; Ko, Shanelle W.; Lee, Yong-Seok; Kaang, Bong-Kiun; Zhuo, Min

2007-01-01

Exposure to an enriched environment (EE) has been shown to induce cortical plasticity. Considerable amount of research is focused on the effects of EE in the hippocampus; however, effects of EE on other brain regions and the mechanisms involved are not well known. To investigate this, we induced cortical plasticity by placing mice in an EE for one…

Impact of environmental tobacco smoke exposure in women on oxidative stress in the antral follicle and assisted reproduction outcomes.

PubMed

Kazemi, Ashraf; Ramezanzadeh, Fatemeh; Esfahani, Mohammad Hosein Nasr; Saboor-Yaraghi, Ali Akbar; Nejat, Saharnaz; Rahimi-Foroshani, Abbas

2013-08-01

Cigarette smoke contains many oxidants and may alter the human reproduction by inducing oxidative stress (OS) in both active and passive smokers. This study was designed to evaluate the effect of environmental tobacco smoke (ETS) exposure on oxidative stress in the follicular fluid and the assisted reproduction outcomes. An observational prospective study was carried out on 236 infertile women, who underwent assisted reproduction cycles. The ETS exposure was assessed using self-reported ETS exposure and the cotinine level in follicular fluid. To evaluate the OS in follicular fluid (FF) malon-di-aldehyde (MDA) and total antioxidant capacity (TAC) were measured. The number of retrieved oocytes, rate of metaphase II stage oocytes, fertilization rate, good cleavage rate, and no-fragmented embryo rate were considered as the assisted reproduction outcomes. The results were adjusted for age, body mass index, duration, and etiology of infertility; P-values less than 0.05 were considered significant. The MDA and TAC levels in FF were not related to the self-report number of the weekly ETS exposure and cotinine levels in FF. Also, the number of retrieved oocytes, MII stage oocytes, fertilization rate, good cleavage rate, and no-fragmented embryo rate were not related to the cotinine level and weekly ETS exposure. However, in women whose cotinine levels in FF were lower and equal/above 3.5 ng/ml, the number of retrieved oocytes was higher (12.63 ± .71 vs. 9.28 ± 1.11, P = 0.01). The relationship between the MDA level and cleavage rate (Beta = -18.5, confidence interval-34.9 and-2.1, P < 0.05) was negatively significant and the relationship between the MII stage rate with TAC (Beta = 0.02, confidence interval 0.01 and 0.04, P < 0.05) was positively significant. The ETS exposure may alter the assisted reproduction success by influencing the number of available oocytes. Although, the OS in a follicular environment affect the ability of oocytes to reach the specific cleavage stages at appropriate time intervals, it does not mediate poor-assisted reproduction outcomes due to ETS exposure.

Impact of environmental tobacco smoke exposure in women on oxidative stress in the antral follicle and assisted reproduction outcomes

PubMed Central

Kazemi, Ashraf; Ramezanzadeh, Fatemeh; Esfahani, Mohammad Hosein Nasr; Saboor-Yaraghi, Ali Akbar; Nejat, Saharnaz; Rahimi-Foroshani, Abbas

2013-01-01

Background: Cigarette smoke contains many oxidants and may alter the human reproduction by inducing oxidative stress (OS) in both active and passive smokers. This study was designed to evaluate the effect of environmental tobacco smoke (ETS) exposure on oxidative stress in the follicular fluid and the assisted reproduction outcomes. Materials and Methods: An observational prospective study was carried out on 236 infertile women, who underwent assisted reproduction cycles. The ETS exposure was assessed using self-reported ETS exposure and the cotinine level in follicular fluid. To evaluate the OS in follicular fluid (FF) malon-di-aldehyde (MDA) and total antioxidant capacity (TAC) were measured. The number of retrieved oocytes, rate of metaphase II stage oocytes, fertilization rate, good cleavage rate, and no-fragmented embryo rate were considered as the assisted reproduction outcomes. The results were adjusted for age, body mass index, duration, and etiology of infertility; P-values less than 0.05 were considered significant. Results: The MDA and TAC levels in FF were not related to the self-report number of the weekly ETS exposure and cotinine levels in FF. Also, the number of retrieved oocytes, MII stage oocytes, fertilization rate, good cleavage rate, and no-fragmented embryo rate were not related to the cotinine level and weekly ETS exposure. However, in women whose cotinine levels in FF were lower and equal/above 3.5 ng/ml, the number of retrieved oocytes was higher (12.63 ± .71 vs. 9.28 ± 1.11, P = 0.01). The relationship between the MDA level and cleavage rate (Beta = −18.5, confidence interval-34.9 and-2.1, P < 0.05) was negatively significant and the relationship between the MII stage rate with TAC (Beta = 0.02, confidence interval 0.01 and 0.04, P < 0.05) was positively significant. Conclusion: The ETS exposure may alter the assisted reproduction success by influencing the number of available oocytes. Although, the OS in a follicular environment affect the ability of oocytes to reach the specific cleavage stages at appropriate time intervals, it does not mediate poor-assisted reproduction outcomes due to ETS exposure. PMID:24379845

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

PubMed

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

2017-10-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

In Vivo Determination of Mitochondrial Function Using Luciferase-Expressing Caenorhabditis elegans: Contribution of Oxidative Phosphorylation, Glycolysis, and Fatty Acid Oxidation to Toxicant-Induced Dysfunction.

PubMed

Luz, Anthony L; Lagido, Cristina; Hirschey, Matthew D; Meyer, Joel N

2016-08-01

Mitochondria are a target of many drugs and environmental toxicants; however, how toxicant-induced mitochondrial dysfunction contributes to the progression of human disease remains poorly understood. To address this issue, in vivo assays capable of rapidly assessing mitochondrial function need to be developed. Here, using the model organism Caenorhabditis elegans, we describe how to rapidly assess the in vivo role of the electron transport chain, glycolysis, or fatty acid oxidation in energy metabolism following toxicant exposure, using a luciferase-expressing ATP reporter strain. Alterations in mitochondrial function subsequent to toxicant exposure are detected by depleting steady-state ATP levels with inhibitors of the mitochondrial electron transport chain, glycolysis, or fatty acid oxidation. Differential changes in ATP following short-term inhibitor exposure indicate toxicant-induced alterations at the site of inhibition. Because a microplate reader is the only major piece of equipment required, this is a highly accessible method for studying toxicant-induced mitochondrial dysfunction in vivo. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

PubMed Central

Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

2012-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

Stream vulnerability to widespread and emergent stressors: a focus on unconventional oil and gas

USGS Publications Warehouse

Entrekin, Sally; Maloney, Kelly O.; Katherine E. Kapo,; Walters, Annika W.; Evans-White, Michelle A.; Klemow, Kenneth M.

2015-01-01

Multiple stressors threaten stream physical and biological quality, including elevated nutrients and other contaminants, riparian and in-stream habitat degradation and altered natural flow regime. Unconventional oil and gas (UOG) development is one emerging stressor that spans the U.S. UOG development could alter stream sedimentation, riparian extent and composition, in-stream flow, and water quality. We developed indices to describe the watershed sensitivity and exposure to natural and anthropogenic disturbances and computed a vulnerability index from these two scores across stream catchments in six productive shale plays. We predicted that catchment vulnerability scores would vary across plays due to climatic, geologic and anthropogenic differences. Across-shale averages supported this prediction revealing differences in catchment sensitivity, exposure, and vulnerability scores that resulted from different natural and anthropogenic environmental conditions. For example, semi-arid Western shale play catchments (Mowry, Hilliard, and Bakken) tended to be more sensitive to stressors due to low annual average precipitation and extensive grassland. Catchments in the Barnett and Marcellus-Utica were naturally sensitive from more erosive soils and steeper catchment slopes, but these catchments also experienced areas with greater UOG densities and urbanization. Our analysis suggested Fayetteville and Barnett catchments were vulnerable due to existing anthropogenic exposure. However, all shale plays had catchments that spanned a wide vulnerability gradient. Our results identify vulnerable catchments that can help prioritize stream protection and monitoring efforts. Resource managers can also use these findings to guide local development activities to help reduce possible environmental effects.

Stream Vulnerability to Widespread and Emergent Stressors: A Focus on Unconventional Oil and Gas

PubMed Central

Entrekin, Sally A.; Maloney, Kelly O.; Kapo, Katherine E.; Walters, Annika W.; Evans-White, Michelle A.; Klemow, Kenneth M.

2015-01-01

Multiple stressors threaten stream physical and biological quality, including elevated nutrients and other contaminants, riparian and in-stream habitat degradation and altered natural flow regime. Unconventional oil and gas (UOG) development is one emerging stressor that spans the U.S. UOG development could alter stream sedimentation, riparian extent and composition, in-stream flow, and water quality. We developed indices to describe the watershed sensitivity and exposure to natural and anthropogenic disturbances and computed a vulnerability index from these two scores across stream catchments in six productive shale plays. We predicted that catchment vulnerability scores would vary across plays due to climatic, geologic and anthropogenic differences. Across-shale averages supported this prediction revealing differences in catchment sensitivity, exposure, and vulnerability scores that resulted from different natural and anthropogenic environmental conditions. For example, semi-arid Western shale play catchments (Mowry, Hilliard, and Bakken) tended to be more sensitive to stressors due to low annual average precipitation and extensive grassland. Catchments in the Barnett and Marcellus-Utica were naturally sensitive from more erosive soils and steeper catchment slopes, but these catchments also experienced areas with greater UOG densities and urbanization. Our analysis suggested Fayetteville and Barnett catchments were vulnerable due to existing anthropogenic exposure. However, all shale plays had catchments that spanned a wide vulnerability gradient. Our results identify vulnerable catchments that can help prioritize stream protection and monitoring efforts. Resource managers can also use these findings to guide local development activities to help reduce possible environmental effects. PMID:26397727

Long-term behavioral consequences of prenatal MDMA exposure.

PubMed

Thompson, Valerie B; Heiman, Justin; Chambers, James B; Benoit, Stephen C; Buesing, William R; Norman, Mantana K; Norman, Andrew B; Lipton, Jack W

2009-03-23

The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.

Biomonitoring of gasoline station attendants exposed to benzene: Effect of gender.

PubMed

Moro, Angela M; Brucker, Natália; Charão, Mariele F; Baierle, Marília; Sauer, Elisa; Goethel, Gabriela; Barth, Anelise; Nascimento, Sabrina N; Gauer, Bruna; Durgante, Juliano; Amaral, Beatriz S; Neto, Francisco R A; Gioda, Adriana; Garcia, Solange C

2017-01-01

Women are employed in increasing numbers as gasoline station attendants, a work category with risk of exposure to benzene. We have assessed the effect of gender on biomarkers of occupational benzene exposure. Gasoline station attendants (20 men and 20 women) and 40 control individuals (20 men and 20 women) with no history of occupational benzene exposure were evaluated. Benzene exposure was monitoring by environmental and biological measurements. Urinary trans,trans-muconic acid levels, well-known genetic and hematological alterations linked to benzene exposure, and non-cancer effects on the immune, hepatic, and renal systems were investigated. Our results suggest a potential effect of gender on some effects of occupational benzene exposure, particularly the hematological parameters and trans,trans-muconic acid levels. Despite limitations of our study, our findings provide important considerations about occupational exposure of women to benzene and may contribute to the development of occupational protection standards. Copyright © 2016 Elsevier B.V. All rights reserved.

Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behaviour and neuroendocrine systems.

PubMed

Frye, C A; Bo, E; Calamandrei, G; Calzà, L; Dessì-Fulgheri, F; Fernández, M; Fusani, L; Kah, O; Kajta, M; Le Page, Y; Patisaul, H B; Venerosi, A; Wojtowicz, A K; Panzica, G C

2012-01-01

Some environmental contaminants interact with hormones and may exert adverse consequences as a result of their actions as endocrine disrupting chemicals (EDCs). Exposure in people is typically a result of contamination of the food chain, inhalation of contaminated house dust or occupational exposure. EDCs include pesticides and herbicides (such as dichlorodiphenyl trichloroethane or its metabolites), methoxychlor, biocides, heat stabilisers and chemical catalysts (such as tributyltin), plastic contaminants (e.g. bisphenol A), pharmaceuticals (i.e. diethylstilbestrol; 17α-ethinylestradiol) or dietary components (such as phytoestrogens). The goal of this review is to address the sources, effects and actions of EDCs, with an emphasis on topics discussed at the International Congress on Steroids and the Nervous System. EDCs may alter reproductively-relevant or nonreproductive, sexually-dimorphic behaviours. In addition, EDCs may have significant effects on neurodevelopmental processes, influencing the morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more dangerous if it occurs during specific 'critical periods' of life, such as intrauterine, perinatal, juvenile or puberty periods, when organisms are more sensitive to hormonal disruption, compared to other periods. However, exposure to EDCs in adulthood can also alter physiology. Several EDCs are xenoestrogens, which can alter serum lipid concentrations or metabolism enzymes that are necessary for converting cholesterol to steroid hormones. This can ultimately alter the production of oestradiol and/or other steroids. Finally, many EDCs may have actions via (or independent of) classic actions at cognate steroid receptors. EDCs may have effects through numerous other substrates, such as the aryl hydrocarbon receptor, the peroxisome proliferator-activated receptor and the retinoid X receptor, signal transduction pathways, calcium influx and/or neurotransmitter receptors. Thus, EDCs, from varied sources, may have organisational effects during development and/or activational effects in adulthood that influence sexually-dimorphic, reproductively-relevant processes or other functions, by mimicking, antagonising or altering steroidal actions. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

ENDOCRINE DISRUPTERS: A REVIEW OF SOME SOURCES, EFFECTS, AND MECHANISMS OF ACTIONS ON BEHAVIOR AND NEUROENDOCRINE SYSTEMS

PubMed Central

Frye, C.; Bo, E.; Calamandrei, G.; Calzà, L.; Dessì-Fulgheri, F.; Fernández, M.; Fusani, L.; Kah, O.; Kajta, M.; Le Page, Y.; Patisaul, H.B.; Venerosi, A.; Wojtowicz, A.K.; Panzica, G.C.

2011-01-01

Some environmental contaminants interact with hormones and may exert adverse consequences due to their actions as endocrine disrupting chemicals (EDCs). Exposure in people is typically due to contamination of the food chain, inhalation of contaminated house dust, or occupational exposure. EDCs include pesticides and herbicides (such as diphenyl-dichloro-trichloroethane, DDT, or its metabolites), methoxychlor, biocides, heat stabilizers and chemical catalysts (such as tributyltin, TBT), plastic contaminants (e.g. bisphenol A, BPA), pharmaceuticals (i.e. diethylstilbestrol, DES; 17alpha-ethynilestradiol, EE2), or dietary components (such as phytoestrogens). The goal of this review is to address sources, effects and actions of EDCs, with an emphasis on topics discussed at the International Congress on Steroids and the Nervous System. EDCs may alter reproductively-relevant or non-reproductive, sexually-dimorphic behaviors. In addition, EDCs may have significant effects on neurodevelopmental processes, influencing morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more dangerous if it occurs during specific “critical periods” of life, such as intrauterine, perinatal, juvenile or puberty periods, when organisms are more sensitive to hormonal disruption, than in other periods. However, exposure to EDCs in adulthood also can alter physiology. Several EDCs are xenoestrogens, may alter serum lipid concentrations, or metabolism enzymes that are necessary for converting cholesterol to steroid hormones, ultimately altering production of E2 and/or other steroids. Finally, many EDCs may have actions via, or independent of, classic actions at cognate steroid receptors. EDCs may have effects through numerous other substrates, such as the aryl hydrocarbon receptor (AhR), the peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR), signal transduction pathways, calcium influx, and/or neurotransmitter receptors. Thus, EDCs, from varied sources, may have organizational effects during development, and/or activational effects in adulthood, that influence sexually-dimorphic, reproductively-relevant processes or other functions, by mimicking, antagonizing, or altering steroidal actions. PMID:21951193

Epigenetics as a mechanism linking developmental exposures to long-term toxicity.

PubMed

Barouki, R; Melén, E; Herceg, Z; Beckers, J; Chen, J; Karagas, M; Puga, A; Xia, Y; Chadwick, L; Yan, W; Audouze, K; Slama, R; Heindel, J; Grandjean, P; Kawamoto, T; Nohara, K

2018-05-01

A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

PubMed Central

Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

2011-01-01

Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung.

PubMed

Izzotti, Alberto; Larghero, Patrizia; Longobardi, Mariagrazia; Cartiglia, Cristina; Camoirano, Anna; Steele, Vernon E; De Flora, Silvio

2011-12-01

Our previous studies demonstrated that exposure to cigarette smoke (CS), either mainstream or environmental, results in a remarkable downregulation of microRNA expression in the lung of both mice and rats. The goals of the present study were to evaluate the dose responsiveness to CS and the persistence of microRNA alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole-body to mainstream CS, at the doses of 119, 292, 438, and 631mg/m(3) of total particulate matter. Exposure started within 12h after birth and continued daily for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were measured by (32)P postlabeling procedures, and the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS dose was lethal. Exposure to CS caused a dose-dependent increase of DNA alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4 weeks after smoking cessation. Exposure to CS resulted in an evident dysregulation of microRNA expression profiles, mainly in the sense of downregulation. The two lowest doses were not particularly effective, while the highest nonlethal dose produced extensive microRNA alterations. The expression of most downregulated microRNAs, including among others 7 members of the let-7 family, was restored one week after smoking cessation. However, the recovery was incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421, mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as biomarkers of effect and that exposure to high-dose, lasting for an adequate period of time, is needed to trigger the CS-related carcinogenesis process in the experimental animal model used. Copyright © 2011 Elsevier B.V. All rights reserved.

Muscarinic receptors mediate the endocrine-disrupting effects of an organophosphorus insecticide in zebrafish.

PubMed

Santos da Rosa, João Gabriel; Alcântara Barcellos, Heloísa Helena de; Fagundes, Michele; Variani, Cristiane; Rossini, Mainara; Kalichak, Fabiana; Koakoski, Gessi; Acosta Oliveira, Thiago; Idalencio, Renan; Frandoloso, Rafael; Piato, Angelo L; José Gil Barcellos, Leonardo

2017-07-01

The glucocorticoid cortisol, the end product of hypothalamus-pituitary-interrenal axis in zebrafish (Danio rerio), is synthesized via steroidogenesis and promotes important physiological regulations in response to a stressor. The failure of this axis leads to inability to cope with environmental challenges preventing adaptive processes in order to restore homeostasis. Pesticides and agrichemicals are widely used, and may constitute an important class of environmental pollutants when reach aquatic ecosystems and nontarget species. These chemical compounds may disrupt hypothalamus-pituitary-interrenal axis by altering synthesis, structure or function of its constituents. We present evidence that organophosphorus exposure disrupts stress response by altering the expression of key genes of the neural steroidogenesis, causing downregulation of star, hsp70, and pomc genes. This appears to be mediated via muscarinic receptors, since the muscarinic antagonist scopolamine blocked these effects. © 2017 Wiley Periodicals, Inc.

Adverse morphological development in embryonic zebrafish exposed to environmental concentrations of contaminants individually and in mixture.

PubMed

Kinch, Cassandra D; Kurrasch, Deborah M; Habibi, Hamid R

2016-06-01

Exposure to environmental contaminants has been linked to developmental and reproductive abnormalities leading to infertility, spontaneous abortion, reduced number of offspring, and metabolic disorders. In addition, there is evidence linking environmental contaminants and endocrine disruption to abnormal developmental rate, defects in heart and eye morphology, and alterations in behavior. Notably, these effects could not be explained by interaction with a single hormone receptor. Here, using a whole-organism approach, we investigated morphological changes to developing zebrafish caused by exposure to a number of environmental contaminants, including bisphenol A (BPA), di(2-ethylhexyl)phthalate (DEHP), nonylphenol, and fucosterol at concentrations measured in a local water body (Oldman River, AB), individually and in mixture. Exposure to nanomolar contaminant concentrations resulted in abnormal morphological development, including changes to body length, pericardia (heart), and the head. We also characterize the spatiotemporal expression profiles of estrogen, androgen, and thyroid hormone receptors to demonstrate that localization of these receptors might be mediating contaminant effects on development. Finally, we examined the effects of contaminants singly and in mixture. Combined, our results support the hypothesis that adverse effects of contaminants are not mediated by single hormone receptor signaling, and adversity of contaminants in mixture could not be predicted by simple additive effect of contaminants. The findings provide a framework for better understanding of developmental toxicity of environmental contaminants in zebrafish and other vertebrate species. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

De La Riva, Deborah G; Trumble, John T

2016-06-01

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Climate change and our environment: the effect on respiratory and allergic disease.

PubMed

Barne, Charles; Alexis, Neil E; Bernstein, Jonathan A; Cohn, John R; Demain, Jeffrey G; Horner, Elliot; Levetin, Estelle; Nei, Andre; Phipatanakul, Wanda

2013-03-01

Climate change is a constant and ongoing process. It is postulated that human activities have reached a point at which we are producing global climate change. It provides suggestions to help the allergist/environmental physician integrate recommendations about improvements in outdoor and indoor air quality and the likely response to predicted alterations in the earth's environment into his or her patient's treatment plan. It incorporates references retrieved from Pub Med searches for topics, including:climate change, global warming, global climate change, greenhouse gasses, air pollution, particulates, black carbon, soot and sea level, as well as references contributed by the individual authors. Many changes that affect respiratory disease are anticipated.Examples of responses to climate change include energy reduction retrofits in homes that could potentially affect exposure to allergens and irritants, more hot sunny days that increase ozone-related difficulties, and rises in sea level or altered rainfall patterns that increase exposure to damp indoor environments.Climate changes can also affect ecosystems, manifested as the appearance of stinging and biting arthropods in new areas.Higher ambient carbon dioxide concentrations, warmer temperatures, and changes in floristic zones could potentially increase exposure to ragweed and other outdoor allergens,whereas green practices such as composting can increase allergen and irritant exposure. Finally, increased energy costs may resultin urban crowding and human source pollution, leading to changes in patterns of infectious respiratory illnesses. Improved governmental controls on airborne pollutants could lead to cleaner air and reduced respiratory diseases but will meet strong opposition because of their effect on business productivity. The allergy community must therefore adapt, as physician and research scientists always have, by anticipating the needs of patients and by adopting practices and research methods to meet changing environmental conditions.

[Male sterility and its association with genital disease and environmental factors].

PubMed

Merino Ruiz, M C; De León Cervantes, M G; García Flores, R F

1995-10-01

Semen quality may be affected by many factors, as there is evidence that conditions as varicocele, criptorquidia, orchitis and bacterian infections; as well as to exposure to physical agents as heat, or chemical substances, or ingestion of alcohol and drugs, may affect semen quality. The objective of this study is to investigate the risk implied in the exposure to these factors on the semen quality. The study was carried out in a prospective way in a group of males at Clínica de Infertilidad, Unidad de Biología de la Reproducción del Hospital Universitario Dr. J.E. González. Ninety nine males were studied, they received an intentioned questionnaire about antecedents of exposure to environmental factors, and urologic resolved pathology. Espermatobioscopy was done and it was classified according to OMS. Two groups were formed, one with the individuals with normal espermatobioscopy (n = 25); and the abnormal ones (n = 74). The statistical Incidences Reason, square Xi and Atributable Risk, were applied in order to determine the impact that different factors may have on semen quality. The found alterations in semen were astenozoospermia (n = 58); hypospermia (n = 22); oligozoospermia (n = 18); teratozoospermia (n = 7); polizoospermia (n = 7); and azoospermia (n = 6). The results of the mentioned statistical tests, show that in these alterations there is an associated risk factor to the use of tobacco, exposure to chemical substances, to physical aggresors; and anatomic anomalies previously corrected. It is considered that obtention of this information is a great help because once the unfavorable factors are eliminated, the environment is improved in order to obtain an espermatogenesis in optimal conditions.

Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

PubMed Central

Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.

2010-01-01

Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596

Global cytosine methylation in Daphnia magna depends on genotype, environment, and their interaction.

PubMed

Asselman, Jana; De Coninck, Dieter I M; Vandegehuchte, Michiel B; Jansen, Mieke; Decaestecker, Ellen; De Meester, Luc; Vanden Bussche, Julie; Vanhaecke, Lynn; Janssen, Colin R; De Schamphelaere, Karel A C

2015-05-01

The authors characterized global cytosine methylation levels in 2 different genotypes of the ecotoxicological model organism Daphnia magna after exposure to a wide array of biotic and abiotic environmental stressors. The present study aimed to improve the authors' understanding of the role of cytosine methylation in the organism's response to environmental conditions. The authors observed a significant genotype effect, an environment effect, and a genotype × environment effect. In particular, global cytosine methylation levels were significantly altered after exposure to Triops predation cues, Microcystis, and sodium chloride compared with control conditions. Significant differences between the 2 genotypes were observed when animals were exposed to Triops predation cues, Microcystis, Cryptomonas, and sodium chloride. Despite the low global methylation rate under control conditions (0.49-0.52%), global cytosine methylation levels upon exposure to Triops demonstrated a 5-fold difference between the genotypes (0.21% vs 1.02%). No effects were found in response to arsenic, cadmium, fish, lead, pH of 5.5, pH of 8, temperature, hypoxia, and white fat cell disease. The authors' results point to the potential role of epigenetic effects under changing environmental conditions such as predation (i.e., Triops), diet (i.e., Cryptomonas and Microcystis), and salinity. The results of the present study indicate that, despite global cytosine methylation levels being low, epigenetic effects may be important in environmental studies on Daphnia. © 2015 SETAC.

Dose assessment in environmental radiological protection: State of the art and perspectives.

PubMed

Stark, Karolina; Goméz-Ros, José M; Vives I Batlle, Jordi; Lindbo Hansen, Elisabeth; Beaugelin-Seiller, Karine; Kapustka, Lawrence A; Wood, Michael D; Bradshaw, Clare; Real, Almudena; McGuire, Corynne; Hinton, Thomas G

2017-09-01

Exposure to radiation is a potential hazard to humans and the environment. The Fukushima accident reminded the world of the importance of a reliable risk management system that incorporates the dose received from radiation exposures. The dose to humans from exposure to radiation can be quantified using a well-defined system; its environmental equivalent, however, is still in a developmental state. Additionally, the results of several papers published over the last decade have been criticized because of poor dosimetry. Therefore, a workshop on environmental dosimetry was organized by the STAR (Strategy for Allied Radioecology) Network of Excellence to review the state of the art in environmental dosimetry and prioritize areas of methodological and guidance development. Herein, we report the key findings from that international workshop, summarise parameters that affect the dose animals and plants receive when exposed to radiation, and identify further research needs. Current dosimetry practices for determining environmental protection are based on simple screening dose assessments using knowledge of fundamental radiation physics, source-target geometry relationships, the influence of organism shape and size, and knowledge of how radionuclide distributions in the body and in the soil profile alter dose. In screening model calculations that estimate whole-body dose to biota the shapes of organisms are simply represented as ellipsoids, while recently developed complex voxel phantom models allow organ-specific dose estimates. We identified several research and guidance development priorities for dosimetry. For external exposures, the uncertainty in dose estimates due to spatially heterogeneous distributions of radionuclide contamination is currently being evaluated. Guidance is needed on the level of dosimetry that is required when screening benchmarks are exceeded and how to report exposure in dose-effect studies, including quantification of uncertainties. Further research is needed to establish whether and how dosimetry should account for differences in tissue physiology, organism life stages, seasonal variability (in ecology, physiology and radiation field), species life span, and the proportion of a population that is actually exposed. We contend that, although major advances have recently been made in environmental radiation protection, substantive improvements are required to reduce uncertainties and increase the reliability of environmental dosimetry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells

PubMed Central

Brieño-Enríquez, Miguel A.; García-López, Jesús; Cárdenas, David B.; Guibert, Sylvain; Cleroux, Elouan; Děd, Lukas; Hourcade, Juan de Dios; Pěknicová, Jana; Weber, Michael; del Mazo, Jesús

2015-01-01

In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation. PMID:25897752

Shape memory polymer sensors for tracking cumulative environmental exposure

NASA Astrophysics Data System (ADS)

Snyder, Ryan; Rauscher, Michael; Vining, Ben; Havens, Ernie; Havens, Teresa; McFerran, Jace

2010-04-01

Cornerstone Research Group Inc. (CRG) has developed environmental exposure tracking (EET) sensors using shape memory polymers (SMP) to monitor the degradation of perishable items, such as munitions, foods and beverages, or medicines, by measuring the cumulative exposure to temperature and moisture. SMPs are polymers whose qualities have been altered to give them dynamic shape "memory" properties. Under thermal or moisture stimuli, the SMP exhibits a radical change from a rigid thermoset to a highly flexible, elastomeric state. The dynamic response of the SMP can be tailored to match the degradation profile of the perishable item. SMP-based EET sensors require no digital memory or internal power supply and provide the capability of inexpensive, long-term life cycle monitoring of thermal and moisture exposure over time. This technology was developed through Phase I and Phase II SBIR efforts with the Navy. The emphasis of current research centers on transitioning SMP materials from the lab bench to a production environment. Here, CRG presents the commercialization progress of thermally-activated EET sensors, focusing on fabrication scale-up, process refinements, and quality control. In addition, progress on the development of vapor pressure-responsive SMP (VPR-SMP) will be discussed.

Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA.

PubMed

Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

2017-10-01

To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of dietary crude oil exposure on molecular and physiological parameters related to lipid homeostasis in polar cod (Boreogadus saida).

PubMed

Vieweg, Ireen; Bilbao, Eider; Meador, James P; Cancio, Ibon; Bender, Morgan Lizabeth; Cajaraville, Miren P; Nahrgang, Jasmine

2018-04-01

Polar cod is an abundant Arctic key species, inhabiting an ecosystem that is subjected to rapid climate change and increased petroleum related activities. Few studies have investigated biological effects of crude oil on lipid metabolism in this species, despite lipids being a crucial compound for Arctic species to adapt to the high seasonality in food abundance in their habitat. This study examines the effects of dietary crude oil exposure on transcription levels of genes related to lipid metabolism (peroxisome proliferator-activated receptors [ppar-α, ppar-γ], retinoic X receptor [rxr-β], palmitoyl-CoA oxidase [aox1], cytochrome P4507A1 [cyp7α1]), reproduction (vitellogenin [vtg-β], gonad aromatase [cyp19a1]) and biotransformation (cytochrome P4501A1 [cyp1a1], aryl hydrocarbon receptor [ahr2]). Exposure effects were also examined through plasma chemistry parameters. Additional fish were exposed to a PPAR-α agonist (WY-14,643) to investigate the role of PPAR-α in their lipid metabolism. The dose-dependent up-regulation of cyp1a1 reflected the activation of genes related to PAH biotransformation upon crude oil exposure. The crude oil exposure did not significantly alter the mRNA expression of genes involved in lipid homeostasis except for cyp7α1 transcription levels. Plasma levels of cholesterol and alanine transaminase showed significant alterations in fish exposed to crude oil at the end of the experiment. WY exposure induced a down-regulation of ppar-α, an effect contrary to studies performed on other fish species. In conclusion, this study showed clear effects of dietary crude oil exposure at environmentally relevant concentrations on xenobiotic biotransformation but revealed only weak alterations in the lipid metabolism of polar cod. Copyright © 2018 Elsevier Inc. All rights reserved.

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice

PubMed Central

Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C.; Xi, Chuanwu

2016-01-01

Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in Avy strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. PMID:26962054

Mitochondrial Redox Dysfunction and Environmental Exposures

PubMed Central

Caito, Samuel W.

2015-01-01

Abstract Significance: Mitochondria are structurally and biochemically diverse, even within a single type of cell. Protein complexes localized to the inner mitochondrial membrane synthesize ATP by coupling electron transport and oxidative phosphorylation. The organelles produce reactive oxygen species (ROS) from mitochondrial oxygen and ROS can, in turn, alter the function and expression of proteins used for aerobic respiration by post-translational and transcriptional regulation. Recent Advances: New interest is emerging not only into the roles of mitochondria in disease development and progression but also as a target for environmental toxicants. Critical Issues: Dysregulation of respiration has been linked to cell death and is a major contributor to acute neuronal trauma, peripheral diseases, as well as chronic neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Future Directions: Here, we discuss the mechanisms underlying the sensitivity of the mitochondrial respiratory complexes to redox modulation, as well as examine the effects of environmental contaminants that have well-characterized mitochondrial toxicity. The contaminants discussed in this review are some of the most prevalent and potent environmental contaminants that have been linked to neurological dysfunction, altered cellular respiration, and oxidation. Antioxid. Redox Signal. 23, 578–595. PMID:25826672

Low impact of exposure to environmentally relevant doses of 226Ra in Atlantic cod (Gadus morhua) embryonic cells.

PubMed

Olsvik, Pål A; Berntssen, Marc H G; Hylland, Ketil; Eriksen, Dag Ø; Holen, Elisabeth

2012-07-01

The aim of this study was to investigate whether (226)Ra, a radionuclide present in produced water from oil platforms in the North Sea and other offshore drilling areas, could affect vulnerable early life stages of Atlantic cod (Gadus morhua). Blastula-stage embryonic cells (EC) from fertilized eggs of Atlantic cod were isolated and exposed to environmental relevant concentrations of (226)Ra and transcription of selected genes quantified. The results showed a weak, but significant up-regulation of GPx3 and HSP70 transcripts after 48 h of exposure to 2.11 Bq/L. In EC exposed to three (226)Ra concentrations (2.11, 23 and 117 Bq/L) for 12 h, metallothionein, HSP90AA, thioredoxin and caspase 8 were significantly up-regulated in cells exposed to 117 Bq/L, whereas thioredoxin was also significantly up-regulated in EC exposed to 23 Bq/L. When EC were exposed to the same (226)Ra concentrations for 48 h, only heme oxygenase was significantly up-regulated in the 23 Bq/L exposure group. The results suggest that environmentally relevant activities of (226)Ra may induce oxidative stress and apoptosis in fish ECs. Exposure of Atlantic cod EC to Cd, selected as a model toxicant, supported the ability of EC around blastula stage to respond to toxicants by altered transcription. Due to dilution, environmentally relevant concentrations of radionuclides present in produced water would be expected to pose a minor threat to early life stages of fish. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease.

PubMed

Skinner, Michael K; Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; Nilsson, Eric; McBirney, Margaux; Klukovich, Rachel; Xie, Yeming; Tang, Chong; Yan, Wei

2018-02-27

Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated. DNA methylation and ncRNA were altered in each generation sperm with the direct exposure F1 and F2 generations being predominantly distinct from the F3 generation epimutations. The piRNA and small tRNA were the most predominant classes of ncRNA altered. A highly conserved set of histone retention sites were found in the control lineage generations which was not significantly altered between generations, but a large number of new histone retention sites were found only in the transgenerational generation DDT lineage sperm. Therefore, all three different epigenetic processes were concurrently altered as DDT induced the epigenetic transgenerational inheritance of sperm epimutations. The direct exposure generations sperm epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene associations with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Observations demonstrate all three epigenetic processes are involved in transgenerational inheritance. The different epigenetic processes appear to be integrated in mediating the epigenetic transgenerational inheritance phenomenon.

An experimental heat wave changes immune defense and life history traits in a freshwater snail.

PubMed

Leicht, Katja; Jokela, Jukka; Seppälä, Otto

2013-12-01

The predicted increase in frequency and severity of heat waves due to climate change is expected to alter disease dynamics by reducing hosts' ability to resist infections. This could take place via two different mechanisms: (1) through general reduction in hosts' performance under harsh environmental conditions and/or (2) through altered resource allocation that reduces expression of defense traits in order to maintain other traits. We tested these alternative hypotheses by measuring the effect of an experimental heat wave (25 vs. 15°C) on the constitutive level of immune defense (hemocyte concentration, phenoloxidase [PO]-like activity, antibacterial activity of hemolymph), and life history traits (growth and number of oviposited eggs) of the great pond snail Lymnaea stagnalis. We also manipulated the exposure time to high temperature (1, 3, 5, 7, 9, or 11 days). We found that if the exposure to high temperature lasted <1 week, immune function was not affected. However, when the exposure lasted longer than that, the level of snails' immune function (hemocyte concentration and PO-like activity) was reduced. Snails' growth and reproduction increased within the first week of exposure to high temperature. However, longer exposures did not lead to a further increase in cumulative reproductive output. Our results show that short experimental heat waves do not alter immune function but lead to plastic responses that increase snails' growth and reproduction. Thus, although the relative expression of traits changes, short experimental heat waves do not impair snails' defenses. Negative effects on performance get pronounced when the heat waves are prolonged suggesting that high performance cannot be maintained over long time periods. This ultimately reduces the levels of defense traits.

Gestational exposure to inorganic arsenic (iAs3+) alters glutamate disposition in the mouse hippocampus and ionotropic glutamate receptor expression leading to memory impairment.

PubMed

Nelson-Mora, Janikua; Escobar, Martha L; Rodríguez-Durán, Luis; Massieu, Lourdes; Montiel, Teresa; Rodríguez, Verónica M; Hernández-Mercado, Karina; Gonsebatt, María E

2018-03-01

Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes. Here, we used the same gestational iAs exposure model to investigate whether the up-regulation of xCT and down-regulation of GLT-1 transporters were associated with higher levels of extracellular glutamate and changes in the expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor, responsible for excitatory fast synaptic transmission. The induction of LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also studied, as well as learning and memory formation using the water maze test. Changes in GSH levels were also tested in the hippocampus of animals exposed to iAs. Results showed increased GSH synthesis (p < 0.05), associated with significantly higher extracellular glutamate levels in iAs exposed mice. Exposure was also significantly associated with AMPA subunits down-regulation, deficient LTP induction, and lower excitability of the PP-DG pathway. In addition, animals showed deficient learning and memory in the Morris Water Maze test.

Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis.

PubMed

DeLuca, Jennifer Aa; Allred, Kimberly F; Menon, Rani; Riordan, Rebekah; Weeks, Brad R; Jayaraman, Arul; Allred, Clinton D

2018-06-01

Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut microbiome and the metabolites they produce. This study is the first to show that bisphenol-A alone alters tryptophan and microbiota metabolites derived from aromatic amino acids in a manner consistent with autoimmune diseases, specifically inflammatory bowel diseases, regardless of dextran sulfate sodium treatment. These findings indicate a potential mechanism by which bisphenol-A negatively affects gut physiology to exacerbate inflammation.

The epigenetic lorax: gene–environment interactions in human health

PubMed Central

Latham, Keith E; Sapienza, Carmen; Engel, Nora

2012-01-01

Over the last decade, we have witnessed an explosion of information on genetic factors underlying common human diseases and disorders. This ‘human genomics’ information revolution has occurred as a backdrop to a rapid increase in the rates of many human disorders and diseases. For example, obesity, Type 2 diabetes, asthma, autism spectrum disorder and attention deficit hyperactivity disorder have increased at rates that cannot be due to changes in the genetic structure of the population, and are difficult to ascribe to changes in diagnostic criteria or ascertainment. A likely cause of the increased incidence of these disorders is increased exposure to environmental factors that modify gene function. Many environmental factors that have epidemiological association with common human disorders are likely to exert their effects through epigenetic alterations. This general mechanism of gene–environment interaction poses special challenges for individuals, educators, scientists and public policy makers in defining, monitoring and mitigating exposures. PMID:22920179

Gene-Chemical Interactions in the Developing Mammalian Nervous System: Effects on Proliferation, Neurogenesis and Differentiation

PubMed Central

Fox, Donald A.; Opanashuk, Lisa; Zharkovsky, Aleksander; Weiss, Bernie

2010-01-01

The orderly formation of the nervous system requires a multitude of complex, integrated and simultaneously occurring processes. Neural progenitor cells expand through proliferation, commit to different cell fates, exit the cell cycle, generate different neuronal and glial cell types, and new neurons migrate to specified areas and establish synaptic connections. Gestational and perinatal exposure to environmental toxicants, pharmacological agents and drugs of abuse produce immediate, persistent or late-onset alterations in behavioral, cognitive, sensory and/or motor functions. These alterations reflect the disruption of the underlying processes of CNS formation and development. To determine the neurotoxic mechanisms that underlie these deficits it is necessary to analyze and dissect the complex molecular processes that occur during the proliferation, neurogenesis and differentiation of cells. This symposium will provide a framework for understanding the orchestrated events of neurogenesis, the coordination of proliferation and cell fate specification by selected genes, and the effects of well-known neurotoxicants on neurogenesis in the retina, hippocampus and cerebellum. These three tissues share common developmental profiles, mediate diverse neuronal activities and function, and thus provide important substrates for analysis. This paper summarizes four invited talks that were presented at the 12th International Neurotoxicology Association meeting held in Jerusalem, Israel during the summer of 2009. Donald A. Fox described the structural and functional alterations following low-level gestational lead exposure in children and rodents that produced a supernormal electroretinogram and selective increases in neurogenesis and cell proliferation of late-born retinal neurons (rod photoreceptors and bipolar cells), but not Müller glia cells, in mice. Lisa Opanashuk discussed how dioxin [TCDD] binding to the arylhydrocarbon receptor [AhR], a transcription factor that regulates xenobiotic metabolizing enzymes and growth factors, increased granule cell formation and apoptosis in the developing mouse cerebellum. Alex Zharkovsky described how postnatal early postnatal lead exposure decreased cell proliferation, neurogenesis and gene expression in the dentate gyrus of the adult hippocampus and its resultant behavioral effects. Bernard Weiss illustrated how environmental endocrine disruptors produced age- and gender-dependent alterations in synaptogenesis and cognitive behavior. PMID:20381523

Effects of glyphosate-based herbicides on survival, development and growth of invasive snail (Pomacea canaliculata).

PubMed

Xu, Yanggui; Li, Adela Jing; Li, Kaibin; Qin, Junhao; Li, Huashou

2017-12-01

This study tests the hypotheses that whether environmental relevance of glyphosate would help control spread of the invasive snail Pomacea canaliculata, or benefit its population growth worldwide. Our results showed that glyphosate induced acute toxicity to the snail only at high concentrations (96h LC50 at 175mg/L) unlikely to occur in the environment. Long-term exposures to glyphosate at sublethal levels (20 and 120mg/L) caused inhibition of food intake, limitation of growth performance and alterations in metabolic profiles of the snail. It is worth noting that glyphosate at 2mg/L benefited growth performance in P. canaliculata. Chronic exposures of glyphosate significantly enhanced overall metabolic rate and altered catabolism from protein to carbohydrate/lipid mode. Cellular responses in enzyme activities showed that the exposed snails could increase tolerance by their defense system against glyphosate-induced oxidative stress, and adjustment of metabolism to mitigate energy crisis. Our study displayed that sublethal concentrations of glyphosate might be helpful in control of the invasive species by food intake, growth performance and metabolic interruption; whether environmental relevance of glyphosate (≤2mg/L) benefits population growth of P. canaliculata is still inconclusive, which requires further field study. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway

PubMed Central

Rager, Julia E.; Yosim, Andrew; Fry, Rebecca C.

2014-01-01

There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans. PMID:25479081

Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC).

PubMed

Song, Mi-Kyung; Ryu, Jae-Chun

2015-10-01

To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs. Copyright © 2015 Elsevier GmbH. All rights reserved.

The effects of ozone exposure and associated injury mechanisms on the central nervous system.

PubMed

Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María; Franco-Pérez, Javier; Custodio, Verónica; Hernández-Cerón, Miguel; Livera, Carlos; Paz, Carlos

2013-01-01

Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

Environmental History Modulates Arabidopsis Pattern-Triggered Immunity in a HISTONE ACETYLTRANSFERASE1-Dependent Manner.

PubMed

Singh, Prashant; Yekondi, Shweta; Chen, Po-Wen; Tsai, Chia-Hong; Yu, Chun-Wei; Wu, Keqiang; Zimmerli, Laurent

2014-06-01

In nature, plants are exposed to a fluctuating environment, and individuals exposed to contrasting environmental factors develop different environmental histories. Whether different environmental histories alter plant responses to a current stress remains elusive. Here, we show that environmental history modulates the plant response to microbial pathogens. Arabidopsis thaliana plants exposed to repetitive heat, cold, or salt stress were more resistant to virulent bacteria than Arabidopsis grown in a more stable environment. By contrast, long-term exposure to heat, cold, or exposure to high concentrations of NaCl did not provide enhanced protection against bacteria. Enhanced resistance occurred with priming of Arabidopsis pattern-triggered immunity (PTI)-responsive genes and the potentiation of PTI-mediated callose deposition. In repetitively stress-challenged Arabidopsis, PTI-responsive genes showed enrichment for epigenetic marks associated with transcriptional activation. Upon bacterial infection, enrichment of RNA polymerase II at primed PTI marker genes was observed in environmentally challenged Arabidopsis. Finally, repetitively stress-challenged histone acetyltransferase1-1 (hac1-1) mutants failed to demonstrate enhanced resistance to bacteria, priming of PTI, and increased open chromatin states. These findings reveal that environmental history shapes the plant response to bacteria through the development of a HAC1-dependent epigenetic mark characteristic of a primed PTI response, demonstrating a mechanistic link between the primed state in plants and epigenetics. © 2014 American Society of Plant Biologists. All rights reserved.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

USGS Publications Warehouse

Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

2017-01-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations.

PubMed

Dautel, Franziska; Kalkhof, Stefan; Trump, Saskia; Michaelson, Jacob; Beyer, Andreas; Lehmann, Irina; von Bergen, Martin

2011-02-04

Although the effects of high concentrations of the carcinogen benzo[a]pyrene (B[a]P) have been studied extensively, little is known about its effects at subacute toxic concentrations, which are typical for environmental pollutants. We exposed murine Hepa1c1c7 cells to a toxic concentration (5 μM) and a subacute concentration (50 nM) of B[a]P over a period of 2-24 h to differentiate between acute and pseudochronic effects and conducted a time-course analysis of B[a]P-influenced protein expression by DIGE. In total, a set of 120 spots were found to be significantly altered due to B[a]P exposure of which 112 were subsequently identified by mass spectrometry. Clustering and principal component analysis were conducted to identify sets of proteins responding in a concerted manner to the exposure. Our results indicate an immediate response to the contaminant at the protein level and demonstrate that B[a]P exposure alters the cellular response by disturbing proteins involved in oxidative stress, cell cycle regulation, apoptosis, and cytoskeleton organization. Furthermore, network analysis of protein-protein interactions revealed a complex network of interacting, B[a]P-regulated proteins mostly belonging to the cytoskeleton organization and several signal transduction pathways.

The effect of lead exposure on fatty acid composition in mouse brain analyzed using pseudo-catalytic derivatization.

PubMed

Jung, Jong-Min; Lee, Jechan; Kim, Ki-Hyun; Jang, In Geon; Song, Jae Gwang; Kang, Kyeongjin; Tack, Filip M G; Oh, Jeong-Ik; Kwon, Eilhann E; Kim, Hyung-Wook

2017-03-01

We performed toxicological study of mice exposed to lead by quantifying fatty acids in brain of the mice. This study suggests that the introduced analytical method had an extremely high tolerance against impurities such as water and extractives; thus, it led to the enhanced resolution in visualizing the spectrum of fatty acid profiles in animal brain. Furthermore, one of the biggest technical advantages achieved in this study was the quantitation of fatty acid methyl ester profiles of mouse brain using a trace amount of sample (e.g., 100 μL mixture). Methanol was screened as the most effective extraction solvent for mouse brain. The behavioral test of the mice before and after lead exposure was conducted to see the effect of lead exposure on fatty acid composition of the mice' brain. The lead exposure led to changes in disease-related behavior of the mice. Also, the lead exposure induced significant alterations of fatty acid profile (C16:0, C 18:0, and C 18:1) in brain of the mice, implicated in pathology of psychiatric diseases. The alteration of fatty acid profile of brain of the mice suggests that the derivatizing technique can be applicable to most research fields associated with the environmental neurotoxins with better resolution in a short time, as compared to the current protocols for lipid analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

PubMed Central

Vallaster, Markus P; Kukreja, Shweta; Bing, Xin Y; Ngolab, Jennifer; Zhao-Shea, Rubing; Gardner, Paul D; Tapper, Andrew R; Rando, Oliver J

2017-01-01

Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal ‘quality of life’. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics. DOI: http://dx.doi.org/10.7554/eLife.24771.001 PMID:28196335

Systematic review of biological effects of exposure to static electric fields. Part II: Invertebrates and plants.

PubMed

Schmiedchen, Kristina; Petri, Anne-Kathrin; Driessen, Sarah; Bailey, William H

2018-01-01

The construction of high-voltage direct current (HVDC) lines for the long-distance transport of energy is becoming increasingly popular. This has raised public concern about potential environmental impacts of the static electric fields (EF) produced under and near HVDC power lines. As the second part of a comprehensive literature analysis, the aim of this systematic review was to assess the effects of static EF exposure on biological functions in invertebrates and plants and to provide the basis for an environmental impact assessment of such exposures. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to guide the methodological conduct and reporting. Thirty-three studies - 14 invertebrate and 19 plant studies - met the eligibility criteria and were included in this review. The reported behavioral responses of insects and planarians upon exposure strongly suggest that invertebrates are able to perceive the presence of a static EF. Many other studies reported effects on physiological functions that were expressed as, for example, altered metabolic activity or delayed reproductive and developmental stages in invertebrates. In plants, leaf damage, alterations in germination rates, growth and yield, or variations in the concentration of essential elements, for example, have been reported. However, these physiological responses and changes in plant morphology appear to be secondary to surface stimulation by the static EF or caused by concomitant parameters of the electrostatic environment. Furthermore, all of the included studies suffered from methodological flaws, which lowered credibility in the results. At field levels encountered from natural sources or HVDC lines (< 35kV/m), the available data provide reliable evidence that static EF can trigger behavioral responses in invertebrates, but they do not provide evidence for adverse effects of static EF on other biological functions in invertebrates and plants. At far higher field levels (> 35kV/m), adverse effects on physiology and morphology, presumably caused by corona-action, appear to be more likely. Higher quality studies are needed to unravel the role of air ions, ozone, nitric oxide and corona current on alterations in physiological functions and morphology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Potential impact of acid precipitation on arsenic and selenium.

PubMed Central

Mushak, P

1985-01-01

The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling. PMID:4076075

Potential impact of acid precipitation on arsenic and selenium.

PubMed

Mushak, P

1985-11-01

The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling.

Response of transposable elements to environmental stressors.

PubMed

Miousse, Isabelle R; Chalbot, Marie-Cecile G; Lumen, Annie; Ferguson, Alesia; Kavouras, Ilias G; Koturbash, Igor

2015-01-01

Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as "junk DNA," TEs are now well-accepted driving forces of evolution and critical regulators of the expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention. Copyright © 2015 Elsevier B.V. All rights reserved.

Transposable elements in response to environmental stressors&

PubMed Central

Miousse, Isabelle R.; Chalbot, Marie-Cecile G.; Lumen, Annie; Ferguson, Alesia; Kavouras, Ilias G.; Koturbash, Igor

2015-01-01

Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as “junk DNA,” TEs are now well-accepted driving forces of evolution and critical regulators the of expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention. PMID:26281766

Development of gypsum alteration on marble and limestone

USGS Publications Warehouse

McGee, E.S.

1996-01-01

Blackened alteration crusts of gypsum plus particulates that form on sheltered areas on marble and limestone buildings pose a challenge for rehabilitation and cleaning. Fresh marble and limestone samples exposed at monitored exposure sites present conditions of simple geometry and well-documented exposures but have short exposure histories (one to five years). The gypsum alteration crusts that develop on these samples provide insight into the early stages and rate of alteration crust formation. Alteration crusts from buildings give a longer, but less well known exposure history and present much more complex surfaces for gypsum accumulation. Integrated observations and measurements of alteration crusts from exposure samples and from buildings identify four factors that are important in the formation and development of alteration crusts on marble and limestone: (1) pollution levels, (2) exposure to rain or washing, (3) geometry of exposure of the stone surface, and (4) permeability of the stone. The combination of these factors contributes to both the distribution and the physical characteristics of the gypsum crusts which may affect cleaning decisions.

Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.

PubMed

Grippo, Angela J; Moffitt, Julia A; Henry, Matthew K; Firkins, Rachel; Senkler, Jonathan; McNeal, Neal; Wardwell, Joshua; Scotti, Melissa-Ann L; Dotson, Ashley; Schultz, Rachel

2015-01-01

Exposure to social and environmental stressors may influence behavior as well as autonomic and cardiovascular regulation, potentially leading to depressive disorders and cardiac dysfunction including elevated sympathetic drive, reduced parasympathetic function, and ventricular arrhythmias. The cellular mechanisms that underlie these interactions are not well understood. One mechanism may involve alterations in the expression of Connexin43 (Cx43) and Connexin45 (Cx45), gap junction proteins in the heart that play an important role in ensuring efficient cell-to-cell coupling and the maintenance of cardiac rhythmicity. The present study investigated the hypothesis that long-term social isolation, combined with mild environmental stressors, would produce both depressive behaviors and altered Cx43 and Cx45 expression in the left ventricle of prairie voles - a socially monogamous rodent model. Adult, female prairie voles were exposed to either social isolation (n = 22) or control (paired, n = 23) conditions (4 weeks), alone or in combination with chronic mild stress (CMS) (1 week). Social isolation, versus paired control conditions, produced significantly (p < 0.05) increased depressive behaviors in a 5-min forced swim test, and CMS exacerbated (p < 0.05) these behaviors. Social isolation (alone) reduced (p < 0.05) total Cx43 expression in the left ventricle; whereas CMS (but not isolation) increased (p < 0.05) total Cx45 expression and reduced (p < 0.05) the Cx43/Cx45 ratio, measured via Western blot analysis. The present findings provide insight into potential cellular mechanisms underlying altered cardiac rhythmicity associated with social and environmental stress in the prairie vole.

Sensitivity of coral recruitment to subtle shifts in early community succession.

PubMed

Doropoulos, Christopher; Roff, George; Visser, Mart-Simone; Mumby, Peter J

2017-02-01

Community succession following disturbance depends on positive and negative interactions, the strength of which change along environmental gradients. To investigate how early succession affects coral reef recovery, we conducted an 18-month experiment in Palau, using recruitment tiles and herbivore exclusion cages. One set of reefs has higher wave exposure and had previously undergone a phase shift to macroalgae following a major typhoon, whereas the other set of reefs have lower wave exposure and did not undergo a macroalgal phase shift. Similar successional trajectories were observed at all sites when herbivores were excluded: turf algae dominated early succession, followed by shifts to foliose macroalgae and heterotrophic invertebrates. However, trajectories differed in the presence of herbivores. At low wave exposure reefs, herbivores promoted coralline algae and limited turf and encrusting fleshy algae in crevice microhabitats, facilitating optimal coral recruitment. Under medium wave exposure, relatively higher but still low coverage of turf and encrusting fleshy algae (15-25%) found in crevice microhabitats inhibited coral recruitment, persisting throughout multiple recruitment events. Our results indicate that altered interaction strength in different wave environments following disturbance can drive subtle changes in early succession that cascade to alter secondary succession to coral recruitment and system recovery. © 2016 by the Ecological Society of America.

Immunological and physiological effects of chronic exposure of Peromyscus leucopus to Aroclor 1254 at a concentration similar to that found at contaminated sites

USGS Publications Warehouse

Segre, M.; Arena, S.M.; Greeley, E.H.; Melancon, M.J.; Graham, D.A.; French, J.B.

2002-01-01

Polychlorinated biphenyls (PCBs) are environmental contaminants known to cause adverse health effects to biological systems. Limited data are available on their effects on the immune system of wildlife species. Previously, we found that 4 and 6-week-old white-footed mice (Peromyscus leucopus) born from dams injected with a single dose (300 mg/kg) of Aroclor 1254, had altered immunological, hematological, and biochemical responses. Here, we examined the effect of transplacental lactational and postnatal exposure to Aroclor 1254, at a concentration similar to that found at contaminated sites, on various physiological parameters of 22-week-old white-footed mice. Liver weight and liver somatic index of PCB treated animals were significantly higher, the combined weights of the adrenal glands were significantly lower and EROD and BROD enzyme activity was significantly higher compared to control values. The number of thymocytes of the treated mice was significantly lower than that of the controls; however, thymocytes of treated mice had a higher proliferative response to the mitogen Con A. These alterations were correlated with the PCBs body burdens. Some toxic effects of chronic exposure to PCBs, at levels comparable to exposure found in contaminated sites in the USA, are still evident in adult P. leucopus.

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

PubMed Central

Gilleron, Jérôme; Carette, Diane; Segretain, Dominique

2011-01-01

Many recent epidemiological, clinical and experimental findings support the hypothesis that environmental toxicants are responsible for the increasing male reproductive disorders (congenital malformations, declining sperm counts and testicular cancer) over the past 20 years. It has also been reported that exposure to these toxicants, during critical periods of development (fetal and neonatal), represents a more considerable risk for animals and humans than exposure during adulthood. However, the molecular targets for these chemicals have not been clearly identified. Recent studies showed that a family of transmembranous proteins, named connexins, regulates numerous physiological processes involved in testicular development and function, such as Sertoli and germ cell proliferation, differentiation, germ cell migration and apoptosis. In the testis, knockout strategy revealed that connexin 43, the predominant connexin in this organ, is essential for spermatogenesis. In addition, there is evidence that many environmental toxicants could alter testicular connexin 43 by dysregulation of numerous mechanisms controlling its function. In the present work, we propose first to give an overview of connexin expression and intercellular gap junction coupling in the developing fetal and neonatal testes. Second, we underline the impact of maternally chemical exposure on connexin 43 expression in the perinatal developing testis. Lastly, we attempt to link this precocious effect to male offspring fertility. PMID:22332114

Hepatic Proteome Analysis of Atlantic Salmon (Salmo salar) After Exposure to Environmental Concentrations of Human Pharmaceuticals*

PubMed Central

Hampel, Miriam; Alonso, Esteban; Aparicio, Irene; Santos, Juan Luis; Leaver, Michael

2015-01-01

Pharmaceuticals are pseudopersistent aquatic pollutants with unknown effects at environmentally relevant concentrations. Atlantic salmon (Salmo salar) were exposed to Acetaminophen: 54.77 ± 34.67; Atenolol: 11.08 ± 7.98, and Carbamazepine: 7.85 ± 0.13 μg·L−1 for 5 days. After Acetaminophen treatment, 19 proteins were differently expressed, of which 11 were significant with respect to the control group (eight up-regulated and three down-regulated). After Atenolol treatment, seven differently expressed proteins were obtained in comparison with the control, of which six could be identified (four up-regulated and two down-regulated). Carbamazepine exposure resulted in 15 differently expressed proteins compared with the control, with 10 of them identified (seven up-regulated and three down-regulated). Out of these, three features were common between Acetaminophen and Carbamazepine and one between Carbamazepine and Atenolol. One feature was common across all treatments. Principal component analysis and heat map clustering showed a clear grouping of the variability caused by the applied treatments. The obtained data suggest (1) that exposure to environmentally relevant concentrations of the pharmaceuticals alters the hepatic protein expression profile of the Atlantic salmon; and (2) the existence of treatment specific processes that may be useful for biomarker development. PMID:25394398

Physiological responses and gene expression changes in the western mosquitofish (Gambusia affinis) exposed to progesterone at environmentally relevant concentrations.

PubMed

Hou, Liping; Xu, Hongyan; Ying, Guangguo; Yang, Yang; Shu, Hu; Zhao, Jianliang; Cheng, Xuemei

2017-11-01

Progesterone (P4) is a natural and synthetic steroid, widely distributed in the aquatic environments. It can lead to adverse effects on the endocrine system in aquatic organisms. This study investigated the toxicological effects of exposure to environmentally relevant concentrations (4, 44, and 410ng/L) of progesterone for 42 d on adult female mosquitofish, Gambusia affinis. We performed morphological and histological analyses on gonads, anal fins, liver, and gills after the exposure of mosquito fish to P4. The expression levels of genes (vtg, er, and ar isoforms) related to fish reproduction and detoxification (cyp1a) in the liver were quantified by quantitative real-time polymerase chain reaction. The results showed that the progesterone exposure induced slight masculinization in female mosquitofish, influenced the oocyte maturation as revealed by histology of the ovaries, and caused severe damages to the liver and gills of adult female mosquitofish. It also suppressed the mRNAs expression of vtg, er, cyp1a, and significantly enhanced the expression of ar mRNA in the liver. This study reveals the molecular and physiological effects of progesterone at environmentally relevant concentrations, which might further be translated to alterations in the reproduction of mosquitofish. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

PubMed

Roy, Anirban; Bauer, Stephen M; Lawrence, B Paige

2012-01-01

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice.

PubMed

Rubin, Beverly S; Paranjpe, Maneesha; DaFonte, Tracey; Schaeberle, Cheryl; Soto, Ana M; Obin, Martin; Greenberg, Andrew S

2017-03-01

Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and adiposity, and to assess potential sex differences in this response. Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition. The effects were dose specific and sex specific and were influenced by the precise window of BPA exposure. The addition of peripubertal BPA exposure following the initial perinatal exposure exacerbated adverse effects in the females but appeared to reduce differences in body weight and body composition between control and BPA exposed males. Some effects of BPA on body weight and body composition showed a non-linear dose response. Copyright © 2016. Published by Elsevier Inc.

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

PubMed

Cheung, Ivy N; Zee, Phyllis C; Shalman, Dov; Malkani, Roneil G; Kang, Joseph; Reid, Kathryn J

2016-01-01

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.

The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression.

PubMed

Winterbottom, Emily F; Koestler, Devin C; Fei, Dennis Liang; Wika, Eric; Capobianco, Anthony J; Marsit, Carmen J; Karagas, Margaret R; Robbins, David J

2017-06-14

Sex-specific factors play a major role in human health and disease, including responses to environmental stresses such as toxicant exposure. Increasing evidence suggests that such sex differences also exist during fetal development. In a previous report using the resources of the New Hampshire Birth Cohort Study (NHBCS), we found that low-to-moderate in utero exposure to arsenic, a highly toxic and widespread pollutant, was associated with altered expression of several key developmental genes in the fetal portion of the placenta. These associations were sex-dependent, suggesting that in utero arsenic exposure differentially impacts male and female fetuses. In the present study, we investigated the molecular basis for these sex-specific responses to arsenic. Using NanoString technology, we further analyzed the fetal placenta samples from the NHBCS for the expression of genes encoding arsenic transporters and metabolic enzymes. Multivariable linear regression analysis was used to examine their relationship with arsenic exposure and with key developmental genes, after stratification by fetal sex. We found that maternal arsenic exposure was strongly associated with expression of the AQP9 gene, encoding an aquaglyceroporin transporter, in female but not male fetal placenta. Moreover, AQP9 expression associated with that of a subset of female-specific arsenic-responsive genes. Our results suggest that AQP9 is upregulated in response to arsenic exposure in female, but not male, fetal placenta. Based on these results and prior studies, increased AQP9 expression may lead to increased arsenic transport in the female fetal placenta, which in turn may alter the expression patterns of key developmental genes that we have previously shown to be associated with arsenic exposure. Thus, this study suggests that AQP9 may play a role in the sex-specific effects of in utero arsenic exposure.

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

PubMed Central

Cheung, Ivy N.; Zee, Phyllis C.; Shalman, Dov; Malkani, Roneil G.; Kang, Joseph; Reid, Kathryn J.

2016-01-01

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. PMID:27191727

Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

PubMed

Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

2018-05-01

Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Synergistic effects of ultraviolet radiation, thermal cycling and atomic oxygen on altered and coated Kapton surfaces

NASA Technical Reports Server (NTRS)

Dever, Joyce A.; Bruckner, Eric J.; Rodriguez, Elvin

1992-01-01

The photovoltaic (PV) power system for Space Station Freedom (SSF) uses solar array blankets which provide structural support for the solar cells and house the electrical interconnections. In the low earth orbital (LEO) environment where SSF will be located, surfaces will be exposed to potentially damaging environmental conditions including solar ultraviolet (UV) radiation, thermal cycling, and atomic oxygen. It is necessary to use ground based tests to determine how these environmental conditions would affect the mass loss and optical properties of candidate SSF blanket materials. Silicone containing, silicone coated, and SiO(x) coated polyimide film materials were exposed to simulated LEO environmental conditions to determine their durability and whether the environmental conditions of UV, thermal cycling and oxygen atoms act synergistically on these materials. A candidate PV blanket material called AOR Kapton, a polysiloxane polyimide cast from a solution mixture, shows an improvement in durability to oxygen atoms erosion after exposure to UV radiation or thermal cycling combined with UV radiation. This may indicate that the environmental conditions react synergistically with this material, and the damage predicted by exposure to atomic oxygen alone is more severe than that which would occur in LEO where atomic oxygen, thermal cycling and UV radiation are present together.

Synergistic effects of ultraviolet radiation, thermal cycling, and atomic oxygen on altered and coated Kapton surfaces

NASA Technical Reports Server (NTRS)

Dever, Joyce A.; Bruckner, Eric J.; Rodriguez, Elvin

1992-01-01

The photovoltaic (PV) power system for Space Station Freedom (SSF) uses solar array blankets which provide structural support for the solar cells and house the electrical interconnections. In the low Earth orbital (LEO) environment where SSF will be located, surfaces will be exposed to potentially damaging environmental conditions including solar ultraviolet (UV) radiation, thermal cycling, and atomic oxygen. It is necessary to use ground based tests to determine how these environmental conditions would affect the mass loss and optical properties of candidate SSF blanket materials. Silicone containing, silicone coated, and SiO(x) coated polyimide film materials were exposed to simulated LEO environmental conditions to determine there durability and whether the environmental conditions of UV, thermal cycling and oxygen atoms act synergistically on these materials. A candidate PV blanket material called AOR Kapton, a polysiloxane polyimide cast from a solution mixture, shows an improvement in durability to oxygen atoms erosion after exposure to UV radiation or thermal cycling combined with UV radiation. This may indicate that the environmental conditions react synergistically with this material, and the damage predicted by exposure to atomic oxygen alone is more severe than that which would occur in LEO where atomic oxygen, thermal cycling and UV radiation are present together.

Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio).

PubMed

DeBofsky, Abigail R; Klingler, Rebekah H; Mora-Zamorano, Francisco X; Walz, Marcus; Shepherd, Brian; Larson, Jeremy K; Anderson, David; Yang, Luobin; Goetz, Frederick; Basu, Niladri; Head, Jessica; Tonellato, Peter; Armstrong, Brandon M; Murphy, Cheryl; Carvan, Michael J

2018-03-01

The purpose of this study was to evaluate the effects of environmentally relevant dietary MeHg exposures on adult female yellow perch (Perca flavescens) and female zebrafish (Danio rerio) ovarian development and reproduction. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg following a whole life-cycle exposure. Chronic whole life dietary exposure of F 1 zebrafish to MeHg mimics realistic wildlife exposure scenarios, and the twenty-week adult yellow perch exposure (where whole life-cycle exposures are difficult) captures early seasonal ovarian development. For both species, target dietary accumulation values were achieved prior to analyses. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-sequencing and quantitative real-time polymerase chain reaction (QPCR), but no significant phenotypic changes were observed regarding ovarian staging, fecundity, or embryo mortality. Yellow perch were exposed to dietary MeHg for 12, 16, or 20 weeks. In this species, a set of eight genes were assessed by QPCR in the pituitary, liver, and ovary, and no exposure-related changes were observed. The lack of genomic resources in yellow perch hinders the characterization of subtle molecular impacts. The ovarian somatic index, circulating estradiol and testosterone, and ovarian staging were not significantly altered by MeHg exposure in yellow perch. These results suggest that environmentally relevant MeHg exposures do not drastically reduce the reproductively important endpoints in these fish, but to capture realistic exposure scenarios, whole life-cycle yellow perch exposures are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sources, mechanisms, and consequences of chemical-induced mitochondrial toxicity

PubMed Central

Meyer, Joel N.; Chan, Sherine S. L.

2017-01-01

Mitochondrial function is critical for health, as demonstrated by the effects of mitochondrial toxicity, mutations in genes encoding mitochondrial proteins, and the role of mitochondrial dysfunction in many chronic diseases. However, much basic mitochondrial biology is still being discovered. Furthermore, the details of how different environmental exposures affect mitochondria, how mitochondria respond to stressors, and how genetic variation affecting mitochondrial function alters response to exposures are areas of rapid research growth. This Special Issue was created to highlight and review cutting-edge areas of research into chemical effects on mitochondrial function. We anticipate that it will stimulate additional research into the mechanisms by which chemical exposures impact mitochondria, the biological processes that protect mitochondria from such impacts, and the health consequences that result when defense and homeostatic mechanisms are overcome. PMID:28627407

Prenatal stress and epigenetics.

PubMed

Cao-Lei, L; de Rooij, S R; King, S; Matthews, S G; Metz, G A S; Roseboom, T J; Szyf, M

2017-05-18

In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations. We also emphasized the advantage of using stressor from quasi-randomly assigned experiments. Furthermore, we discuss challenges that still need to be addressed in this field in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Environmentally relevant concentrations of citalopram partially inhibit feeding in the three-spine stickleback (Gasterosteus aculeatus).

PubMed

Kellner, M; Porseryd, T; Porsch-Hällström, I; Hansen, S H; Olsén, K H

2015-01-01

Selective Serotonin Re-uptake Inhibitors (SSRI) are mood-altering, psychotropic drugs commonly used in the treatment of depression and other psychological illnesses. Many of them are poorly degraded in sewage treatment plants and enter the environment unaltered. In laboratory studies, they have been demonstrated to affect a wide range of behaviours in aquatic organisms. In this study we investigated the effect of a three-week exposure to 0.15 and 1.5 μg/l of the SSRI citalopram dissolved in the ambient water on the feeding behaviour in three-spine stickleback (Gasterosteus aculeatus). Feeding, measured as the number of attacks performed on a piece of frozen bloodworms during a 10-min period, was reduced by 30-40% in fish exposed to both 0.15 and 1.5 μg/l citalopram. The effects of the environmentally relevant concentration 0.15 μg/l on feeding, an important fitness characteristic, suggests that the ecological significance of environmental SSRI exposure may be pronounced. Copyright © 2014 Elsevier B.V. All rights reserved.

Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs.

PubMed

Turner, Wendy C; Kausrud, Kyrre L; Beyer, Wolfgang; Easterday, W Ryan; Barandongo, Zoë R; Blaschke, Elisabeth; Cloete, Claudine C; Lazak, Judith; Van Ert, Matthew N; Ganz, Holly H; Turnbull, Peter C B; Stenseth, Nils Chr; Getz, Wayne M

2016-06-06

To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1-2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways.

Coral ontogeny affects early symbiont acquisition in laboratory-reared recruits

NASA Astrophysics Data System (ADS)

McIlroy, Shelby E.; Coffroth, Mary Alice

2017-09-01

In most coral species, the critical association with a subset of genetically diverse algal endosymbionts, Symbiodinium, is re-established anew each generation in early coral ontogeny. Yet little is known about the window during which these associations are established or the potential for altering symbiont associations through early exposure to non-native, and/or ecologically beneficial (e.g., stress tolerant), symbiont strains. This study examined the ontogenetic window of symbiont uptake in a restoration target species. Orbicella faveolata recruits, maintained aposymbiotic in laboratory tanks for 4 months, showed a significant decrease in symbiont acquisition upon exposure to natural seawater. Recruits initially inoculated with cultured Symbiodinium readily acquired additional strains from environmental symbiont populations upon exposure, but exogenous uptake also decreased in frequency after 4 months of laboratory rearing. Early exposure to Symbiodinium may benefit laboratory-reared recruits (e.g., enhance growth), but the potential for establishing long-term novel symbiotic associations may be limited.

Behavioral and biochemical adjustments of the zebrafish Danio rerio exposed to the β-blocker propranolol.

PubMed

Mitchell, Kimberly M; Moon, Thomas W

2016-09-01

Propranolol (PROP) is a β-blocker prescribed mainly to treat human cardiovascular diseases and as a result of its wide usage and persistence, it is reported in aquatic environments. This study examined whether PROP alters developmental patterns and catecholamine (CA)-regulated processes in the zebrafish (Danio rerio) and if exposure during early life alters the stress response and behaviors of adults. The calculated 48h larva LC50 was 21.6mg/L, well above reported environmental levels (0.01-0.59μg/L). Stressed and PROP-exposed adult zebrafish had reduced testosterone and estradiol levels and exhibited behaviors indicating less anxiety than control fish. Furthermore, adults previously PROP-exposed as embryos/larvae had decreased growth in terms of body length and mass. Finally, these adults showed increased cholesterol and a dose-dependent decrease in testosterone levels compared with unexposed zebrafish. Thus PROP-exposure of zebrafish embryos/larvae alters developmental patterns and CA-regulated processes that may affect normal behaviors and responses to stressors, and at least some of these changes persist in the adult zebrafish. Copyright © 2015 Elsevier Inc. All rights reserved.

PPTOX III: environmental stressors in the developmental origins of disease--evidence and mechanisms.

PubMed

Schug, Thaddeus T; Barouki, Robert; Gluckman, Peter D; Grandjean, Philippe; Hanson, Mark; Heindel, Jerold J

2013-02-01

Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards. Subtle effects during development can lead to functional deficits and increased disease risk later in life. The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies. Similar observations have been made on the long-term impact of nutritional unbalance during early development. In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work. This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees. Recommendations for the application and improvement of current and future research efforts are also presented.

Aneuploid sperm formation in rainbow trout exposed to the environmental estrogen 17α-ethynylestradiol

PubMed Central

Brown, Kim H.; Schultz, Irvin R.; Cloud, J. G.; Nagler, James J.

2008-01-01

Environmental contaminants that mimic native estrogens (i.e., environmental estrogens) are known to significantly impact a wide range of vertebrate species and have been implicated as a source for increasing human male reproductive deficiencies and diseases. Despite the widespread occurrence of environmental estrogens and recognized detrimental effects on male vertebrate reproduction, no specific mechanism has been determined indicating how reduced fertility and/or fecundity is achieved. Previous studies show that male rainbow trout, Oncorhynchus mykiss, exposed to the environmental estrogen 17α-ethynylestradiol (EE2) before gamete formation and fertilization produce progeny with significantly reduced embryonic survival. To determine whether this observed decrease results from sperm chromosome alterations during spermatogenesis, male rainbow trout were exposed to 10 ng of EE2/l for 50 days. After exposure, semen was collected and sperm aneuploidy levels analyzed with two chromosome markers by fluorescent in situ hybridization. In vitro fertilizations were also conducted by using control and exposed sperm crossed to eggs from an unexposed female for offspring analysis. Evaluations for nucleolar organizer region number and karyotype were performed on developing embryos to determine whether sperm aneuploidy translated into embryonic aneuploidy. Results conclusively show increased aneuploid sperm formation due to EE2 exposure. Additionally, embryonic cells from propagated progeny of individuals possessing elevated sperm aneuploidy display high levels of embryonic aneuploidy. This study concludes that EE2 exposure in sexually developing male rainbow trout increases levels of aneuploid sperm, providing a mechanism for decreased embryonic survival and ultimately diminished reproductive success in EE2 exposed males. PMID:19066213

Is Lead Exposure in Early Life An Environmental Risk Factor for Schizophrenia? Neurobiological Connections and Testable Hypotheses

PubMed Central

Guilarte, Tomás R.; Opler, Mark; Pletnikov, Mikhail

2013-01-01

Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb2+) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb2+ exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb2+ exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. PMID:22178136

Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.

2012-12-01

Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. 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 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increasemore » in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed. ► Males and females had changed percentages of numerous splenic cell populations. ► The antibody response of a streptococcal vaccine showed numerous changes.« less

Effect of Endocrine Disruptor Pesticides: A Review

PubMed Central

Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

2011-01-01

Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

Transcriptional responses of zebrafish to complex metal mixtures in laboratory studies overestimates the responses observed with environmental water.

PubMed

Pradhan, Ajay; Ivarsson, Per; Ragnvaldsson, Daniel; Berg, Håkan; Jass, Jana; Olsson, Per-Erik

2017-04-15

Metals released into the environment continue to be of concern for human health. However, risk assessment of metal exposure is often based on total metal levels and usually does not take bioavailability data, metal speciation or matrix effects into consideration. The continued development of biological endpoint analyses are therefore of high importance for improved eco-toxicological risk analyses. While there is an on-going debate concerning synergistic or additive effects of low-level mixed exposures there is little environmental data confirming the observations obtained from laboratory experiments. In the present study we utilized qRT-PCR analysis to identify key metal response genes to develop a method for biomonitoring and risk-assessment of metal pollution. The gene expression patterns were determined for juvenile zebrafish exposed to waters from sites down-stream of a closed mining operation. Genes representing different physiological processes including stress response, inflammation, apoptosis, drug metabolism, ion channels and receptors, and genotoxicity were analyzed. The gene expression patterns of zebrafish exposed to laboratory prepared metal mixes were compared to the patterns obtained with fish exposed to the environmental samples with the same metal composition and concentrations. Exposure to environmental samples resulted in fewer alterations in gene expression compared to laboratory mixes. A biotic ligand model (BLM) was used to approximate the bioavailability of the metals in the environmental setting. However, the BLM results were not in agreement with the experimental data, suggesting that the BLM may be overestimating the risk in the environment. The present study therefore supports the inclusion of site-specific biological analyses to complement the present chemical based assays used for environmental risk-assessment. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

PubMed

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Tertiary Epimutations – A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability

PubMed Central

McCarrey, John R.; Lehle, Jake D.; Raju, Seetha S.; Wang, Yufeng; Nilsson, Eric E.; Skinner, Michael K.

2016-01-01

Exposure to environmental factors can induce the epigenetic transgenerational inheritance of disease. Alterations to the epigenome termed “epimutations” include “primary epimutations” which are epigenetic alterations in the absence of genetic change and “secondary epimutations” which form following an initial genetic change. To determine if secondary epimutations contribute to transgenerational transmission of disease following in utero exposure to the endocrine disruptor vinclozolin, we exposed pregnant female rats carrying the lacI mutation-reporter transgene to vinclozolin and assessed the frequency of mutations in kidney tissue and sperm recovered from F1 and F3 generation progeny. Our results confirm that vinclozolin induces primary epimutations rather than secondary epimutations, but also suggest that some primary epimutations can predispose a subsequent accelerated accumulation of genetic mutations in F3 generation descendants that have the potential to contribute to transgenerational phenotypes. We therefore propose the existence of “tertiary epimutations” which are initial primary epimutations that promote genome instability leading to an accelerated accumulation of genetic mutations. PMID:27992467

Effects of maternal exposure to phthalates and bisphenol A during pregnancy on gestational age.

PubMed

Weinberger, Barry; Vetrano, Anna M; Archer, Faith E; Marcella, Stephen W; Buckley, Brian; Wartenberg, Daniel; Robson, Mark G; Klim, Jammie; Azhar, Sana; Cavin, Sarah; Wang, Lu; Rich, David Q

2014-03-01

Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation. Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery. Using linear regression models, we estimated the change in gestational age associated with each interquartile range (IQR) increase in phthalate and BPA metabolite concentration. IQR increases in urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BPA concentrations were associated with 4.2 and 1.1 d decreases in gestation, respectively. When stratified by gender, these alterations were found only in male infants. We conclude that MEHHP and BPA (free + glucuronide) are associated with reductions in gestation, with effects observed only in males. Our findings are consistent with the idea that these agents induce gender-specific alterations in signaling via PPAR-γ transcription factor, androgen precursors and/or inflammatory mediators during the initiation of labor.

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

PubMed Central

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

2017-01-01

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 alcohol and other drugs of abuse exert consistently note a disconnect 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 if 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 impact 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 changes in chromatin structure cannot unequivocally explain dysgenesis in isolation. PMID:28433419

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

PubMed

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 in chromatin structure cannot unequivocally explain dysgenesis in isolation. Copyright © 2017 Elsevier Inc. All rights reserved.

Staphylococcus aureus Redirects Central Metabolism to Increase Iron Availability

PubMed Central

Pishchany, Gleb; Whitwell, Corbin W; Torres, Victor J; Skaar, Eric P

2006-01-01

Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment) or genetic (Δfur) alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB), a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus. PMID:16933993

Histological and Transcriptomic Changes in Male Zebrafish Testes Due to Early Life Exposure to Low Level 2,3,7,8-Tetrachlorodibenzo-p-Dioxin.

PubMed

Baker, Bridget B; Yee, Jeremiah S; Meyer, Danielle N; Yang, Doris; Baker, Tracie R

2016-10-01

We have shown that zebrafish (Danio rerio) are an excellent model for evaluating the link between early life stage exposure to environmental chemicals and disease in adulthood and subsequent unexposed generations. Previously, we used this model to identify transgenerational effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on skeletal development, sex ratio, and reproductive capacity. Transgenerational inheritance of TCDD toxicity, notably decreased reproductive capacity, appears to be mediated through the male germ line. Thus, we examine testicular tissue for structural and gene expression changes using histology, microarray, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Histological analysis revealed decreased spermatozoa with concurrent increase in spermatogonia, and decreased germinal epithelium thickness in TCDD-exposed males compared with controls. We also identified altered expression of genes associated with testis development, steroidogenesis, spermatogenesis, hormone metabolism, and xenobiotic response. Altered genes are in pathways involving lipid metabolism, molecular transport, small molecule biochemistry, cell morphology, and metabolism of vitamins and minerals. These data will inform future investigations to elucidate the mechanism of adult-onset and transgenerational infertility due to TCDD exposure in zebrafish.

Tris (2-butoxyethyl) phosphate affects motor behavior and axonal growth in zebrafish (Danio rerio) larvae.

PubMed

Jiang, Fan; Liu, Jue; Zeng, Xinyue; Yu, Liqin; Liu, Chunsheng; Wang, Jianghua

2018-05-01

Tris (2-butoxyethyl) phosphate (TBOEP) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. Recently, the reproductive and developmental toxicology of TBOEP has been reported. However, fewer studies have assessed the neurotoxic effects in zebrafish (Danio rerio) larvae. In this study, zebrafish embryos were subjected to waterborne exposure of TBOEP at 0, 50, 500, 1500 and 2500 μg/L from 2 to 144-h post-fertilization (hpf). Behavioral measurements showed that TBOEP exposure reduced embryonic spontaneous movement and decreased swimming speed of larvae in response to dark stimulation. In accordance with these motor effects, TBOEP treatment reduced neuron-specific GFP expression in transgenic Tg (HuC-GFP) zebrafish larvae and inhibited the growth of secondary motoneurons, as well as decreased expression of marker genes related to central nervous system development in TBOEP treated group. Furthermore, increased concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduction of SOD activity were detected in TBOEP exposure group. The present results showed that the alteration in motor neuron and oxidative stress could together lead to the motor behavior alterations induced by TBOEP. Copyright © 2018 Elsevier B.V. All rights reserved.

Obesity and Metabolic Comorbidities: Environmental Diseases?

PubMed Central

Lubrano, Carla; Genovesi, Giuseppe; Specchia, Palma; Costantini, Daniela; Mariani, Stefania; Petrangeli, Elisa; Lenzi, Andrea; Gnessi, Lucio

2013-01-01

Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs) are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations. PMID:23577225

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

PubMed

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M; Wilks, Martin F; Spandidos, Demetrios A; Fenga, Concettina

2016-10-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review)

PubMed Central

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M.; Wilks, Martin F.; Spandidos, Demetrios A.; Fenga, Concettina

2016-01-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases. PMID:27600395

Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis)

PubMed Central

Tate, Kevin B.; Rhen, Turk; Eme, John; Kohl, Zachary F.; Crossley, Janna; Elsey, Ruth M.

2016-01-01

During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50–70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70–90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator. PMID:27101296

The effects of chronic acetaminophen exposure on the kidney, gill and liver in rainbow trout (Oncorhynchus mykiss).

PubMed

Choi, Eugene; Alsop, Derek; Wilson, Joanna Y

2018-05-01

In this study, we examined if rainbow trout chronically exposed to acetaminophen (10 and 30 μgL -1 ) showed histological changes that coincided with functional changes in the kidney, gill and liver. Histological changes in the kidney included movement and loss of nuclei, non-uniform nuclei size, non-uniform cytoplasmic staining, and loss of tubule integrity. Histological effects were more severe at the higher concentration and coincided with concentration dependent increases in urine flow rate and increased urinary concentrations of sodium, chloride, potassium, calcium, urea, ammonia, glucose, and protein. Yet, glomerular filtration rate was not altered with acetaminophen exposure. In the gill, filament end swelling, whole filament swelling, and swelling of the lamellae were observed in exposed fish. Lamellar spacing decreased in both exposure groups, but lamellar area decreased only with 30 μgL -1 exposure. At faster swimming speeds, oxygen consumption was limited in acetaminophen exposed fish, and critical swimming speed was also decreased in both exposure groups. The liver showed decreased perisinusoidal spaces at 10 and 30 μgL -1 acetaminophen, and decreased cytoplasmic vacuolation with 30 μgL -1 acetaminophen. A decrease in liver glycogen was also observed at 30 μgL -1 . There was no change in plasma concentrations of sodium, chloride, potassium, calcium, magnesium, and glucose with exposure, suggesting compensation for urinary loss. Indeed, an increase in Na + -K + -ATPase activity in the gills was found with 30 μgL -1 acetaminophen exposure. Chronic exposure of rainbow trout to the environmentally relevant pharmaceutical acetaminophen, alters both histology and function of organs responsible for ion and nutrient homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP reduced oocyte and blastocyst developmental competence up to F3. • DEHP altered expression levels for key genes in ovary and blastocysts up to F4. • DEHP's adverse effects were observed at doses relevant for human exposure.« less

Assessment of health status of oysters (Crassostreagigas) exposed to environmentally relevant concentrations of Ag and Cu in brackish waters

NASA Astrophysics Data System (ADS)

Rementeria, Ane; Mikolaczyk, Mathilde; Peña, Ainhize; Lanceleur, Laurent; Blanc, Gérard; Soto, Manu; Schäfer, Jörg; Zaldibar, Beñat

2017-12-01

Human activities have altered estuarine environments leading to increased presence of different pollutants including metals. Although the implementation of new environmental policies has caused a considerable decrease in trace metal concentrations in estuaries around the Bay of Biscay, some elements such as copper (Cu) and silver (Ag) are still present in relatively high concentrations. Oysters have been widely used in environmental biomonitoring programs as sentinel organisms. Oysters Crassostrea gigas from an uncontaminated estuary were exposed to sublethal, environmentally relevant concentrations of Cu (2000 ng Cu/L) and Ag (500 ng Ag/L) during 14 days in brackish water (S = 18). A battery of cell and tissue level (exposure) biomarkers at different levels of biological complexity was applied and integrated into the Integrative Biological Response (IBR) index including: metallothionein contents, intralysosomal metal accumulation, digestive gland atrophy and digestive gland tissue integrity. Condition Index (CI) was incorporated into the IBR index as a complementary parameter that reflects the general physiological condition of oysters (organism level). Results indicated an increase in intralysosomal metal accumulation after 7 and 14 days of exposure to Ag together with an increase in the digestive epithelium atrophy and lipofuscin content after 7 days of exposure to Ag. The responses detected with the aid of biomarkers integrated in the IBR index showed higher toxicity in oysters exposed to Ag, inducing the clear onset of detoxification processes which also occurred, to a lower extent, in Cu-exposed oysters.

Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)

PubMed Central

Laing, L. V.; Viana, J.; Dempster, E. L.; Trznadel, M.; Trunkfield, L. A.; Uren Webster, T. M.; van Aerle, R.; Paull, G. C.; Wilson, R. J.; Mill, J.; Santos, E. M.

2016-01-01

ABSTRACT Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment. PMID:27120497

Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

PubMed Central

Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M. A.; Romero, Juan I.; Holubiec, Mariana I.; Rodríguez de Fonseca, Fernando; Capani, Francisco

2015-01-01

Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia. PMID:25601829

Adult acclimation to combined temperature and pH stressors significantly enhances reproductive outcomes compared to short-term exposures.

PubMed

Suckling, Coleen C; Clark, Melody S; Richard, Joelle; Morley, Simon A; Thorne, Michael A S; Harper, Elizabeth M; Peck, Lloyd S

2015-05-01

This study examined the effects of long-term culture under altered conditions on the Antarctic sea urchin, Sterechinus neumayeri. Sterechinus neumayeri was cultured under the combined environmental stressors of lowered pH (-0.3 and -0.5 pH units) and increased temperature (+2 °C) for 2 years. This time-scale covered two full reproductive cycles in this species and analyses included studies on both adult metabolism and larval development. Adults took at least 6-8 months to acclimate to the altered conditions, but beyond this, there was no detectable effect of temperature or pH. Animals were spawned after 6 and 17 months exposure to altered conditions, with markedly different outcomes. At 6 months, the percentage hatching and larval survival rates were greatest in the animals kept at 0 °C under current pH conditions, whilst those under lowered pH and +2 °C performed significantly less well. After 17 months, performance was not significantly different across treatments, including controls. However, under the altered conditions urchins produced larger eggs compared with control animals. These data show that under long-term culture adult S. neumayeri appear to acclimate their metabolic and reproductive physiology to the combined stressors of altered pH and increased temperature, with relatively little measureable effect. They also emphasize the importance of long-term studies in evaluating effects of altered pH, particularly in slow developing marine species with long gonad maturation times, as the effects of altered conditions cannot be accurately evaluated unless gonads have fully matured under the new conditions. © 2014 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Embryonic exposure to environmentally relevant concentrations of a brominated flame retardant reduces the size of song-control nuclei in a songbird.

PubMed

Eng, Margaret L; Winter, Viktoria; Elliott, John E; MacDougall-Shackleton, Scott A; Williams, Tony D

2018-05-22

Environmental contaminants have the potential to act as developmental stressors and impair development of song and the brain of songbirds, but they have been largely unstudied in this context. 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is a brominated flame retardant congener that has demonstrated endocrine disrupting effects, and has pervaded the global environment. We assessed the effects of in ovo exposure to environmentally relevant levels of BDE-99 on the neuroanatomy of the song-control system in a model songbird species, the zebra finch (Taeniopygia guttata). Embryos were exposed via egg injection to a vehicle control (DMSO), 10, 100 or 1000 ng BDE-99/g egg on the day the egg was laid. Chicks were raised to sexual maturity to investigate long-term effects of BDE-99 on the adult male brain. Three key song-control nuclei (Area X, HVC, RA) all showed a dose-dependent trend toward decreasing volume as BDE-99 concentration increased, and birds exposed to 1000 ng/g in ovo BDE-99 had significantly smaller song-control nuclei volume compared to control birds. High environmental concentrations of BDE-99 in avian tissues can be within that range and thus could affect development of the song-control system in birds, and potentially other processes. We previously found that BDE-99 exposure during the nestling period had no effect of on the song-control system, although it did have significant effects on some behavioural endpoints. Taken together, these results suggest that exposure to PBDEs during critical developmental windows can significantly alter neurological development. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Global DNA methylation loss associated with mercury contamination and aging in the American alligator (Alligator mississippiensis).

PubMed

Nilsen, Frances M; Parrott, Benjamin B; Bowden, John A; Kassim, Brittany L; Somerville, Stephen E; Bryan, Teresa A; Bryan, Colleen E; Lange, Ted R; Delaney, J Patrick; Brunell, Arnold M; Long, Stephen E; Guillette, Louis J

2016-03-01

Mercury is a widespread environmental contaminant with exposures eliciting a well-documented catalog of adverse effects. Yet, knowledge regarding the underlying mechanisms by which mercury exposures are translated into biological effects remains incomplete. DNA methylation is an epigenetic modification that is sensitive to environmental cues, and alterations in DNA methylation at the global level are associated with a variety of diseases. Using a liquid chromatography tandem mass spectrometry-based (LC-MS/MS) approach, global DNA methylation levels were measured in red blood cells of 144 wild American alligators (Alligator mississippiensis) from 6 sites with variable levels of mercury contamination across Florida's north-south axis. Variation in mercury concentrations measured in whole blood was highly associated with location, allowing the comparison of global DNA methylation levels across different "treatments" of mercury. Global DNA methylation in alligators across all locations was weakly associated with increased mercury exposure. However, a much more robust relationship was observed in those animals sampled from locations more highly contaminated with mercury. Also, similar to other vertebrates, global DNA methylation appears to decline with age in alligators. The relationship between age-associated loss of global DNA methylation and varying mercury exposures was examined to reveal a potential interaction. These findings demonstrate that global DNA methylation levels are associated with mercury exposure, and give insights into interactions between contaminants, aging, and epigenetics. Published by Elsevier B.V.

Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model

PubMed Central

Marjonen, Heidi; Sierra, Alejandra; Nyman, Anna; Rogojin, Vladimir; Gröhn, Olli; Linden, Anni-Maija; Hautaniemi, Sampsa; Kaminen-Ahola, Nina

2015-01-01

The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P) 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60): we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in different tissue types later in life. PMID:25970770

Food safety involving ingestion of foods and beverages prepared with phthalate-plasticizer-containing clouding agents.

PubMed

Yen, Tzung-Hai; Lin-Tan, Dan-Tzu; Lin, Ja-Liang

2011-11-01

In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of phthalate-related scientific publications from Taiwan has increased greatly over the past 5 years, which may reflect the health effects from the illegal addition of phthalate plasticizer to clouding agent in foodstuff over the past two decades. Copyright © 2011. Published by Elsevier B.V.

Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

PubMed

Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

2010-04-01

Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas).

USGS Publications Warehouse

Furlong, Edward T.; Barber, Larry B.; Meghan R. McGee,; Megan A. Buerkley,; Matthew L. Julius,; Vajda, Alan M.; Heiko L. Schoenfuss,; Schultz, Melissa M.; Norris, David O.

2009-01-01

The effects of embryonic and larval exposure to environmentally relevant (ng/L) concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine, and bupropion (singularly and in mixture) on C-start escape behavior were evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization until hatching) were exposed for 5 d and, after hatching, were allowed to grow in control well water until 12 d old. Similarly, posthatch fathead minnows were exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by- frame analysis of latency periods, escape velocities, and total escape response (combination of latency period and escape velocity). When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d posthatch did not exhibit altered escape responses when exposed to fluoxetine but were affected by venlafaxine and bupropion exposure. Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window. The direct impact of reduced C-start performance on survival and, ultimately, reproductive fitness provides an avenue to assess the ecological relevance of exposure in an assay of relatively short duration.

Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas)

USGS Publications Warehouse

Painter, M.M.; Buerkley, M.A.; Julius, M.L.; Vajda, A.M.; Norris, D.O.; Barber, L.B.; Furlong, E.T.; Schultz, M.M.; Schoenfuss, H.L.

2009-01-01

The effects of embryonic and larval exposure to environmentally relevant (ng/L) concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine, and bupropion (singularly and in mixture) on C-start escape behavior were evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization until hatching) were exposed for 5 d and, after hatching, were allowed to grow in control well water until 12 d old. Similarly, posthatch fathead minnows were exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by-frame analysis of latency periods, escape velocities, and total escape response (combination of latency period and escape velocity). When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d posthatch did not exhibit altered escape responses when exposed to fluoxetine but were affected by venlafaxine and bupropion exposure. Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window. The direct impact of reduced C-start performance on survival and, ultimately, reproductive fitness provides an avenue to assess the ecological relevance of exposure in an assay of relatively short duration. ?? 2009 SETAC.

Parental tobacco smoke exposure: Epigenetics and the ...

EPA Pesticide Factsheets

Epigenetic programming is an important mechanism underlying the Developmental Origins of Health and Disease (DOHaD). Much of the research in this area has focused on maternal nutrition. Parental smoking has emerged as a prime example of how exposure to environmental toxicants during the preconceptional and in utero periods can have long-term effects on offspring health, and the role of the epigenome in these effects. Maternal smoking and exposure to second-hand smoke during pregnancy result in lower birth weight of offspring, and there is now clear evidence that these offspring are at elevated risk for overweight/obesity, type-2 diabetes, respiratory effects during adolescence and adulthood, and may be programmed for increased risk of nicotine addiction. Epigenetic analyses of placenta, cord blood and offspring buccal cells have consistently revealed altered DNA methylation of genes involved in developmental processes and xenobiotic metabolism, and these epigenetic changes are persistent. Animal studies with cigarette smoke and nicotine support these findings. Paternal preconceptional smoking has been positively related to childhood cancers, potentially linked to changes in the sperm epigenome. Germ cell specification and preimplantation development are periods of widespread erasure and reprogramming of DNA methylation, and as such are likely to be sensitive periods for environmental effects on the epigenome. Exposure to tobacco smoke during gametogenesis and in

Developmental exposure to trichloroethylene promotes CD4{sup +} T cell differentiation and hyperactivity in association with oxidative stress and neurobehavioral deficits in MRL+/+ mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blossom, Sarah J.; Doss, Jason C.; Hennings, Leah J.

2008-09-15

The non adult immune system is particularly sensitive to perinatal and early life exposures to environmental toxicants. The common environmental toxicant, trichloroethylene (TCE), was shown to increase CD4+ T cell production of the proinflammatory cytokine IFN-{gamma} following a period of prenatal and lifetime exposure in autoimmune-prone MRL+/+ mice. In the current study, MRL+/+ mice were used to further examine the impact of TCE on the immune system in the thymus and periphery. Since there is considerable cross-talk between the immune system and the brain during development, the potential relationship between TCE and neurobehavioral endpoints were also examined. MRL+/+ mice weremore » exposed to 0.1 mg/ml TCE ({approx} 31 mg/kg/day) via maternal drinking water or direct exposure via the drinking water from gestation day 1 until postnatal day (PD) 42. TCE exposure did not impact gross motor skills but instead significantly altered social behaviors and promoted aggression associated with indicators of oxidative stress in brain tissues in male mice. The immunoregulatory effects of TCE involved a redox-associated promotion of T cell differentiation in the thymus that preceded the production of proinflammatory cytokines, IL-2, TNF-{alpha}, and IFN-{gamma} by mature CD4+ T cells. The results demonstrated that developmental and early life TCE exposure modulated immune function and may have important implications for neurodevelopmental disorders.« less

Altering Genomic Integrity: Heavy Metal Exposure Promotes Transposable Element-Mediated Damage.

PubMed

Morales, Maria E; Servant, Geraldine; Ade, Catherine; Roy-Engel, Astrid M

2015-07-01

Maintenance of genomic integrity is critical for cellular homeostasis and survival. The active transposable elements (TEs) composed primarily of three mobile element lineages LINE-1, Alu, and SVA comprise approximately 30% of the mass of the human genome. For the past 2 decades, studies have shown that TEs significantly contribute to genetic instability and that TE-caused damages are associated with genetic diseases and cancer. Different environmental exposures, including several heavy metals, influence how TEs interact with its host genome increasing their negative impact. This mini-review provides some basic knowledge on TEs, their contribution to disease, and an overview of the current knowledge on how heavy metals influence TE-mediated damage.

Developmental origins of epigenetic transgenerational inheritance

PubMed Central

Hanson, Mark A.; Skinner, Michael K.

2016-01-01

Abstract Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis

DOE PAGES

Almeida-Porada, Graca; Rodman, Christopher; Kuhlman, Bradford; ...

2018-04-26

The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human HSC to simulated SEP and GCRmore » radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In the present study, we performed the first in depth examination to define changes that occur in mesenchymal stem cells (MSC) present in the human BM niche following exposure to accelerated protons and iron ions, and assess the impact these changes have upon human hematopoiesis. Here, our data thus provides compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called “biological bystander effects” by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.« less

Nocturnal light exposure impairs affective responses in a wavelength-dependent manner.

PubMed

Bedrosian, Tracy A; Vaughn, Celynn A; Galan, Anabel; Daye, Ghassan; Weil, Zachary M; Nelson, Randy J

2013-08-07

Life on earth is entrained to a 24 h solar cycle that synchronizes circadian rhythms in physiology and behavior; light is the most potent entraining cue. In mammals, light is detected by (1) rods and cones, which mediate visual function, and (2) intrinsically photosensitive retinal ganglion cells (ipRGCs), which primarily project to the suprachiasmatic nucleus (SCN) in the hypothalamus to regulate circadian rhythms. Recent evidence, however, demonstrates that ipRGCs also project to limbic brain regions, suggesting that, through this pathway, light may have a role in cognition and mood. Therefore, it follows that unnatural exposure to light may have negative consequences for mood or behavior. Modern environmental lighting conditions have led to excessive exposure to light at night (LAN), and particularly to blue wavelength lights. We hypothesized that nocturnal light exposure (i.e., dim LAN) would induce depressive responses and alter neuronal structure in hamsters (Phodopus sungorus). If this effect is mediated by ipRGCs, which have reduced sensitivity to red wavelength light, then we predicted that red LAN would have limited effects on brain and behavior compared with shorter wavelengths. Additionally, red LAN would not induce c-Fos activation in the SCN. Our results demonstrate that exposure to LAN influences behavior and neuronal plasticity and that this effect is likely mediated by ipRGCs. Modern sources of LAN that contain blue wavelengths may be particularly disruptive to the circadian system, potentially contributing to altered mood regulation.

Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Almeida-Porada, Graca; Rodman, Christopher; Kuhlman, Bradford

The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human HSC to simulated SEP and GCRmore » radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In the present study, we performed the first in depth examination to define changes that occur in mesenchymal stem cells (MSC) present in the human BM niche following exposure to accelerated protons and iron ions, and assess the impact these changes have upon human hematopoiesis. Here, our data thus provides compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called “biological bystander effects” by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.« less

Epigenetic Perspective on the Developmental Effects of Bisphenol A

PubMed Central

Kundakovic, Marija; Champagne, Frances A.

2013-01-01

Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to public health. Animal studies suggest that in utero and early postnatal exposure to this compound may produce a broad range of adverse effects, including impaired brain development, sexual differentiation, behavior, and immune function, which could extend to future generations. Molecular mechanisms that underlie the long-lasting effects of BPA continue to be elucidated, and likely involve disruption of epigenetic programming of gene expression during development. Several studies have provided evidence that maternal exposure to BPA results in postnatal changes in DNA methylation status and altered expression of specific genes in offspring. However, further studies are needed to extend these initial findings to other genes in different tissues, and to examine the correlations between BPA-induced epigenetic alterations, changes in gene expression, and various phenotypic outcomes. It will be also important to explore whether the epigenetic effects of BPA are related to its estrogenic activity, and to determine which downstream effector proteins could mediate changes in DNA methylation. In this review, we will highlight research indicating a consequence of prenatal BPA exposure for brain, behavior, and immune outcomes and discuss evidence for the role of epigenetic pathways in shaping these developmental effects. Based on this evidence, we will suggest future directions in the study of BPA-induced epigenetic effects and discuss the transgenerational implications of exposure to endocrine disrupting chemicals. PMID:21333735

Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis.

PubMed

Almeida-Porada, Graça; Rodman, Christopher; Kuhlman, Bradford; Brudvik, Egil; Moon, John; George, Sunil; Guida, Peter; Sajuthi, Satria P; Langefeld, Carl D; Walker, Stephen J; Wilson, Paul F; Porada, Christopher D

2018-04-26

The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human hematopoietic stem cells (HSC) to simulated solar energetic particle (SEP) and galactic cosmic ray (GCR) radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In this study, we performed the first in-depth examination to define changes that occur in mesenchymal stem cells present in the human BM niche following exposure to accelerated protons and iron ions and assess the impact these changes have upon human hematopoiesis. Our data provide compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called "biological bystander effects" by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.

Rapid transcriptome responses of maize (Zea mays) to UV-B in irradiated and shielded tissues

PubMed Central

Casati, Paula; Walbot, Virginia

2004-01-01

Background Depletion of stratospheric ozone has raised terrestrial levels of ultraviolet-B radiation (UV-B), an environmental change linked to an increased risk of skin cancer and with potentially deleterious consequences for plants. To better understand the processes of UV-B acclimation that result in altered plant morphology and physiology, we investigated gene expression in different organs of maize at several UV-B fluence rates and exposure times. Results Microarray hybridization was used to assess UV-B responses in directly exposed maize organs and organs shielded by a plastic that absorbs UV-B. After 8 hours of high UV-B, the abundance of 347 transcripts was altered: 285 were increased significantly in at least one organ and 80 were downregulated. More transcript changes occurred in directly exposed than in shielded organs, and the levels of more transcripts were changed in adult compared to seedling tissues. The time course of transcript abundance changes indicated that the response kinetics to UV-B is very rapid, as some transcript levels were altered within 1 hour of exposure. Conclusions Most of the UV-B regulated genes are organ-specific. Because shielded tissues, including roots, immature ears, and leaves, displayed altered transcriptome profiles after exposure of the plant to UV-B, some signal(s) must be transmitted from irradiated to shielded tissues. These results indicate that there are integrated responses to UV-B radiation above normal levels. As the same total UV-B irradiation dose applied at three intensities elicited different transcript profiles, the transcriptome changes exhibit threshold effects rather than a reciprocal dose-effect response. Transcriptome profiling highlights possible signaling pathways and molecules for future research. PMID:15003119

DNA methylation in complex disease: applications in nursing research, practice, and policy.

PubMed

Wright, Michelle L; Ralph, Jody L; Ohm, Joyce E; Anderson, Cindy M

2013-01-01

DNA methylation is an epigenomic modification that is essential to normal human development and biological processes. DNA methylation patterns are heritable and dynamic throughout the life span. Environmental exposures can alter DNA methylation patterns, contributing to the development of complex disease. Identification and modulation of environmental factors influencing disease susceptibility through alterations in DNA methylation are amenable to nursing intervention and form the basis for individualized patient care. Here we describe the evidence supporting the translation of DNA methylation analyses as a tool for screening, diagnosis, and treatment of complex disease in nursing research and practice. The ethical, legal, social, and economic considerations of advances in genomics are considered as a model for epigenomic policy. We conclude that contemporary and informed nurse scientists and clinicians are uniquely poised to apply innovations in epigenomic research to clinical populations and develop appropriate policies that guide equitable and ethical use of new strategies to improve patient care. Copyright © 2013 Elsevier Inc. All rights reserved.

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

Effect of cadmium exposure on hepatopancreas and gills of the estuary mud crab (Scylla paramamosain): Histopathological changes and expression characterization of stress response genes.

PubMed

Zhu, Qi-Hui; Zhou, Zhong-Kai; Tu, Dan-Dan; Zhou, Yi-Lian; Wang, Cong; Liu, Ze-Peng; Gu, Wen-Bin; Chen, Yu-Yin; Shu, Miao-An

2018-02-01

Cadmium (Cd) is a heavy metal that accumulates easily in organisms and causes several detrimental effects, including tissue damage. Cd contamination from anthropogenic terrestrial sources flows into rivers, and through estuaries to the ocean. To evaluate the toxic effects of Cd on estuary crustaceans, we exposed the mud crab Scylla paramamosain to various Cd concentrations (0, 10.0, 20.0, and 40.0mg/L) for 24h. We also exposed mud crabs to a fixed Cd concentration (20.0mg/L) for various periods of time (0, 6, 12, 24, 48, and 72h). We observed that after exposure to Cd, the surfaces of the gill lamellae were wrinkled, and the morphologies of the nuclei and mitochondria in the hepatopancreas were altered. We analyzed the expression profiles of 36 stress-related genes after Cd exposure, including those encoding metallothioneins, heat shock proteins, apoptosis-related proteins, and antioxidant proteins, with quantitative reverse transcription PCR. We found that exposure to Cd altered gene expression, and that some genes might be suitable bioindicators of Cd stress. Gene expression profiles were organ-, duration-, and concentration-dependent, suggesting that stress-response genes might be involved in an innate defense system for handling heavy metal exposure. To the best of our knowledge, this study is the first one of histopathology and stress-response gene expression pattern of Scylla paramamosain after Cd exposure. Our work could increase our understanding of the effect of environmental toxins on estuary crustaceans. Copyright © 2017 Elsevier B.V. All rights reserved.

Formaldehyde gas exposure increases inflammation in an in vitro model of dry eye.

PubMed

Vitoux, Michael-Adrien; Kessal, Karima; Baudouin, Christophe; Melik Parsadaniantz, Stéphane; Achard, Sophie; Brignole-Baudouin, Françoise

2018-05-31

Dry eye (DE) is a multifactorial ocular surface disease whose incidence continues to rise. Various environmental stresses such as low air humidity and pollution are known to be involved in epithelial alterations inducing ocular discomfort. However, no experimental study assessing the combined effects of dry air and polluted atmospheres has been conducted so far. Formaldehyde (FA) is a ubiquitous pollutant present in the living spaces where humans spend most of their time. Using an in vitro DE model, we evaluated the cytotoxic and inflammatory responses of a conjunctival cell line exposed at the air-liquid interface (ALI) conditions to various controlled atmospheres combining low humidity (LH), airflow (AF) and formaldehyde gas (FG). Conjunctiva-derived cells grown onto transwell inserts were directly exposed to LH conditions without AF, with AF or with FG flow at 100 or 1200 µg/m3 for 15-30 min. Cell viability assays revealed an increase in cell death after a 15-min exposure to FG at 100 or 1200 µg/m3, whatever the recovery period. After a 1-h recovery period, an increase in IL-6 and CXCL8/IL-8 gene expression was observed with the 15-min exposure at 100 µg/m3 FG and with 30 min of exposure at 1200 µg/m3 FG. After 24 h of recovery, we also noted increased secretion of the pro-inflammatory cytokine MIF with 100 µg/m3 FG exposure and CXCL8/IL-8 at 1200 µg/m3, for both exposure periods. Together, these findings suggest that the exposure to FG at environmental levels aggravates cell death and inflammation observed in dry air conditions. This in vitro model of DE seems to be a relevant tool to study and explain the inflammatory responses observed in dry eye patients when exposed to combined environmental disturbances such as low humidity, airflow, and the presence of airborne pollutants.

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.

2014-11-15

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylationmore » of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation of histone H4 (Lys 16). • Continual extended exposure to arsenic reorganises the pattern of SIRT1 and miR-34a promoter methylation.« less

Mechanistic insight into neurotoxicity induced by developmental insults

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamm, Christoffer; Ceccatelli, Sandra

Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells tomore » investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.« less

Developmental vitamin D deficiency and schizophrenia: the role of animal models

PubMed Central

Schoenrock, S. A.; Tarantino, L. M.

2016-01-01

Schizophrenia is a debilitating neuropsychiatric disorder that affects 1% of the US population. Based on twin and genome-wide association studies, it is clear that both genetics and environmental factors increase the risk for developing schizophrenia. Moreover, there is evidence that conditions in utero, either alone or in concert with genetic factors, may alter neurodevelopment and lead to an increased risk for schizophrenia. There has been progress in identifying genetic loci and environmental exposures that increase risk, but there are still considerable gaps in our knowledge. Furthermore, very little is known about the specific neurodevelopmental mechanisms upon which genetics and the environment act to increase disposition to developing schizophrenia in adulthood. Vitamin D deficiency during the perinatal period has been hypothesized to increase risk for schizophrenia in humans. The developmental vitamin D (DVD) deficiency hypothesis of schizophrenia arises from the observation that disease risk is increased in individuals who are born in winter or spring, live further from the equator or live in urban vs. rural settings. These environments result in less exposure to sunlight, thereby reducing the initial steps in the production of vitamin D. Rodent models have been developed to characterize the behavioral and developmental effects of DVD deficiency. This review focuses on these animal models and discusses the current knowledge of the role of DVD deficiency in altering behavior and neurobiology relevant to schizophrenia. PMID:26560996

Epigenetics and cardiovascular risk in childhood.

PubMed

Martino, Francesco; Magenta, Alessandra; Pannarale, Giuseppe; Martino, Eliana; Zanoni, Cristina; Perla, Francesco M; Puddu, Paolo E; Barillà, Francesco

2016-08-01

Cardiovascular disease (CVD) can arise at the early stages of development and growth. Genetic and environmental factors may interact resulting in epigenetic modifications with abnormal phenotypic expression of genetic information without any change in the nucleotide sequence of DNA. Maternal dietary imbalance, inadequate to meet the nutritional needs of the fetus can lead to intrauterine growth retardation, decreased gestational age, low birth weight, excessive post-natal growth and metabolic alterations, with subsequent appearance of CVD risk factors. Fetal exposure to high cholesterol, diabetes and maternal obesity is associated with increased risk and progression of atherosclerosis. Maternal smoking during pregnancy and exposure to various environmental pollutants induce epigenetic alterations of gene expression relevant to the onset or progression of CVD. In children with hypercholesterolemia and/or obesity, oxidative stress activates platelets and monocytes, which release proinflammatory and proatherogenic substances, inducing endothelial dysfunction, decreased Doppler flow-mediated dilation and increased carotid intima-media thickness. Primary prevention of atherosclerosis should be implemented early. It is necessary to identify, through screening, high-risk apparently healthy children and take care of them enforcing healthy lifestyle (mainly consisting of Mediterranean diet and physical activity), prescribing nutraceuticals and eventual medications, if required by a high-risk profile. The key issue is the restoration of endothelial function in the reversible stage of atherosclerosis. Epigenetics may provide new markers for an early identification of children at risk and thereby develop innovative therapies and specific nutritional interventions in critical times.

Effects of Tributyltin and Other Retinoid Receptor Agonists in Reproductive-Related Endpoints in the Zebrafish (Danio rerio).

PubMed

Lima, Daniela; Castro, L Filipe C; Coelho, Inês; Lacerda, Ricardo; Gesto, Manuel; Soares, Joana; André, Ana; Capela, Ricardo; Torres, Tiago; Carvalho, António Paulo; Santos, Miguel M

2015-01-01

Both field and experimental data examined the influence of exposure to environmental contaminant tributyltin (TBT) on marine organisms. Although most attention focused on the imposex phenomenon in gastropods, adverse effects were also observed in other taxonomic groups. It has been shown that imposex induction involves modulation of retinoid signaling in gastropods. Whether TBT influences similar pathways in fish is yet to be addressed. In this study, larvae of the model teleost Danio rerio were exposed to natural retinoids, all-trans-retinoic acid, 9-cis-retinoic acid, and all-trans-retinol, as well as to the RXR synthetic pan-agonist methoprene acid (MA) and to TBT. Larvae were exposed to TBT from 5 days post fertilization (dpf) to adulthood, and reproductive capacity was assessed and correlated with mode of action. TBT significantly decreased fecundity at environmentally relevant levels at 1 μg TBT Sn/g in diet. Interestingly, in contrast to previous reports, TBT altered zebrafish sex ratio toward females, whereas MA exposure biased sex toward males. Since fecundity was significantly altered in the TBT-exposed group with up to 62% decrease, the potentially affected pathways were investigated. Significant downregulation was observed in brain mRNA levels of aromatase b (CYP19a1b) in females and peroxisome proliferator activated receptor gamma (PPARg) in both males and females, suggesting an involvement of these pathways in reproductive impairment associated with TBT.

Cocaine Self-Administration in Male and Female Rats Perinatally Exposed to PCBs: Evaluating Drug Use in an Animal Model of Environmental Contaminant Exposure

PubMed Central

Miller, Mellessa M.; Meyer, Abby E.; Sprowles, Jenna L. N.; Sable, Helen J. K.

2017-01-01

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (i.v. SA) for the psychostimulant cocaine. Long Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared to non-exposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25 – 500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures. PMID:28287790

Transgenerational endocrine disruption and neurotoxicity in zebrafish larvae after parental exposure to binary mixtures of decabromodiphenyl ether (BDE-209) and lead.

PubMed

Chen, Lianguo; Wang, Xianfeng; Zhang, Xiaohua; Lam, Paul K S; Guo, Yongyong; Lam, James C W; Zhou, Bingsheng

2017-11-01

Polybrominated diphenyl ethers (PBDEs) and heavy metals are two key groups of electric and electronic equipment contaminants. Despite their co-occurrence in aquatic environments, their combined effects remain largely unknown, particularly under a chronic exposure regime. In the present study, adult zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of BDE-209 and lead (Pb), or their binary mixtures, for 3 months. After chronic parental exposure, increased transfer of BDE-209 and Pb to the offspring eggs was activated in the coexposure groups, with BDE-197 being the predominant PBDE congener, indicating the dynamic metabolism of BDE-209 in parental zebrafish. In the presence of Pb, culturing the eggs in clean water until 5 days post-fertilization (dpf) further accelerated the debromination of BDE-209 towards BDE-197 in the offspring, caused by the preferential removal of bromine atoms at meta positions. BDE-209 and Pb combinations induced reproductive and thyroid endocrine disruption in adults, which resulted in an imbalanced deposition of hormones in the eggs. However, compared with single chemical exposure, the larval offspring at 5 dpf from the coexposure groups had reversed the adverse influences from maternal origin. In addition, the interaction between BDE-209 and Pb led to transgenerational developmental neurotoxicity in the larval offspring, where inhibited neuronal growth and neurotransmitter signaling, disorganized muscular assembly, and impaired visual function contributed to the observed neurobehavioral deficits. Overall, depending on specific biological events, the complex interaction between BDE-209 and Pb under chronic exposure resulted in significant alterations in their environmental fate and toxicological actions, thus complicating the accurate evaluation of ecological risks and constituting an unquantified threat to environmental safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations.

PubMed

Tung, Emily W Y; Yan, Han; Lefèvre, Pavine L C; Berger, Robert G; Rawn, Dorothea F K; Gaertner, Dean W; Kawata, Alice; Rigden, Marc; Robaire, Bernard; Hales, Barbara F; Wade, Michael G

2016-06-01

Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague-Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30-45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity. © 2016 Wiley Periodicals, Inc.

Challenges and opportunities for managing aquatic mercury pollution in altered landscapes.

PubMed

Hsu-Kim, Heileen; Eckley, Chris S; Achá, Dario; Feng, Xinbin; Gilmour, Cynthia C; Jonsson, Sofi; Mitchell, Carl P J

2018-03-01

The environmental cycling of mercury (Hg) can be affected by natural and anthropogenic perturbations. Of particular concern is how these disruptions increase mobilization of Hg from sites and alter the formation of monomethylmercury (MeHg), a bioaccumulative form of Hg for humans and wildlife. The scientific community has made significant advances in recent years in understanding the processes contributing to the risk of MeHg in the environment. The objective of this paper is to synthesize the scientific understanding of how Hg cycling in the aquatic environment is influenced by landscape perturbations at the local scale, perturbations that include watershed loadings, deforestation, reservoir and wetland creation, rice production, urbanization, mining and industrial point source pollution, and remediation. We focus on the major challenges associated with each type of alteration, as well as management opportunities that could lessen both MeHg levels in biota and exposure to humans. For example, our understanding of approximate response times to changes in Hg inputs from various sources or landscape alterations could lead to policies that prioritize the avoidance of certain activities in the most vulnerable systems and sequestration of Hg in deep soil and sediment pools. The remediation of Hg pollution from historical mining and other industries is shifting towards in situ technologies that could be less disruptive and less costly than conventional approaches. Contemporary artisanal gold mining has well-documented impacts with respect to Hg; however, significant social and political challenges remain in implementing effective policies to minimize Hg use. Much remains to be learned as we strive towards the meaningful application of our understanding for stakeholders, including communities living near Hg-polluted sites, environmental policy makers, and scientists and engineers tasked with developing watershed management solutions. Site-specific assessments of MeHg exposure risk will require new methods to predict the impacts of anthropogenic perturbations and an understanding of the complexity of Hg cycling at the local scale.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.

Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in responsemore » to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening strategies should therefore consider how exposure to these materials alters susceptibility to other environmental exposures.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badham, Helen J.; Winn, Louise M., E-mail: winnl@queensu.c; School of Environmental Studies, Queen's University, Kingston, Ontario, K7L 3N6

Benzene is a ubiquitous occupational and environmental toxicant. Exposures to benzene both prenatally and during adulthood are associated with the development of disorders such as aplastic anemia and leukemia. Mechanisms of benzene toxicity are unknown; however, generation of reactive oxygen species (ROS) by benzene metabolites may play a role. Little is known regarding the effects of benzene metabolites on erythropoiesis. Therefore, to determine the effects of in utero exposure to benzene on the growth and differentiation of fetal erythroid progenitor cells (CFU-E), pregnant CD-1 mice were exposed to benzene and CFU-E numbers were assessed in fetal liver (hematopoietic) tissue. Inmore » addition, to determine the effect of benzene metabolite-induced ROS generation on erythropoiesis, HD3 chicken erythroblast cells were exposed to benzene, phenol, or hydroquinone followed by stimulation of erythrocyte differentiation. Our results show that in utero exposure to benzene caused significant alterations in female offspring CFU-E numbers. In addition, exposure to hydroquinone, but not benzene or phenol, significantly reduced the percentage of differentiated HD3 cells, which was associated with an increase in ROS. Pretreatment of HD3 cells with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) prevented hydroquinone-induced inhibition of erythropoiesis, supporting the hypothesis that ROS generation is involved in the development of benzene erythrotoxicity. In conclusion, this study provided evidence that ROS generated as a result of benzene metabolism may significantly alter erythroid differentiation, potentially leading to the development of Blood Disorders.« less

Genome-wide gene expression changes associated with exposure of rat liver, heart, and kidney cells to endosulfan.

PubMed

Liu, Ruifeng; Printz, Richard L; Jenkins, Erin C; O'Brien, Tracy P; Te, Jerez A; Shiota, Masakazu; Wallqvist, Anders

2018-04-01

Endosulfan was once the most commonly used pesticide in agriculture and horticulture. It is an environmentally persistent organochlorine compound with the potential to bioaccumulate as it progresses through the food chain. Its acute and chronic toxicity to mammals, including humans, is well known, but the molecular mechanisms of its toxicity are not fully understood. To gain insight to these mechanisms, we examined genome-wide gene expression changes of rat liver, heart, and kidney cells induced by endosulfan exposure. We found that among the cell types examined, kidney and liver cells were the most sensitive and most resilient, respectively, to endosulfan insult. We acquired RNA sequencing information from cells exposed to endosulfan to identify differentially expressed genes, which we further examined to determine the cellular pathways that were affected. In kidney cells, exposure to endosulfan was uniquely associated with altered expression levels of genes constituting the hypoxia-inducible factor-1 (HIF-1) signaling pathway. In heart and liver cells, exposure to endosulfan altered the expression levels of genes for many members of the extracellular matrix (ECM)-receptor interaction pathway. Because both HIF-1 signaling and ECM-receptor interaction pathways directly or indirectly control cell growth, differentiation, proliferation, and apoptosis, our findings suggest that dysregulation of these pathways is responsible for endosulfan-induced cell death. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of the environment on reproductive health.

PubMed

1991-01-01

The WHO workshop on the impact of the environment on reproductive health is summarized. Topics include the nature of environmental factors affecting reproductive health, environmental factors blamed for declining sperm quantity and quality, the effects of natural and man-made disasters on reproductive health, chemical pollutants, how the environment damages reproductive health, and research needs for better research methodologies and surveillance data. Recommendations are made to: 1) promote international research collaboration with an emphasis on consistency of methodological approaches for assessing developmental and reproductive toxicity, on development of improved surveillance systems and data bases, an strengthening international disaster alert and evaluation systems; 2) promote research capabilities for multidisciplinary studies, for interactive studies of the environment and cellular processes, and for expansion of training and education; and 3) take action on priority problems of exposure to chemical, physical, and biological agents, of exposure to pesticides among specific populations, and of inadequate screening methods for identification of environmental chemicals. The costs of environmental injury to reproduction include subfertility, intrauterine growth retardation, spontaneous abortion, and various birth defects. Developed country's primary threats are from chemical pollution, radiation, and stress. There is a large gap in knowledge. Caution is urged in understanding the direct relationship between environmental causes and infertility. Sexual health is difficult to assess and research is suggested. Exposure to excessive vitamin A and toxic chemicals are cited as agents probably having serious effects on malformations. Sperm quality has declined over the decades; there is speculation about the potential causes. The effects of radiation such as at Chernobyl are described. Toxic chemical exposure such as in Bhopal, India killed thousands. Neurological damage is reported for fetuses and infants exposed to methyl mercury. There is the beginning of evidence that complications of pregnancy may be related to pollution levels surrounding industrial plants. Reproductive health is affected through chromosome damage and cell destruction, prenatal death, altered growth, fetal abnormalities, postnatal death, functional learning deficits, and premature aging.

Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes

PubMed Central

Kirchner, Séverine; Kieu, Tiffany; Chow, Connie; Casey, Stephanie; Blumberg, Bruce

2010-01-01

The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARγ activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARγ antagonists, suggesting that activation of PPARγ mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARγ target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time. PMID:20160124

Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes.

PubMed

Kirchner, Séverine; Kieu, Tiffany; Chow, Connie; Casey, Stephanie; Blumberg, Bruce

2010-03-01

The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARgamma). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARgamma activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARgamma antagonists, suggesting that activation of PPARgamma mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARgamma target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time.

Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

PubMed Central

Chamard-Jovenin, Clémence; Thiebaut, Charlène; Chesnel, Amand; Bresso, Emmanuel; Morel, Chloé; Smail-Tabbone, Malika; Devignes, Marie-Dominique; Boukhobza, Taha; Dumond, Hélène

2017-01-01

Fetal and neonatal exposure to long-chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic (4-nonylphenol + 4-tert-octylphenol) mixture. Transcriptome and cell-phenotype analyses combined to functional and signaling network modeling indicated that long-chain alkylphenols triggered enhanced proliferation, migration ability, and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor alpha 36 (ERα36) variant. A male mouse-inherited transgenerational model of exposure to three environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1–F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatments combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low-dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility. PMID:29109696

Prenatal arsenic exposure alters REST/NRSF and microRNA regulators of embryonic neural stem cell fate in a sex-dependent manner

PubMed Central

Tyler, Christina R.; Labrecque, Matthew T.; Solomon, Elizabeth R.; Guo, Xun; Allan, Andrea M.

2016-01-01

Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50 ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs). Early in development (embryonic day 14), we observed increased expression of Rest, its co-repressor, CoREST, and the inhibitory RNA binding/splicing protein, Ptbp1, and altered expression of mRNA spliced isoforms of Pbx1 that are directly regulated by these factors in the male brain in response to prenatal 50 ppb arsenic exposure. These increases were concurrent with decreased expression of microRNA-9 (miR-9), miR-9*, and miR-124, all of which are REST/NRSF targets and inversely regulate Rest expression to allow for maturation of NSCs. Exposure to arsenic decreased the formation of neuroblasts in vitro from NSCs derived from male pup brains. The female response to arsenic was limited to increased expression of CoREST and Ptbp2, an RNA binding protein that allows for appropriate splicing of genes involved in the progression of neurogenesis. These changes were accompanied by increased neuroblast formation in vitro from NSCs derived from female pups. Unexposed male mice express transcriptomic factors to induce differentiation earlier in development compared to unexposed females. Thus, arsenic exposure likely delays differentiation of NSCs in males while potentially inducing precocious differentiation in females early in development. These effects are mitigated by embryonic day 18 of development. Arsenic-induced dysregulation of the regulatory loop formed by REST/NRSF, its target microRNAs, miR-9 and miR-124, and RNA splicing proteins, PTBP1 and 2, leads to aberrant programming of NSC function that is perhaps perpetuated into adulthood inducing deficits in differentiation we have previously observed. PMID:27751817

Violent aggression predicted by multiple pre-adult environmental hits.

PubMed

Mitjans, Marina; Seidel, Jan; Begemann, Martin; Bockhop, Fabian; Moya-Higueras, Jorge; Bansal, Vikas; Wesolowski, Janina; Seelbach, Anna; Ibáñez, Manuel Ignacio; Kovacevic, Fatka; Duvar, Oguzhan; Fañanás, Lourdes; Wolf, Hannah-Ulrike; Ortet, Generós; Zwanzger, Peter; Klein, Verena; Lange, Ina; Tänzer, Andreas; Dudeck, Manuela; Penke, Lars; van Elst, Ludger Tebartz; Bittner, Robert A; Schmidmeier, Richard; Freese, Roland; Müller-Isberner, Rüdiger; Wiltfang, Jens; Bliesener, Thomas; Bonn, Stefan; Poustka, Luise; Müller, Jürgen L; Arias, Bárbara; Ehrenreich, Hannelore

2018-05-24

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

Gene-environment interactions in the aetiology of systemic lupus erythematosus.

PubMed

Jönsen, Andreas; Bengtsson, Anders A; Nived, Ola; Truedsson, Lennart; Sturfelt, Gunnar

2007-12-01

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutation S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.

Liver histopathology in Baltic eelpout (Zoarces viviparus) - A baseline study for use in marine environmental monitoring.

PubMed

Fricke, Nicolai F; Stentiford, Grant D; Feist, Stephen W; Lang, Thomas

2012-12-01

The use of liver histopathology in various fish species as a biomarker in marine monitoring programmes to assess the biological effect of exposure to anthropogenic contaminants is well established. However, although the eelpout (Zoarces viviparus) has repeatedly been recommended as an appropriate bioindicator for monitoring purposes in the Baltic Sea, information on histopathological liver alterations of this species is scarce. In order to obtain an overview, a total of 1070 eelpout, collected in the period between spring 2001 and winter 2010 from 34 sampling sites distributed over large parts of the Baltic Sea, were histologically analyzed. Liver lesions were recorded and classified according to established liver lesion categories. A high prevalence of non-specific and early toxicopathic non-neoplastic hepatic lesions was recorded. In contrast, pre-neoplastic lesions were observed only in rare cases and neoplastic changes were absent. A comparison with published data on other fish species revealed that the observed alterations may indicate effects of environmental stressors including contaminants. The results of the present study, thus, support the application of eelpout liver histopathology in environmental monitoring. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alterations in gonadotropin secretion and ovarian function in prepubertal gilts by elevated environmental temperature.

PubMed

Flowers, B; Day, B N

1990-03-01

The effect of chronic exposure to elevated environmental temperature on gonadotropin secretion and ovarian function was studied in prepubertal gilts. Gilts were maintained under control (15.6 degrees C) or elevated temperature (33.3 degrees C) conditions from 150 to 180 days of age. Endocrine and ovarian responses to bilateral (BLO), unilateral (ULO), and sham ovariectomy were evaluated between 175 and 180 days of age. During the 96-h sampling period after BLO, plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed in heat-stressed females. Similarly, elevated temperatures abolished the transient rise in FSH and subsequent follicular growth normally associated with ULO. In contrast, environmental treatment had no effect on the secretion of FSH and LH after sham ovariectomy, yet the number of small follicles was lower in gilts exposed to elevated temperatures than in females maintained under control conditions. These results indicate that a chronic exposure to elevated environmental temperature during pubertal development diminished the ability of the hypothalamo-hypophyseal axis to secrete FSH and LH, which had physiological consequences on follicular growth. When provided an appropriate stimulus (ULO), an acute period of FSH secretion and subsequent development of follicles failed to occur in females exposed to elevated temperatures. Consequently, we propose that delayed puberty in gilts during periods of elevated environmental temperatures is due, in part, to a diminished capacity for gonadotropin secretion.

Exposure science in an age of rapidly changing climate: challenges and opportunities

PubMed Central

LaKind, Judy S; Overpeck, Jonathan; Breysse, Patrick N; Backer, Lorrie; Richardson, Susan D; Sobus, Jon; Sapkota, Amir; Upperman, Crystal R; Jiang, Chengsheng; Beard, C Ben; Brunkard, J M; Bell, Jesse E; Harris, Ryan; Chretien, Jean-Paul; Peltier, Richard E; Chew, Ginger L; Blount, Benjamin C

2016-01-01

Climate change is anticipated to alter the production, use, release, and fate of environmental chemicals, likely leading to increased uncertainty in exposure and human health risk predictions. Exposure science provides a key connection between changes in climate and associated health outcomes. The theme of the 2015 Annual Meeting of the International Society of Exposure Science—Exposures in an Evolving Environment—brought this issue to the fore. By directing attention to questions that may affect society in profound ways, exposure scientists have an opportunity to conduct “consequential science”—doing science that matters, using our tools for the greater good and to answer key policy questions, and identifying causes leading to implementation of solutions. Understanding the implications of changing exposures on public health may be one of the most consequential areas of study in which exposure scientists could currently be engaged. In this paper, we use a series of case studies to identify exposure data gaps and research paths that will enable us to capture the information necessary for understanding climate change-related human exposures and consequent health impacts. We hope that paper will focus attention on under-developed areas of exposure science that will likely have broad implications for public health. PMID:27485992

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.

PubMed

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). No significant differences in morphological characteristics were observed in any of the treatment groups (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.

Tributyltin Exposure Alters Cytokine Levels in Mouse Serum

PubMed Central

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

Tributyltin exposure alters cytokine levels in mouse serum.

PubMed

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.

Differential protein folding and chemical changes in lung tissues exposed to asbestos or particulates

PubMed Central

Pascolo, Lorella; Borelli, Violetta; Canzonieri, Vincenzo; Gianoncelli, Alessandra; Birarda, Giovanni; Bedolla, Diana E.; Salomé, Murielle; Vaccari, Lisa; Calligaro, Carla; Cotte, Marine; Hesse, Bernhard; Luisi, Fernando; Zabucchi, Giuliano; Melato, Mauro; Rizzardi, Clara

2015-01-01

Environmental and occupational inhalants may induce a large number of pulmonary diseases, with asbestos exposure being the most risky. The mechanisms are clearly related to chemical composition and physical and surface properties of materials. A combination of X-ray fluorescence (μXRF) and Fourier Transform InfraRed (μFTIR) microscopy was used to chemically characterize and compare asbestos bodies versus environmental particulates (anthracosis) in lung tissues from asbestos exposed and control patients. μXRF analyses revealed heterogeneously aggregated particles in the anthracotic structures, containing mainly Si, K, Al and Fe. Both asbestos and particulates alter lung iron homeostasis, with a more marked effect in asbestos exposure. μFTIR analyses revealed abundant proteins on asbestos bodies but not on anthracotic particles. Most importantly, the analyses demonstrated that the asbestos coating proteins contain high levels of β-sheet structures. The occurrence of conformational changes in the proteic component of the asbestos coating provides new insights into long-term asbestos effects. PMID:26159651

Environmentally realistic concentrations of the antibiotic Trimethoprim affect haemocyte parameters but not antioxidant enzyme activities in the clam Ruditapes philippinarum.

PubMed

Matozzo, Valerio; De Notaris, Chiara; Finos, Livio; Filippini, Raffaella; Piovan, Anna

2015-11-01

Several biomarkers were measured to evaluate the effects of Trimethoprim (TMP; 300, 600 and 900 ng/L) in the clam Ruditapes philippinarum after exposure for 1, 3 and 7 days. The actual TMP concentrations were also measured in the experimental tanks. The total haemocyte count significantly increased in 7 day-exposed clams, whereas alterations in haemocyte volume were observed after 1 and 3 days of exposure. Haemocyte proliferation was increased significantly in animals exposed for 1 and 7 days, whereas haemocyte lysate lysozyme activity decreased significantly after 1 and 3 days. In addition, TMP significantly increased haemolymph lactate dehydrogenase activity after 3 and 7 days. Regarding antioxidant enzymes, only a significant time-dependent effect on CAT activity was recorded. This study demonstrated that environmentally realistic concentrations of TMP affect haemocyte parameters in clams, suggesting that haemocytes are a useful cellular model for the assessment of the impact of TMP on bivalves. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

PubMed

Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C; Xi, Chuanwu

2016-06-01

Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Arsenic, asbestos and radon: emerging players in lung tumorigenesis

PubMed Central

2012-01-01

The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards. PMID:23173984

Perinatal stress and early life programming of lung structure and function

PubMed Central

Wright, Rosalind J.

2010-01-01

Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice

PubMed Central

Stephenson, Erin J.; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R.; Parvathareddy, Jyothi; Peloquin, Matthew J.; Saravia, Jordy; Han, Joan C.; Cormier, Stephania A.

2016-01-01

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle. PMID:27117006

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice.

PubMed

Stephenson, Erin J; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R; Parvathareddy, Jyothi; Peloquin, Matthew J; Saravia, Jordy; Han, Joan C; Cormier, Stephania A; Bridges, Dave

2016-06-01

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle. Copyright © 2016 the American Physiological Society.

From the Cover: Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Decreased p-β-Cateninser675 Expression and Its Interaction With E-Cadherin in the Mammary Glands of Lactating Rats.

PubMed

Dianati, Elham; Wade, Michael G; Hales, Barbara F; Robaire, Bernard; Plante, Isabelle

2017-09-01

Proper mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-catSer675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-catSer675 co-localized with β-catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering mammary gland signaling. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.