RESUMO
In recent decades, there has been a consistent decline in semen quality across the globe, with environmental pollution emerging as the predominant factor. Persistent organic pollutants (POPs) have garnered considerable attention due to their potent biological toxicity and resistance to natural degradation. Within this class of pollutants, polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) have been identified as detrimental agents that can disrupt cellular physiological functions by activating aryl hydrocarbon receptor (AhR). However, the precise role of AhR in the adverse effects of environmental pollutants on male mammalian fertility remains incompletely understood. This article provides a comprehensive review of the impact of various environmental pollutants, specifically PAHs such as benzo[a]pyrene, 3-methylcholanthrene, and 7,12-dimethylbenzo[a]anthracene, HAHs including 2,3,7,8-tetrachlorodibenzo-p-dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers, and the pollutant complex PM2.5, as well as cigarette smoke condensates, on male mammalian reproductive function. Additionally, this review focuses on the role of the AhR in mediating these effects. The objective of this review is to elucidate the involvement of AhR in the regulation of male mammalian fertility, thereby offering insights for prospective investigations into the interplay between AhR and male reproductive function, as well as the etiology of idiopathic male infertility in clinic.
Assuntos
Poluentes Ambientais , Infertilidade Masculina , Hidrocarbonetos Policíclicos Aromáticos , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/metabolismo , Masculino , Animais , Poluentes Ambientais/toxicidade , Poluentes Ambientais/efeitos adversos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/toxicidade , Fertilidade/efeitos dos fármacos , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/toxicidade , Poluentes Orgânicos Persistentes/efeitos adversos , Poluentes Orgânicos Persistentes/metabolismoRESUMO
Exposure to endocrine-disrupting chemicals, like Polybrominated diphenyl ethers (PBDEs), is suspected of playing a role in the occurrence of breast cancer. Moreover, there is growing evidence that food chemical contaminants, especially lipophilic ones such as PBDEs, could interact with different components of the diet. The objective of the present study was to assess the association between dietary intake of PBDEs and breast cancer risk in the French E3N cohort study, and to investigate the potential modification of this association by vegetable oil consumption. The study included 67879 women. Intakes of eight PBDEs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire, and food contamination levels measured by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES). Cox proportional hazards models were used to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) for the association between total PBDEs dietary intake and breast cancer risk. Interaction measures for vegetable oil consumption were estimated on both additive and multiplicative scales. The women were followed for a maximum of 21.4 years, and 5 686 developed an incident breast cancer. A positive linear trend was highlighted between dietary intake of PBDEs in quintile groups and breast cancer risk, borderline with statistical significance (p-trend = 0.06, HRQ5vsQ1 and 95% CI: 1.09 [0.99;1.20]). Interaction measures for vegetable oil consumption were significant in both additive and multiplicative scales. Higher effect sizes of the association were highlighted in high consumers of vegetable oil, i.e. ≥4.6 g/day (HRQ5vsQ1 and 95% CI: 1.23 [1.08; 1.40]), and almost no effect were found in low consumers (HRQ5vsQ1 and 95% CI: 0.97 [0.86; 1.10]). Highlighting such interactions between nutrients and chemicals is crucial to develop efficient dietary recommendations to limit the negative health effects associated with exposure to food chemical contaminants.
Assuntos
Neoplasias da Mama , Poluentes Ambientais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Exposição Dietética/efeitos adversos , Poluentes Ambientais/análise , Feminino , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/análise , Humanos , Óleos de Plantas/efeitos adversosRESUMO
INTRODUCTION: Post-partum depression (PPD) affects up to 19.1% of pregnancies and is associated with increased levels of proinflammatory cytokines, inflammation, and reductions in brain-derived neurotrophic factor (BDNF). Previous work by our team suggests that environmental toxins such as polybrominated diphenyl ethers (PBDEs) enhance placental inflammation and reduce BDNF production. Nearly, 100% of studied women in California have some level of exposure to these compounds due to extensive use of the flame retardants. High levels of exposure to PBDEs has been linked to increased risk of adverse pregnancy complications associated with placental inflammation such as preterm birth and gestational diabetes but their effects on risk of PPD is unclear. OBJECTIVE: To determine if PPD is associated with higher levels of PBDE-47, the most common PBDE congener in maternal plasma. METHODS: PBDE-47 was quantified in first trimester plasma samples collected from a cohort of 367 asymptomatic pregnant women that were routinely screened for depressive symptoms for 1 year post-partum. Data were analyzed using general linear models and multivariable logistic regression to determine if higher levels of PBDE-47 in the first trimester are associated with development of PPD. RESULTS: Women who developed PPD (n = 22) had significantly higher PBDE-47 levels in their plasma (p=.031) relative to those in which PPD was not diagnosed. Logistic regression analysis suggested that each two-fold increase in PBDE-47 concentrations increased the risk of PPD by 22% (OR = 1.22, 95% CI: 1.03, 1.47). Groups were similar regarding PTB rate, race-ethnicity, parity, child's sex, maternal pre-pregnancy obesity status, maternal age, family income, and study center. Results remained significant after adjustment for these possible confounding factors. CONCLUSIONS: These results suggest that PBDE-47 exposure in the first trimester is associated with increased risk of PPD.
Assuntos
Depressão Pós-Parto , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Fator Neurotrófico Derivado do Encéfalo , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Éteres Difenil Halogenados/efeitos adversos , Inflamação , Exposição Materna/efeitos adversos , Placenta , Nascimento Prematuro/induzido quimicamenteRESUMO
AIMS: We aimed to investigate the effect of PBDEs (47, 99, 209) on cellular events involved in epigenetic modification, inflammation, and epithelial mesenchymal transition (EMT). MATERIALS AND METHODS: We studied: 1) ERK1/2 phosphorylation; 2) Enhancer of Zester Homolog 2 (EZH2); 3) Histone H3 tri-methylated in lysine 27 (H3K27me3); 4) K-RAS; 5) silencing disabled homolog 2-interacting protein gene (DAB2IP), 6) let-7a; 7) Muc5AC/Muc5B, and 8) IL-8 in a 3D in vitro model of epithelium obtained with primary Normal Human Bronchial Epithelial cells (pNHBEs) or A549 cell line, chronically exposed to PBDEs (47, 99, 209). KEY FINDINGS: PBDEs (10 nM, 100 nM and 1 µM) increased ERK1/2 phosphorylation, and EZH2, H3K27me3, and K-RAS protein expression, while decreased DAB2IP and Let-7a transcripts in pNHBEs ALI culture. Furthermore PBDEs (47, 99) (100 nM) increased Muc5AC and Muc5B mRNA, and PBDE 47 (100 nM) IL-8 mRNA via EZH2 in pNHBEs. Finally, PBDEs (100 nM) affected EZH2, H3K27me3, K-RAS protein expression, and DAB2IP, Let-7a transcripts and cell invasion in A549 cells. Gsk343 (methyltransferase EZH2 inhibitor) (1 mM) and U0126 (inhibitor of MEK1/2) (10 µM) were used to show the specific effect of PBDEs. SIGNIFICANCE: PBDE inhalation might promote inflammation/cancer via EZH2 methyltransferase activity and H3K27me3, k-RAS and ERk1/2 involvement, generating adverse health outcomes of the human lung.
Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células Epiteliais , Retardadores de Chama/administração & dosagem , Éteres Difenil Halogenados/efeitos adversos , Neoplasias Pulmonares , Proteínas de Neoplasias/metabolismo , Mucosa Respiratória , Células A549 , Idoso , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Feminino , Retardadores de Chama/farmacologia , Éteres Difenil Halogenados/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Respiratória/enzimologia , Mucosa Respiratória/patologiaRESUMO
OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.
Assuntos
Éteres Difenil Halogenados , Primeiro Trimestre da Gravidez/sangue , Nascimento Prematuro , Doenças da Glândula Tireoide , Tireotropina/sangue , Adulto , Estudos de Coortes , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/análise , Disruptores Endócrinos/sangue , Feminino , Retardadores de Chama/efeitos adversos , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/sangue , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/diagnóstico , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase. METHODS: Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics. RESULTS: Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected. CONCLUSION: Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.
Assuntos
Disruptores Endócrinos/análise , Poluentes Ambientais/análise , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Secundário/epidemiologia , Glândulas Paratireoides/química , Neoplasias das Paratireoides/epidemiologia , Causalidade , Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/análise , Humanos , Hiperparatireoidismo Primário/patologia , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/patologia , Hiperparatireoidismo Secundário/cirurgia , Incidência , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/análise , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Chemical contaminants such as industrial and urban by-products, pharmaceuticals, drugs metabolites and, plastics, are continuously found in the oceans, affecting its quality and organism's welfare. Although these compounds are found at concentrations ranged ng L-1, there is an increasing concern about the potential adverse effects of the interactions among those substances present, simultaneously, in a mixture. In the present study, specimens of sea bream (Sparus aurata) were exposed, by food, to rising concentrations of a mixture of carbamazepine, polybrominated diphenyl ether-47 and cadmium chloride, for 15 days and then, maintained, with the same control diet, without contaminants, for other 15 days. Samples of skin mucus, serum, head-kidney, liver and intestine were sampled at 0, 15 and 30 days. Cellular immune parameters were evaluated on head-kidney, as well as humoral parameters were determined on skin mucus and serum. In addition, the expression of some genes, related to immunity, was analysed on liver and intestine. Both cellular and humoral response were affected at 15 days, showing slightly signs of recovery at 30 days. Besides, the expression of immune-related genes was highly affected, suggesting the development of inflammatory processes, as well as a reduction of immune parameters. Overall, the mixture of compounds severally affected the immune system of sea bream, suggesting a lower degree of recovery. The prolonged exposure to a mixture of these compounds could entail serious change on population immunity and, eventually, promote changes on marine biota.
Assuntos
Doenças dos Peixes/imunologia , Imunidade Celular , Imunidade Humoral , Inflamação/veterinária , Dourada/imunologia , Poluentes Químicos da Água/efeitos adversos , Animais , Cloreto de Cádmio/efeitos adversos , Carbamazepina/efeitos adversos , Doenças dos Peixes/induzido quimicamente , Éteres Difenil Halogenados/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/imunologiaRESUMO
BACKGROUND: Perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores. METHODS: Women included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted ß coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models. RESULTS: The highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (ß = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (ß = - 0.26, 95% CI = -0.48, - 0.04; ß = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores. DISCUSSION: Among a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.
Assuntos
Peso ao Nascer/efeitos dos fármacos , Poluentes Ambientais/efeitos adversos , Retardadores de Chama/efeitos adversos , Fluorocarbonos/efeitos adversos , Idade Gestacional , Éteres Difenil Halogenados/efeitos adversos , Exposição Materna/efeitos adversos , Adulto , Estudos de Coortes , Poluentes Ambientais/sangue , Feminino , Retardadores de Chama/metabolismo , Fluorocarbonos/sangue , Éteres Difenil Halogenados/sangue , Humanos , Gravidez , São Francisco , Adulto JovemRESUMO
BACKGROUND: Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function. METHODS: To evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods. RESULTS: PBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive). CONCLUSIONS: We found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.
Assuntos
Biomarcadores/metabolismo , Éteres Difenil Halogenados/efeitos adversos , Exposição Materna/efeitos adversos , Placenta/química , Placentação/efeitos dos fármacos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Biomarcadores/sangue , Feminino , Feto/química , Humanos , Fígado/química , Gravidez , Complicações na Gravidez/induzido quimicamente , São Francisco/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Environmental chemicals that interfere with the production and/or action of hormones may have adverse effects on male reproduction. This review focuses on the possible impact of exposure to flame retardant chemicals on male reproduction. Flame retardants are added to a wide variety of combustible materials to prevent fires from starting, slow their spread, and provide time to escape. However, these chemicals are often additive so they leach out into the environment. Governments have restricted the use of polybrominated diphenyl ether flame retardants based on evidence that they are persistent and bioaccumulate and have adverse effects on health. The phasing out of these "legacy" flame retardants has resulted in their replacement with alternatives, such as tetrabromobisphenol A and the organophosphate esters. OBJECTIVE: To review the literature on the effects of brominated and organophosphate ester flame retardant chemicals on male reproduction. METHODS: PubMed database was searched for studies reporting the effects of brominated and organophosphate ester flame retardants on male reproduction. RESULTS: Cell-based, animal model, and human studies provide evidence that the polybrominated diphenyl ethers act as endocrine-disrupting chemicals; further, exposure during critical windows of development may be associated with a permanent impact on male reproduction. In vitro and animal model data are accumulating with respect to the effects of tetrabromobisphenol A and organophosphate esters, but few studies have evaluated their impact on human health. CONCLUSIONS: More research on human exposure to replacement flame retardants and the possibility that they may be associated with adverse reproductive health outcomes is a high priority.
Assuntos
Disruptores Endócrinos/efeitos adversos , Retardadores de Chama/efeitos adversos , Genitália Masculina/efeitos dos fármacos , Animais , Bromo/efeitos adversos , Poluentes Ambientais/efeitos adversos , Éteres Difenil Halogenados/efeitos adversos , Humanos , Masculino , Organofosfatos/efeitos adversos , Bifenil Polibromatos/efeitos adversosRESUMO
Perinatal exposures to polybrominated diphenyl ethers permanently reprogram liver metabolism and induce a nonalcoholic fatty liver disease-like phenotype and insulin resistance in rodents. Aim: To test if these changes are associated with altered liver epigenome. Materials & methods: Expression of small RNA and changes in DNA methylation in livers of adult rats were analyzed following perinatal exposure to 2,2',4,4'-tetrabromodiphenyl ether, the polybrominated diphenyl ether congener most prevalent in human tissues. Results: We identified 33 differentially methylated DNA regions and 15 differentially expressed miRNAs. These changes were enriched for terms related to lipid and carbohydrate metabolism, insulin signaling, Type-2 diabetes and nonalcoholic fatty liver disease. Conclusion: Changes in the liver epigenome are a likely candidate mechanism of long-term maintenance of an aberrant metabolic phenotype.
Assuntos
Poluentes Ambientais/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Epigenoma , Éteres Difenil Halogenados/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Biomarcadores , Metabolismo dos Carboidratos/efeitos dos fármacos , Metilação de DNA , Suscetibilidade a Doenças , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/patologia , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , RatosRESUMO
Persistent organic pollutants (POPs) have been associated with a high risk of type 2 diabetes in different regions, although few studies from China have been published. We aimed to investigate the associations between POP exposure and type 2 diabetes in Chinese population. A total of 158 participants diagnosed with type 2 diabetes and 158 participants without the disorder from Shandong Province were enrolled in this case-control study during 2016-2017. Nine polychlorinated biphenyl congeners (PCBs) and 2 polybrominated diphenyl ethers with detectable levels in ≥75% of the participants were selected for data analysis. The results showed that POP exposure was significantly and positively associated with the risk of diabetes after adjusting for age, sex, BMI, triglycerides and total cholesterol. However, we did not observe an obvious modified effect of adiposity on the associations between POP exposure and diabetes in the present study, as strong associations between POPs and diabetes were observed in both the higher-BMI (BMI≥25â¯kg/m2) and the lower-BMI (BMI<25â¯kg/m2) groups. POPs showed stronger associations with diabetes in males than in females. The odds ratio (OR) for the highest quartile of ∑POPs was 6.97 for males, nearly two times higher than that for females (ORâ¯=â¯3.58). All these findings suggest that POP exposure may impact the risk of diabetes in Chinese population.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Poluentes Ambientais/efeitos adversos , Adulto , Estudos de Casos e Controles , China , Exposição Ambiental/efeitos adversos , Feminino , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/análise , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Razão de Chances , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/análise , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may be associated with obesogenic effects in offspring. Our study is the first to investigate associations between concentrations of POPs from newborn dried blood spots (DBS) and birth characteristics. METHODS: Concentrations of 10 polychlorinated biphenyl congeners (PCBs), polybrominated diphenyl ether-47 (PBDE-47), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were measured from DBSs collected at birth from 2,065 singleton infants. DBS samples were pooled in groups of five and assayed together to reach limits of detection. Differences in risk of large for gestational age (LGA, defined as >90th percentile of birth weight for sex and gestational age), small for gestational age (SGA, <10th), and preterm birth (gestational age <37 weeks) were estimated using logistic regression per unit (ng/ml) increase in concentration of each chemical, adjusting for individual-level covariates, including maternal age, race/ethnicity, prepregnancy BMI, education, parity, smoking, and infant sex while assuming a gamma distribution and using multiple imputation to account for pools. RESULTS: There were 215 (11.3%) singletons born LGA, 158 (7.5%) born SGA, and 157 (7.6%) born preterm. Higher concentrations of POPs were positively associated with slightly higher risk of LGA and higher birth weight. CONCLUSIONS: Relationships between POPs measured in newborn DBS and birth size were mixed. Pooled analysis methods using DBS could address challenges in limits of detection and costs for population-based research.
Assuntos
Peso ao Nascer/efeitos dos fármacos , Diclorodifenil Dicloroetileno/efeitos adversos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Diclorodifenil Dicloroetileno/sangue , Teste em Amostras de Sangue Seco , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Feminino , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/sangue , Humanos , Recém-Nascido/sangue , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Modelos Logísticos , Masculino , Idade Materna , Bifenilos Policlorados/sangue , Gravidez , Nascimento Prematuro/sangueRESUMO
Thyroid hormones are key hormones involved in growth and development. Changes in their levels can cause embryonic brain developmental damage in the first trimester. Studies have shown that polybrominated diphenyl ethers (PBDEs) have developmental neurotoxicity as environmental pollutants, and exposure during pregnancy can cause irreversible brain damage in offspring, similar to the interference effects of thyroid hormones, but its mechanism has not yet been understood. Since the physiological environment for placental cells is highly hypoxic, in the current study, the human placenta-derived JEG cells were cultured at 1% oxygen, 4% carbon dioxide and 94% nitrogen, to reflect in vivo scenario, and the possible protection of taurine on BDE 209-mediated toxicity in JEG cells was studied. Our data showed that different concentrations of BDE 209 can have profound effects on cell viability and placental deiodinase 3 expression under hypoxic culture condition. Taurine was found to improve BDE 209-induced reductions in cell viability and altered gene and protein expressions of placental deiodinases. The results provide a reference for the establishment of early biomarkers and effective preventive measures.
Assuntos
Éteres Difenil Halogenados/efeitos adversos , Iodeto Peroxidase/metabolismo , Placenta/enzimologia , Taurina/farmacologia , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Placenta/citologia , GravidezRESUMO
PBDEs (stands for polybrominated diphenyl ethers) are extensively utilized flame retardants, and BDE 209 is one of the most widely used congeners. Studies have suggested the general toxic effects of PBDEs on the endocrine system and neural development. Our previous studies found that BDE 209 changed Type 3 iodothyronine deiodinase (Dio 3) expression in human SK-N-AS neuroblastoma cells. The current study was designed to examine the potential protection of taurine on alterations of Dio 3 expression induced by BDE 209 in SK-N-AS cells. Briefly, SK-N-AS cells were pretreated with taurine prior to the BDE 209 treatment, and the cell viability was evaluated by the MTT (methyl-thiazolyl-tetrazolium) assay. The disturbance or restoration in the levels of Dio 3 proteins and mRNA were observed separately by the western blot and qRT-PCR. Our data showed that taurine moderately attenuated BDE 209-mediated the loss of cell viability. Also, taurine moderately prevented the reduction in the Dio 3 protein expression and mRNA expression induced by BDE 209 in the SK-N-AS cells. Our findings indicated that taurine potentially provide the protection on PBDEs-induced toxicity on endocrine and neuro-development.
Assuntos
Iodeto Peroxidase/metabolismo , Taurina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Retardadores de Chama , Éteres Difenil Halogenados/efeitos adversos , Humanos , NeuroblastomaRESUMO
Taurine is an important amino acid for the growth and development of the central nervous system and plays an important role in the development of the nervous system. Many studies have shown that taurine can prevent and repair neurodevelopmental damage, and its mechanism has also become a research hotspot. While most studies focus on nerve cells, less on placental cells that are closely related to early neurodevelopment (developmental neurotoxicity) by modulating fetal circulation level of thyroid hormones. Studies have shown that exposure of placental cells to the common environmental endocrine disruptor BDE 209 during early pregnancy may lead to developmental neurotoxicity due to thyroid hormone interference caused by abnormal expression of deiodinases. Therefore, in this study, the placenta-derived JEG cells cultured at 95% air/5% CO2 was used as a in vitro model, and the potential protection from taurine on BDE 209-mediated cytotoxicity was examined. When BDE 209 was found to cause a decrease in cell viability and disturbance in the gene and protein expressions of placental deiodinase 3, pretreatment of the JEG cells with taurine can moderately reduce the BDE 209-meditated cytotoxicity, and restore gene and protein expressions of placental deiodinase, so that thyroid hormone levels tend to be normal in cell culture medium. Our data suggest that taurine may have some protection on the developmental neurotoxicity caused by BDE 209.
Assuntos
Éteres Difenil Halogenados/efeitos adversos , Iodeto Peroxidase/metabolismo , Placenta/citologia , Taurina/farmacologia , Linhagem Celular , Sobrevivência Celular , Disruptores Endócrinos , Feminino , Humanos , GravidezRESUMO
Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and new flame retardants (NFRs) are known thyroid hormone (TH) disruptors, but their disrupting mechanisms in humans are not completely understood. In this study, we aimed to explore the disrupting mechanisms of the aforementioned chemicals via examining TH-regulated proteins and gene expression in human serum. Adult participants from an e-waste dismantling (exposed group) and a control region (control group) in South China provided blood samples for the research. Some compounds of PCBs, PBDEs, and NFRs showed strong binding affinity to the thyroid-stimulating hormone (TSH), thyroglobulin, thyroxine-binding globulin (TBG), gene expression of TH receptor α (TRα) and ß, and iodothyronine deiodinase I (ID1). The highly exposed individuals had lower levels of TBG, TSH, and expression of TRα, but higher expression of ID1 than those of the control group. The disruption of TH-regulated proteins and gene expression suggested the exertion of different and, at times, even contradictory effects on TH disruption. However, no statistically significant difference was found in the TH levels between the exposed and the control group, implying that the TH disruption induced by these chemicals depends on the combined influence of multiple mechanisms. Gene expression appears to be an effective approach for investigations of TH disruption and the potential health effects.
Assuntos
Resíduo Eletrônico/efeitos adversos , Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Bifenilos Policlorados/sangue , Hormônios Tireóideos/sangue , Adulto , Idoso , China , Feminino , Retardadores de Chama/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Éteres Difenil Halogenados/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/efeitos adversos , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Tireotropina/sangue , Globulina de Ligação a Tiroxina/genética , Globulina de Ligação a Tiroxina/metabolismoRESUMO
BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and their endocrine-disrupting properties have focused growing attention regarding their teratogenic potential. We have recently documented that mothers of children born with hypospadias had been exposed to statistically higher levels of PBDE during pregnancy than mothers of healthy controls. However, it is not known which congeners of PBDE are associated with this putative teratogenic effect. OBJECTIVES: To identify PBDE congeners associated with increased risk for hypospadias. STUDY METHODS: Hair samples from mothers were analyzed and compared between hypospadias cases and healthy controls for eight PBDE congeners using gas chromatography mass spectrometry (GC/MS). Polybrominated diphenyl ether levels were measured in the 0- to 3-cm segment closest to the skull of maternal hair as a proxy for in utero exposure of mothers who lived in the same environment for the duration of their pregnancy. RESULTS: Median maternal hair levels of five PBDE congeners (28, 47, 99, 153, and 154) and of total PBDE (∑PBDE) were significantly higher among mothers of infants with hypospadias (n = 152) than among controls (n = 64). Apparent greater differences in the lower brominated congeners, especially in BDE-47 and BDE-99, may be due to the fact that they had been used in larger amounts, and their persistence properties confer longer exposure. CONCLUSIONS: The majority of the lower brominated PBDE congeners measured in maternal hair exhibited higher PBDE body burden during pregnancy in mothers of infants who were born with hypospadias.
Assuntos
Retardadores de Chama/efeitos adversos , Cabelo/química , Éteres Difenil Halogenados/efeitos adversos , Hipospadia/induzido quimicamente , Hipospadia/epidemiologia , Exposição Materna/efeitos adversos , Canadá , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Éteres Difenil Halogenados/química , Humanos , Incidência , Masculino , Gravidez , Valores de Referência , Medição de Risco , Estatísticas não ParamétricasRESUMO
Mangroves are subject to contamination of polybrominated diphenyl ethers (PBDEs) due to waste and wastewater disposal, and aquaculture effluent (AE) from nearby aquaculture activities. However, the response of mangrove plants to these two stresses and their interaction has seldom been reported. A six-month microcosm study, planted with either Kandelia obovata (Ko) or Avicennia marina (Am), the two most dominant species in South China mangrove swamps, was conducted to investigate the effects of BDE-99, and the interactions of BDE-99 (one of the most abundant PBDE congeners) and AE on growth and physiological responses of these plants. In addition to mixed stressors, both stressors were also applied individually. Results showed that Avicennia was more tolerant to BDE-99 contamination than Kandelia, as reflected by the reduced biomass, but increased superoxide radical (O2-â) release and malondialdehyde (MDA) content in Kandelia. Addition of AE alleviated toxicity of BDE-99 in Kandelia by promoting biomass but lowering oxidative stress and MDA production. The hormesis model also demonstrated that the interaction between BDE-99 and AE on leaf and root MDA and O2-â content in both Kandelia and Avicennia were mostly antagonistic. Activities of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) in both leaf and root of Kandelia were reduced by BDE-99. On the contrary, BDE-99 significantly enhanced the three enzyme activities in Avicennia root at month 3. Addition of AE also significantly enhanced root CAT, POD and SOD activities, and leaf SOD in both plant species to remove excess ROS produced under BDE-99 exposure. These results indicated that the tolerance of mangrove plants to oxidative stresses depended on antioxidative enzymes that were inducible.
Assuntos
Avicennia/fisiologia , Éteres Difenil Halogenados/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Rhizophoraceae/fisiologia , Águas Residuárias/análise , Poluentes Químicos da Água/efeitos adversos , Aquicultura , Avicennia/efeitos dos fármacos , Avicennia/crescimento & desenvolvimento , Rhizophoraceae/efeitos dos fármacos , Rhizophoraceae/crescimento & desenvolvimento , Eliminação de Resíduos LíquidosRESUMO
The effects of sub-lethal doses of polybrominated diphenyl ether (PBDE)-209 in terms of toxicity, oxidative stress, and biomarkers were evaluated in the Sparus aurata fibroblast cell line (SAF-1). Vitality and oxidative stress status were studied after incubation with PBDE for 72 h. Concomitantly, the quantification of proteins related to cell cycle and DNA repair (p53), cell proliferation (extracellular signalâ»regulated kinase 1 (ERK1)), energetic restriction (hypoxia-inducible factor 1 (HIF1)), and redox status (Nuclear factor erythroid 2â»related factor 2 (NRF2)) was also determined after prolonged exposure (7â»15 days) by immunoblotting. Our results demonstrated that rising concentrations of PBDEs exposure-induced oxidative stress, and that this event modulates different cell pathways related to cell cycle, cell signaling, and energetic balance in the long term, indicating the negative impact of sub-lethal dose exposure to cell homeostasis.