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Children are particularly vulnerable to many classes of the volatile organic compounds (VOCs) detected in indoor environments. The negative health impacts associated with chronic and acute exposures of the VOCs might lead to health issues such as genetic damage, cancer, and disorder of nervous systems. In this study, 40 VOCs including aldehydes and ketones, aliphatic hydrocarbons, esters, aromatic hydrocarbons, cyclic terpenes, alcohols, and glycol ethers were identified and qualified in different locations at the University of Missouri (MU) Child Development Laboratory (CDL) in Columbia, Missouri. Our results suggested that the concentrations of the VOCs varied significantly among classrooms, hallways, and playground. The VOCs emitted from personal care and cleaning products had the highest indoor levels (2-ethylhexanol-1, 3-carene, homomenthyl salicylate with mean concentration of 5.15 µg/m3 , 1.57 µg/m3 , and 1.47 µg/m3 , respectively). A cancer risk assessment was conducted, and none of the 95th percentile dose estimates exceeded the age-specific no significant risk levels (NSRL) in all classrooms. Dimensionless toxicity index scores were calculated for all VOCs using a novel web-based framework called Toxicological Prioritization Index (ToxPi), which integrates multiple sources of toxicity data. According to the method, homomenthyl salicylate, benzothiazole, 2-ethylhexyl salicylate, hexadecane, and tridecane exhibited diverse toxicity profiles and ranked as the five most toxic indoor VOCs. The findings of this study provide critical information for policy makers and early education professionals to mitigate the potentially negative health impacts of indoor VOCs in the childcare facilities.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Criança , Monitoramento Ambiental , Humanos , Medição de Risco , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/toxicidadeRESUMO
Unconventional oil and natural gas (UOG) operations couple horizontal drilling with hydraulic fracturing to access previously inaccessible fossil fuel deposits. Hydraulic fracturing, a common form of stimulation, involves the high-pressure injection of water, chemicals, and sand to fracture the target layer and release trapped natural gas and/or oil. Spills and/or discharges of wastewater have been shown to impact surface, ground, and drinking water. The goals of this study were to characterize the endocrine activities and measure select organic contaminants in groundwater from conventional oil and gas (COG) and UOG production regions of Wyoming. Groundwater samples were collected from each region, solid-phase extracted, and assessed for endocrine activities (estrogen, androgen, progesterone, glucocorticoid, and thyroid receptor agonism and antagonism), using reporter gene assays in human endometrial cells. Water samples from UOG and conventional oil areas exhibited greater ER antagonist activities than water samples from conventional gas areas. Samples from UOG areas tended to exhibit progesterone receptor antagonism more often, suggesting there may be a UOG-related impact on these endocrine activities. We also report UOG-specific contaminants in Pavillion groundwater extracts, and these same chemicals at high concentrations in a local UOG wastewater sample. A unique suite of contaminants was observed in groundwater from a permitted drinking water well at a COG well pad and not at any UOG sites; high levels of endocrine activities (most notably, maximal estrogenic activity) were noted there, suggesting putative impacts on endocrine bioactivities by COG. As such, we report two levels of evidence for groundwater contamination by both UOG and COG operations in Wyoming.
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Disruptores Endócrinos/análise , Água Subterrânea/análise , Campos de Petróleo e Gás , Poluentes Químicos da Água/análise , Linhagem Celular , Disruptores Endócrinos/toxicidade , Endométrio/citologia , Monitoramento Ambiental , Feminino , Água Subterrânea/química , Humanos , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Progesterona/antagonistas & inibidores , Testes de Toxicidade/métodos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/toxicidade , Águas Residuárias/química , Poluentes Químicos da Água/toxicidade , WyomingRESUMO
CORRECTION: After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".
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A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.
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Conferências de Consenso como Assunto , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Substâncias Perigosas/efeitos adversos , Congressos como Assunto , Diabetes Mellitus/induzido quimicamente , Humanos , Itália , Síndrome Metabólica/induzido quimicamente , Obesidade/induzido quimicamenteRESUMO
Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered.
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Poluentes Ocupacionais do Ar/farmacologia , Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Etinilestradiol/farmacologia , Fenóis/farmacologia , Desenvolvimento Sexual/efeitos dos fármacos , Animais , Animais Selvagens , Poluição Ambiental , Estrogênios/farmacologia , Feminino , MasculinoRESUMO
Unconventional oil and gas (UOG) operations have the potential to increase air and water pollution in communities located near UOG operations. Every stage of UOG operation from well construction to extraction, operations, transportation, and distribution can lead to air and water contamination. Hundreds of chemicals are associated with the process of unconventional oil and natural gas production. In this work, we review the scientific literature providing evidence that adult and early life exposure to chemicals associated with UOG operations can result in adverse reproductive health and developmental effects in humans. Volatile organic compounds (VOCs) [including benzene, toluene, ethyl benzene, and xylene (BTEX) and formaldehyde] and heavy metals (including arsenic, cadmium and lead) are just a few of the known contributors to reduced air and water quality that pose a threat to human developmental and reproductive health. The developing fetus is particularly sensitive to environmental factors, which include air and water pollution. Research shows that there are critical windows of vulnerability during prenatal and early postnatal development, during which chemical exposures can cause potentially permanent damage to the growing embryo and fetus. Many of the air and water pollutants found near UOG operation sites are recognized as being developmental and reproductive toxicants; therefore there is a compelling need to increase our knowledge of the potential health consequences for adults, infants, and children from these chemicals through rapid and thorough health research investigation.
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Gás Natural , Reprodução/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos , Disruptores Endócrinos/toxicidade , Exposição Ambiental , Feminino , Humanos , Masculino , Metais Pesados/toxicidade , Gravidez , Compostos Orgânicos Voláteis/toxicidade , Águas ResiduáriasRESUMO
Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE(2)) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 µg/kg/day, BPA, 10 µg/kg/day, EE(2), 0.01, 0.1, or 1.0 µg/kg/day, or vehicle from Gestation Day 11 to Postnatal Day 12 via a mini-osmotic pump in the dam. Developmental Xenoestrogen exposure altered femoral geometry and strength, assessed in adulthood by micro-computed tomography and torsional strength analysis, respectively. Low-dose EE(2), DES, or BPA increased adult femur length. Exposure to the highest dose of EE(2) did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE(2) and DES but not BPA decreased tensile strength. The combined effect of increased femur length and decreased tensile strength resulted in a trend toward decreased torsional ultimate strength and energy to failure. Taken together, these results suggest that exposure to developmental exposure to environmentally relevant levels of xenoestrogens may negatively impact bone length and strength in adulthood.
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Dietilestilbestrol/farmacologia , Etinilestradiol/farmacologia , Fêmur/anatomia & histologia , Fêmur/embriologia , Desenvolvimento Fetal/efeitos dos fármacos , Fenóis/farmacologia , Resistência à Tração/efeitos dos fármacos , Administração Oral , Animais , Compostos Benzidrílicos , Fenômenos Biomecânicos , Colágeno/metabolismo , Dietilestilbestrol/administração & dosagem , Relação Dose-Resposta a Droga , Etinilestradiol/administração & dosagem , Feminino , Fêmur/efeitos dos fármacos , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Fenóis/administração & dosagem , GravidezRESUMO
Human and rat endometriotic lesions synthesize and secrete tissue inhibitor of metalloproteinase 1 (TIMP1). More TIMP1 localizes in the ovarian theca in an established rat model for endometriosis (Endo) when compared to surgical controls (Sham). We hypothesized that endometriotic TIMP1 secreted into peritoneal fluid (PF) negatively affects ovarian function and embryogenesis by altering the balance of matrix metalloproteinases (MMPs) and TIMPs. Three experiments were performed modulating TIMP1 in vitro and in vivo to investigate ovarian and embryonic anomalies. The first experiment demonstrated control embryos treated in vitro with endometriotic PF concentrations of TIMP1 developed abnormally. In the second experiment where TIMP1 was modulated in vivo, TIMP1-treated Sham rats had fewer zygotes, ovarian follicles, and corpora lutea (CLs) and poorer embryo quality and development, which is analogous to the findings in Endo rats. Importantly, Endo rats treated with a TIMP1 function-blocking antibody had zygote, follicle, and CL numbers and embryo quality similar to Sham rats. In addition, more TIMP1 inhibitory activity was found in ovaries from Endo and TIMP1-treated Sham rats than in ovaries from Sham or TIMP1 antibody-treated Endo rats. In experiment three, control rats (no surgery) treated with Endo PF had fewer follicles and CLs and increased TIMP1 localization in the ovarian theca whereas treatment with Endo PF stripped of TIMP1 or with Sham PF had no effect, providing further evidence that endometriotic TIMP1 sequesters in the ovary and inhibits MMPs necessary for ovulation. Collectively, these results showed that excessive TIMP1 was deleterious to ovulation and embryo development. Thus, novel TIMP1-modulating therapies may be developed to alleviate infertility in women with endometriosis.
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Desenvolvimento Embrionário/efeitos dos fármacos , Endometriose/metabolismo , Infertilidade Feminina/terapia , Ovário/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Animais , Anticorpos/farmacologia , Líquido Ascítico/química , Corpo Lúteo/efeitos dos fármacos , Modelos Animais de Doenças , Técnicas de Cultura Embrionária , Endometriose/complicações , Feminino , Infertilidade Feminina/etiologia , Inibidores de Metaloproteinases de Matriz , Folículo Ovariano/efeitos dos fármacos , Ovário/química , Ovário/fisiopatologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/análise , Zigoto/efeitos dos fármacosRESUMO
This study develops a measure of perceived authenticity in science communication and then explores communication strategies to improve the perceived authenticity of a scientific message. The findings are consistent with literature around trust and credibility, but indicate that authenticity-the perception that the scientist is a unique individual with qualities beyond institutional affiliations or a role in the production of the research-may add a potentially important dimension to accepted categories of integrity and benevolence.
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Comunicação , Narração , Ciência , Confiança , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Adulto JovemRESUMO
Endometriosis is a complex and high impact disease affecting 176 million women worldwide with diagnostic latency between 4 to 11 years due to lack of a definitive clinical symptom or a minimally invasive diagnostic method. In this study, we developed a new ensemble machine learning classifier based on chromosomal partitioning, named GenomeForest and applied it in classifying the endometriosis vs. the control patients using 38 RNA-seq and 80 enrichment-based DNA-methylation (MBD-seq) datasets, and computed performance assessment with six different experiments. The ensemble machine learning models provided an avenue for identifying several candidate biomarker genes with a very high F1 score; a near perfect F1 score (0.968) for the transcriptomics dataset and a very high F1 score (0.918) for the methylomics dataset. We hope in the future a less invasive biopsy can be used to diagnose endometriosis using the findings from such ensemble machine learning classifiers, as demonstrated in this study.
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The rise of hydraulic fracturing and unconventional oil and gas (UOG) exploration in the United States has increased public concerns for water contamination induced from hydraulic fracturing fluids and associated wastewater spills. Herein, we collected surface and groundwater samples across Garfield County, Colorado, a drilling-dense region, and measured endocrine bioactivities, geochemical tracers of UOG wastewater, UOG-related organic contaminants in surface water, and evaluated UOG drilling production (weighted well scores, nearby well count, reported spills) surrounding sites. Elevated antagonist activities for the estrogen, androgen, progesterone, and glucocorticoid receptors were detected in surface water and associated with nearby shale gas well counts and density. The elevated endocrine activities were observed in surface water associated with medium and high UOG production (weighted UOG well score-based groups). These bioactivities were generally not associated with reported spills nearby, and often did not exhibit geochemical profiles associated with UOG wastewater from this region. Our results suggest the potential for releases of low-saline hydraulic fracturing fluids or chemicals used in other aspects of UOG production, similar to the chemistry of the local water, and dissimilar from defined spills of post-injection wastewater. Notably, water collected from certain medium and high UOG production sites exhibited bioactivities well above the levels known to impact the health of aquatic organisms, suggesting that further research to assess potential endocrine activities of UOG operations is warranted.
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Água Subterrânea , Fraturamento Hidráulico , Poluentes Químicos da Água , Colorado , Gás Natural , Campos de Petróleo e Gás , Estados Unidos , Águas Residuárias , Poluentes Químicos da Água/análise , Recursos HídricosRESUMO
Previous studies conducted in our laboratory have found altered adult health outcomes in animals with prenatal exposure to environmentally relevant levels of unconventional oil and gas (UOG) chemicals with endocrine-disrupting activity. This study aimed to examine potential metabolic health outcomes following a preconception, prenatal and postnatal exposure to a mixture of 23 UOG chemicals. Prior to mating and from gestation day 1 to postnatal day 21, C57BL/6J mice were developmentally exposed to a laboratory-created mixture of 23 UOG chemicals in maternal drinking water. Body composition, spontaneous activity, energy expenditure, and glucose tolerance were evaluated in 7-month-old female offspring. Neither body weight nor body composition differed in 7-month female mice. However, females exposed to 1.5 and 150 µg/kg/day UOG mix had lower total and resting energy expenditure within the dark cycle. In the light cycle, the 1,500 µg//kg/day group had lower total energy expenditure and the 1.5 µg/kg/day group had lower resting energy expenditure. Females exposed to the 150 µg/kg/day group had lower spontaneous activity in the dark cycle, and females exposed to the 1,500 µg/kg/day group had lower activity in the light cycle. This study reports for the first time that developmental exposure to a mixture of 23 UOG chemicals alters energy expenditure and spontaneous activity in adult female mice.
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Endometriosis is a complex and common gynecological disorder yet a poorly understood disease affecting about 176 million women worldwide and causing significant impact on their quality of life and economic burden. Neither a definitive clinical symptom nor a minimally invasive diagnostic method is available, thus leading to an average of 4 to 11 years of diagnostic latency. Discovery of relevant biological patterns from microarray expression or next generation sequencing (NGS) data has been advanced over the last several decades by applying various machine learning tools. We performed machine learning analysis using 38 RNA-seq and 80 enrichment-based DNA methylation (MBD-seq) datasets. We experimented how well various supervised machine learning methods such as decision tree, partial least squares discriminant analysis (PLSDA), support vector machine, and random forest perform in classifying endometriosis from the control samples trained on both transcriptomics and methylomics data. The assessment was done from two different perspectives for improving classification performances: a) implication of three different normalization techniques and b) implication of differential analysis using the generalized linear model (GLM). Several candidate biomarker genes were identified by multiple machine learning experiments including NOTCH3, SNAPC2, B4GALNT1, SMAP2, DDB2, GTF3C5, and PTOV1 from the transcriptomics data analysis and TRPM6, RASSF2, TNIP2, RP3-522J7.6, FGD3, and MFSD14B from the methylomics data analysis. We concluded that an appropriate machine learning diagnostic pipeline for endometriosis should use TMM normalization for transcriptomics data, and quantile or voom normalization for methylomics data, GLM for feature space reduction and classification performance maximization.
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Background Understanding the role of environmental toxicant exposure on children's development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children's exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited. Objectives The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children's cognitive, socioemotional, and behavioral development among young children. Methods This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children's development across multiple domains. Results The results highlight the potential risk of exposure to multiple environmental toxicants for young children's cognitive and socioemotional development. Discussion Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.
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Sucesso Acadêmico , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Substâncias Perigosas/efeitos adversos , Criança , Pré-Escolar , Emoções , Exposição Ambiental/classificação , Feminino , Substâncias Perigosas/classificação , Humanos , Lactente , Recém-Nascido , Masculino , Comportamento SocialRESUMO
The contamination of surface water and ground water by human activities, such as fossil fuel extraction and agriculture, can be difficult to assess due to incomplete knowledge of the chemicals and chemistry involved. This is particularly true for the potential contamination of drinking water by nearby extraction of oil and/or gas from wells completed by hydraulic fracturing. A case that has attracted considerable attention is unconventional natural gas extraction in Susquehanna County, Pennsylvania, particularly around Dimock, Pennsylvania. We analyzed surface water and groundwater samples collected throughout Susquehanna County with complementary biological assays and high-resolution mass spectrometry. We found that Ah receptor activity was associated with proximity to impaired gas wells. We also identified certain chemicals, including disclosed hydraulic fracturing fluid additives, in samples that were either in close proximity to impaired gas wells or that exhibited a biological effect. In addition to correlations with drilling activity, the biological assays and high-resolution mass spectrometry detected substances that arose from other anthropogenic sources. Our complementary approach provides a more comprehensive picture of water quality by considering both biological effects and a broad screening for chemical contaminants.
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Monitoramento Ambiental/métodos , Fraturamento Hidráulico , Poluentes Químicos da Água/análise , Bioensaio , Linhagem Celular Tumoral , Cromatografia Líquida , Água Doce/análise , Humanos , Espectrometria de Massas , Campos de Petróleo e Gás , Pennsylvania , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Esteroides/metabolismo , Poluentes Químicos da Água/farmacologiaRESUMO
Chemicals used in unconventional oil and gas (UOG) operations can act as endocrine disrupting chemicals and metabolic disruptors. Our lab has reported altered energy expenditure and activity in C57BL/6J mice that were preconceptionally, gestationally, and lactationally exposed via maternal drinking water to a laboratory-created mixture of 23 UOG chemicals from gestational day 1 to postnatal day 21 in 7-month-old female mice with no change in body composition. We hypothesized that allowing the mice to age and exposing them to a high fat, high sugar diet might reveal underlying changes in energy balance. To investigate whether aging and metabolic challenge would exacerbate this phenotype, these mice were aged to 12 months and given a high fat, high sugar diet (HFHSD) challenge. The short 3-day HFHSD challenge increased body weight and fasting blood glucose in all mice. Developmental exposure to the 23 UOG mixture was associated with increased activity and non-resting energy expenditure in the light cycle, increased exploratory behavior in the elevated plus maze test, and decreased sleep in 12 month female mice. Each of these effects was seen in the light cycle when mice are normally less active. Further studies are needed to better understand the behavioral changes observed after developmental exposure to UOG chemicals.
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Unconventional oil and natural gas (UOG) operations have contributed to a surge in domestic oil and natural gas production in the United States, combining horizontal drilling with hydraulic fracturing to unlock previously inaccessible fossil fuel deposits. >1000 organic chemicals are used in the production process, and wastewater is produced following injection and for the life of the producing well. This wastewater is typically disposed of via injecting into disposal wells for long-term storage, treatment and discharge from wastewater treatment plants, and/or storage in open evaporation pits; however, wastewater spill rates are reported at 2-20% of active well sites across regions, increasing concerns about the environmental impacts of these wastewaters. This study assessed adipogenic activity (both triglyceride accumulation and pre-adipocyte proliferation) for a mixture of 23 commonly used UOG chemicals and a small subset of UOG wastewater-impacted surface water extracts from Colorado and West Virginia, using 3T3-L1 cells and a peroxisome proliferator activated receptor gamma (PPARγ) reporter assay. We report potent and efficacious adipogenic activity induced by both a laboratory-created UOG chemical mixture and UOG-impacted water samples at concentrations below environmental levels. We further report activation of PPARγ at similar concentrations for some samples, suggesting a causative molecular pathway for the observed effects, but not for other adipogenic samples, implicating PPARγ-dependent and independent effects from UOG associated chemicals. Taken together, these results suggest that UOG wastewater has the potential to impact metabolic health at environmentally relevant concentrations.
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Testes de Toxicidade , Águas Residuárias/toxicidade , Poluentes Químicos da Água/toxicidade , Células 3T3-L1 , Adipogenia , Animais , Colorado , Meio Ambiente , Monitoramento Ambiental , Fraturamento Hidráulico , Camundongos , Gás Natural , Campos de Petróleo e Gás , PPAR gama , Poluição por Petróleo , Água , West VirginiaRESUMO
Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 µg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 µg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 µg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies.
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Disruptores Endócrinos/toxicidade , Fraturamento Hidráulico/métodos , Glândulas Mamárias Animais/crescimento & desenvolvimento , Indústria de Petróleo e Gás/métodos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Apoptose , Exposição Ambiental , Feminino , Idade Gestacional , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Lactação , Glândulas Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Maturidade SexualRESUMO
There is evidence from longitudinal studies that being light at birth and weaning is associated with subsequent rapid weight gain in infants. This is referred to as "centile crossing", which can lead to increased risk of lifetime obesity, glucose dysregulation and type 2 diabetes. Here, pregnant CD-1 mice were hemi-ovariectomized so that the entire litter was contained in one uterine horn to increase variability in fetal growth rate. Pregnant females were implanted on gestation day (GD) 9 with a Silastic capsule containing 6, 60 or 600 µg bisphenol A (BPA). On GD 18 the mean fetal serum unconjugated BPA concentrations were 17, 177 and 1858 pg/ml, respectively. Capsules were not removed, to avoid maternal stress, and were predicted to release BPA for at least 3 weeks. Body weight at weaning was strongly negatively correlated with post-weaning weight gain in both control and BPA-treated male mice, consistent with human data; female offspring were excluded, avoiding complications associated with postpubertal estrogens. Within each treatment group, male offspring were sorted into tertiles based on relative weight gain during the two weeks after weaning, designated as having Rapid (R), Medium (M) or Slow (S) growth rate. BPA exposure was associated with altered growth rate between weaning and postnatal week 12 (young adulthood), when a low-dose (20 mg/kg, i.p.) glucose tolerance test (GTT) was performed. We found altered glucose regulation in response to all doses of BPA. However, glucose tolerance was only significantly impaired (blood glucose levels were elevated) compared to controls in males in the rapid post-weaning growth group exposed perinatally to BPA. We conclude that male mice that are light at weaning, but then experience rapid catch-up growth immediately after weaning, represent a sensitive sub-population that is vulnerable to the metabolic disrupting effects of very low pg/ml fetal serum concentrations of BPA.
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Compostos Benzidrílicos/farmacologia , Peso Corporal/efeitos dos fármacos , Intolerância à Glucose/sangue , Fenóis/farmacologia , Aumento de Peso/efeitos dos fármacos , Animais , Compostos Benzidrílicos/sangue , Feminino , Teste de Tolerância a Glucose , Masculino , Camundongos , Fenóis/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , DesmameRESUMO
Chemicals associated with unconventional oil and gas (UOG) operations have been shown to contaminate surface and ground water with a variety of endocrine disrupting compounds (EDCs) inducing multiple developmental alteration in mice. However, little is known about the impacts of UOG-associated contaminants on amphibian health and resistance to an emerging ranavirus infectious disease caused by viruses in the genus Ranavirus, especially at the vulnerable tadpole stage. Here we used tadpoles of the amphibian Xenopus laevis and the ranavirus Frog virus 3 (FV3) as a model relevant to aquatic environment conservation research for investigating the immunotoxic effects of exposure to a mixture of 23 UOG-associated chemicals with EDC activity. Xenopus tadpoles were exposed to an equimass mixture of 23 UOG-associated chemicals (range from 0.1 to 10 µg/l) for 3 weeks prior to infection with FV3. Our data show that exposure to the UOG chemical mixture is toxic for tadpoles at ecological doses of 5 to 10 µg/l. Lower doses significantly altered homeostatic expression of myeloid lineage genes and compromised tadpole responses to FV3 through expression of TNF-α, IL-1ß, and Type I IFN genes, correlating with an increase in viral load. Exposure to a subset of 6 UOG chemicals was still sufficient to perturb the antiviral gene expression response. These findings suggest that UOG-associated water pollutants at low but environmentally relevant doses have the potential to induce acute alterations of immune function and antiviral immunity.