Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.945
Filtrar
1.
J Hazard Mater ; 416: 125862, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492810

RESUMO

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17ß-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway.


Assuntos
Dietilexilftalato , Ovário , Animais , Dietilexilftalato/toxicidade , Estradiol , Feminino , Lactação , Camundongos , Folículo Ovariano
2.
Environ Pollut ; 285: 117362, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34380207

RESUMO

Incubation under controlled laboratory conditions were performed to assess the toxic effects of two plastic derived chemicals, bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP), on the growth, photosynthetic efficiency and photosynthetic activity of the cosmopolitan diatom Chaetoceros decipiens-lorenzianus. Non-axenic diatom cells were exposed to concentrations of BPA and DEHP (separately and in mixture), mimicking concentrations observed in contaminated marine ecosystems, for seven days. Upon short-term exposure (i.e., during the first 48 h), BPA and DEHP induced a slight but significant stimulation of biomass and photosynthetic activity relative to the control, whereas, no significant impact was observed on the photosynthetic efficiency. Nevertheless, this pattern was transient. The stimulation was followed by a return to control conditions for all treatments at the end of incubation. These results showed that the cosmopolitan diatom Chaetoceros was not impacted by representative in situ concentrations of plastic derivatives, thus confirming its ability to thrive in coastal anthropogenic environments.


Assuntos
Diatomáceas , Dietilexilftalato , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/toxicidade , Dietilexilftalato/toxicidade , Ecossistema , Fenóis , Ácidos Ftálicos
3.
Sci Total Environ ; 790: 147990, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380243

RESUMO

The plasticizer di(2-ethylhexyl) phthalate (DEHP) and its hydrolysate mono(2-ethylhexyl) phthalate (MEHP) are major toxicants from plastics, but their association with hormone-dependent cancers has been controversial. We treated the human ovarian cancer cell lines SKOV3 and A2780 with low concentrations of DEHP/MEHP, and found that although no significant effect on cell proliferation was observed, ovarian cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted by submicromolar MEHP but not DEHP. Next, ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) supported enrichment and Kaplan-Meier survival analyses, which identified PI3K/Akt pathway as a pivotal signaling pathway in ovarian cancer. We found that 500 nM MEHP treatment significantly increased PIK3CA expression, which could be reversed by the knockdown of peroxisome proliferator-activated receptor alpha (PPARα). Silencing PIK3CA significantly suppressed the MEHP-induced migration, invasion and EMT. In addition, we validated that MEHP treatment promoted phosphorylation of Akt and degradation of IκB-α, thereby activating NF-κB and enhancing NF-κB nuclear translocation. In nude mice, MEHP exposure significantly promoted the metastasis of ovarian cancer xenografts, which could be suppressed by the treatment of PPARα inhibitor GW6471. Our findings showed that low-dose MEHP promoted ovarian cancer progression through activating PI3K/Akt/NF-κB pathway, in a PPARα-dependent manner.


Assuntos
Dietilexilftalato , Neoplasias Ovarianas , Animais , Linhagem Celular Tumoral , Dietilexilftalato/análogos & derivados , Dietilexilftalato/toxicidade , Feminino , Humanos , Camundongos , Camundongos Nus , NF-kappa B , Neoplasias Ovarianas/induzido quimicamente , PPAR alfa/genética , Fosfatidilinositol 3-Quinases , Ácidos Ftálicos , Proteínas Proto-Oncogênicas c-akt
4.
Environ Pollut ; 286: 117570, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438493

RESUMO

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16-19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3. Animal experiments were performed to confirm and expand findings. Wistar rats were administered DEHP at 0, 5, 50, and 500 mg/kg/d for 8 weeks. The serum and liver levels of TC, TG, HDL-C, and LDL-C, and the liver mRNA and protein levels of SREBP-2, SR-BI, LDLR, and NR1H3 were measured. The results showed that WHR, VAI, and LAP were significantly positively associated with the urinary levels of MECPP and ∑DEHP; the plasma HDL-C level was significantly negatively associated with the levels of MECPP, MCMHP and ∑DEHP; the peripheral blood leukocyte mRNA levels of SREBP-2, NR1H3, and LDLR were significantly positively correlated with the MCMHP level; and the SR-BI mRNA level was significantly positively correlated with the levels of MECPP and MCMHP in adolescents. Moreover, the results of animal experiments showed that DEHP exposure significantly increased the serum levels of TC, HDL-C, and LDL-C in 500 mg/kg/d group, as well as the liver levels of TC and HDL-C, up-regulated SREBP-2 mRNA and protein expression in 50 and 500 mg/kg/d groups. DEHP exposure significantly down-regulated SR-BI and NR1H3 protein expression in the liver of the 500 mg/kg/d group rats. Our findings indicate that DEHP exposure can affect lipid metabolism in adolescents by regulating the expression of lipid metabolism-related genes.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Adolescente , Animais , Dietilexilftalato/toxicidade , Exposição Ambiental , Humanos , Metabolismo dos Lipídeos , Ratos , Ratos Wistar
5.
Artigo em Inglês | MEDLINE | ID: mdl-34444624

RESUMO

Endocrine-disrupting chemicals (EDCs) are found in food and various other substances, including pesticides and plastics. EDCs are easily absorbed into the body and have the ability to mimic or block hormone function. The radioligand binding assay based on the estrogen receptors binding affinity is widely used to detect estrogenic EDCs but is limited to radioactive substances and requires specific conditions. As an alternative, we developed a human cell-based dimerization assay for detecting EDC-mediated ER-alpha (ERα) dimerization using bioluminescence resonance energy transfer (BRET). The resultant novel BRET-based on the ERα dimerization assay was used to identify the binding affinity of 17ß-estradiol (E2), 17α-estradiol, corticosterone, diethylhexyl phthalate, bisphenol A, and 4-nonylphenol with ERα by measuring the corresponding BRET signals. Consequently, the BRET signals from five chemicals except corticosterone showed a dose-dependent sigmoidal curve for ERα, and these chemicals were suggested as positive chemicals for ERα. In contrast, corticosterone, which induced a BRET signal comparable to that of the vehicle control, was suggested as a negative chemical for ERα. Therefore, these results were consistent with the results of the existing binding assay for ERα and suggested that a novel BRET system can provide information about EDCs-mediated dimerization to ERα.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Dimerização , Disruptores Endócrinos/toxicidade , Transferência de Energia , Humanos , Receptores de Estrogênio/metabolismo
6.
Mar Pollut Bull ; 171: 112787, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343753

RESUMO

Few studies have been conducted on aquatic contamination by alternative plasticizers. Phthalates and novel plasticizers were measured in sediments from a highly industrialized lake to assess occurrence, sources, time trends, and ecological risks. Legacy and alternative plasticizers were detected in all sediments. Di(2-ethylhexyl) phthalate (DEHP) was a predominant plasticizer, indicating its popular industrial consumption for the last two decades. Predominant novel plasticizers were changed over time. The highest sedimentary DEHP level was recorded on the global scale. Legacy and alternative plasticizers in creek sediments significantly increased from 2008 to 2016, while those from inshore and offshore regions of the lake significantly decreased in association with a dilution effect caused by the operation of a tidal power plant. Concentration ratios of alternative plasticizers to DEHP increased for the last decade, implying a shift in consumption of plasticizers. Sedimentary DEHP concentrations in creeks exceeded almost all threshold values associated with ecological risks.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Lagos , Plastificantes/análise
7.
Environ Pollut ; 289: 117944, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391046

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHP-induced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 µg/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.


Assuntos
Dietilexilftalato , Animais , Dietilexilftalato/toxicidade , Masculino , Simulação de Acoplamento Molecular , Reprodução , Transcriptoma , Peixe-Zebra/genética
8.
Environ Pollut ; 289: 117939, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426182

RESUMO

Agricultural plastic greenhouse (PG) production can extend the growing season of crops to satisfy domestic consumption in countries such as China. Workers in PGs have potential higher phthalate exposure risks than the general population as phthalate accumulation has been observed in greenhouse soil, air, and crops. To date, biomonitoring tests of phthalates for the working population have not been carried out. To address this shortage, we conducted a pilot study in Shaanxi Province, China, among 35 healthy PG workers by follow-up recording their seasonal dietary habits and work activities and urine sample collection and measurement between 2018 and 2019. The objectives were to uncover the association between phthalate metabolites and the population characteristics, seasonal and diurnal variations and causes, and to estimate exposure risks and contributions of exposure pathways from PG production systems. A total of 13 phthalate metabolite concentrations (Σ13 phthalate metabolites) ranged from 102 to 781 (5th-95th) ng/mL (median: 300 ng/mL). Mono-n-butyl phthalate (MNBP) made up 51.3% of Σ13 phthalate metabolites, followed by the sum of four di-2-ethylhexyl phthalate (DEHP) metabolites (24.2%), mono-2-isobutyl phthalate (MIBP) (13.4%), and mono-ethyl phthalate (MEP) (9.8%). The concentrations of MNBP and MIBP in summer were significantly higher than the levels in winter (p < 0.0001). A total of 62.3% of the PG worker population was shown to have exposure risks, and the proportion was as high as 79.4% in summer. Phthalate exposure of the workers from PG production systems constituted over 20% of the total creatinine-based daily intake, and consuming vegetables and fruit planted in PGs and inhalation in PGs were the two largest exposure pathways. Our findings demonstrate that it is important to protect workers in PGs from phthalate exposure risks, and phasing out the use of plastic materials containing phthalates in PGs is imperative, to guarantee food safety in PGs.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , China , Exposição Ambiental/análise , Humanos , Projetos Piloto , Plásticos
9.
Environ Pollut ; 289: 117978, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426190

RESUMO

Over the past decades, the production and use of hazardous chemicals has increased worldwide, and the incidence of neurological diseases is increasing proportionately. Among these chemicals, Bis(2-ethylhexyl) phthalate (DEHP) is the most common member of the phthalate family used as a plasticizer. The present study assessed the consequences of daily DEHP ingestion and its effects on brain functions related to depressive-like behaviors. Adolescent C57BL/6 male mice ingested different concentrations of DEHP in their diet (2, 20, and 200 mg/kg of diet), and behavioral changes in anxiety, despair, anhedonia, and sociality were investigated. DEHP exposure evoked depressive-like behaviors in a dose-dependent manner for each symptom. The levels of corticosterone and reactive oxygen species/reactive nitrogen species increased in DEHP-exposed groups, suggesting chronic stress-like responses. In the medial prefrontal cortex (mPFC), glutamate and glutamine were decreased, and glutamine synthetase showed lower activity compared to the control group, suggesting imbalanced glutamatergic signaling. Measuring the spontaneous excitatory postsynaptic current of glutamatergic neurons, we found that DEHP ingestion resulted in hypoactive glutamatergic signaling in the mPFC.


Assuntos
Dietilexilftalato , Animais , Dietilexilftalato/toxicidade , Ingestão de Alimentos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Ftálicos , Córtex Pré-Frontal
10.
Environ Toxicol Pharmacol ; 87: 103726, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418532

RESUMO

Epidemiological and experimental studies have shown that di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, can aggravate allergic diseases. DEHP promotes adaptive immune responses, although its effect on the innate immune system remains largely unknown. The present study investigated the effects of DEHP on group 2 innate lymphoid cells (ILC2) that produce Th2 cytokines in response to epithelial cell-derived cytokines, such as interleukin (IL)-33. ILC2 (lineage-negative, CD45.2+, Sca1+, KLRG1+) were isolated from the lungs of C57BL/6 J mice. Co-exposure to DEHP and IL-33 significantly increased IL-5 release from ILC2, whose level was higher than that of the vehicle and IL-33 alone. The effects of DEHP in the presence of IL-33 showed an inverted-U dose-response. The present is the first report showing that DEHP exacerbates allergy through the innate immune system.


Assuntos
Citocinas/imunologia , Dietilexilftalato/toxicidade , Imunidade Inata/efeitos dos fármacos , Interleucina-33/farmacologia , Linfócitos/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hipersensibilidade/imunologia , Interleucina-5/imunologia , Pulmão/citologia , Pulmão/imunologia , Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL
11.
Environ Int ; 156: 106748, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34256300

RESUMO

To effectively incorporate in vitro-in silico-based methods into the regulation of consumer product safety, a quantitative connection between product phthalate concentrations and in vitro bioactivity data must be established for the general population. We developed, evaluated, and demonstrated a modeling framework that integrates exposure and pharmacokinetic models to convert product phthalate concentrations into population-scale risks for phthalates and their substitutes. A probabilistic exposure model was developed to generate the distribution of multi-route exposures based on product phthalate concentrations, chemical properties, and human activities. Pharmacokinetic models were developed to simulate population toxicokinetics using Bayesian analysis via the Markov chain Monte Carlo method. Both exposure and pharmacokinetic models demonstrated good predictive capability when compared with worldwide studies. The distributions of exposures and pharmacokinetics were integrated to predict the population distributions of internal dosimetry. The predicted distributions showed reasonable agreement with the U.S. biomonitoring surveys of urinary metabolites. The "source-to-outcome" local sensitivity analysis revealed that food contact materials had the greatest impact on body burden for di(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), and di(2-propylheptyl) phthalate (DPHP), whereas the body burden of diethyl phthalate (DEP) was most sensitive to the concentration in personal care products. The upper bounds of predicted plasma concentrations showed no overlap with ToxCast in vitro bioactivity values. Compared with the in vitro-to-in vivo extrapolation (IVIVE) approach, the integrated modeling framework has significant advantages in mapping product phthalate concentrations to multi-route risks, and thus is of great significance for regulatory use with a relatively low input requirement. Further integration with new approach methodologies will facilitate these in vitro-in silico-based risk assessments for a broad range of products containing an equally broad range of chemicals.


Assuntos
Dietilexilftalato , Exposição Ambiental , Teorema de Bayes , Monitoramento Biológico , Exposição Ambiental/análise , Humanos , Ácidos Ftálicos
12.
Int J Clin Pract ; 75(10): e14603, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229364

RESUMO

AIMS: It is commonly known that stored blood and blood products are heated before transfusion to prevent hypothermia, which leads to increased di-(2-ethylhexyl) phthalate (DEHP) content leaching into the blood and blood products and thereby causes greater conversion of DEHP to mono (2-ethylhexyl) phthalate (MEHP). However, there has been no study in the literature reporting on the amount of toxic phthalates in blood following the erythrocyte suspension (ES) transfused via warming. In this study, we aimed to investigate the DEHP and MEHP content in blood following the heated ES transfusions administered by DEHP-containing and DEHP-free infusion sets. METHODS: The study included 30 patients that were randomly divided into two groups with 15 patients each: group I underwent ES transfusion via DEHP-containing infusion sets warmed with blood-fluid warmers, and group II underwent ES transfusion via DEHP-free infusion sets warmed with blood-fluid warmers. DEHP and MEHP levels were measured both before and after transfusion. RESULTS: DEHP-free infusion sets led to no increase in the phthalate content, whereas DEHP-containing infusion sets significantly increased the DEHP and MEHP, where the DEHP level increased almost four times (P = .001). CONCLUSION: DEHP-containing products lead to toxicity. Therefore, using DEHP-free medical devices may prevent toxicity in patients undergoing ES transfusion.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Dietilexilftalato/análogos & derivados , Dietilexilftalato/toxicidade , Eritrócitos , Humanos , Ácidos Ftálicos/toxicidade
13.
Sci Total Environ ; 796: 148898, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34280640

RESUMO

Phthalates are chemicals suspected to adversely affect fetal neurodevelopment, but quantifying the fetal exposure is challenging. While prenatal phthalate exposure is commonly quantified in maternal urine, the newborn's meconium may better capture cumulative prenatal exposure. Currently, data on phthalates measured in meconium is sparse. We measured phthalate metabolites in 183 maternal second and 140 third trimester (T2, T3) urine, and in 190 meconium samples collected in an autism enriched-risk pregnancy cohort of 236 mothers. Eleven and eight metabolites were detected in over 90% of urine and meconium samples, respectively. Hydrophilic and hydrophobic metabolites were detected in both biosamples. Most urine phthalate metabolite distributions were similar between T2 and T3. Among metabolites detected in both biosamples, those of di(2-ethylhexyl) phthalate displayed a similar pattern in magnitude across metabolite type. Specifically, T2 creatinine adjusted distribution [median (25%, 75%)] of urine measured mono(2-ethylhexyl-carboxypentyl) (MECPP), mono(2-ethyl-5-hydroxyhexyl) (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were 18.8(11.9, 31.4), 11.8(7.2, 19.1), and 8.9(6.2, 14.2) ng/mg. In meconium these were 16.6(10.9, 23.7), 2.5(1.5, 3.8), and 1.3(0.8, 2.3) ng/g, respectively. Metabolite-to-metabolite correlations were lower in meconium than urine, but patterns were similar. For example, correlation (95% CI) between mono(2-ethylhexyl) phthalate and MECPP was 0.73 (0.66, 0.78), and between MEOHP and MEHHP was 0.96 (0.95, 0.97) in urine as compared to 0.10 (-0.04, 0.24) and 0.31 (0.18, 0.43) respectively in meconium. Correlations between same metabolites measured in urine and meconium were low and differed by metabolite and trimester. Correlation between MEHHP in urine and meconium, for example, was 0.20 (0.008, 0.37) at T3, but 0.05 (-0.12, 0.21) at T2. Our study provides evidence of general population-level prenatal phthalate exposure in a population at high risk for neurodevelopmental disorders and supports the utility of meconium to measure prenatal phthalate exposure but provides little evidence of correlation with exposure measured in prenatal maternal urine.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Estudos de Coortes , Exposição Ambiental , Feminino , Humanos , Recém-Nascido , Exposição Materna , Mecônio , Gravidez , Terceiro Trimestre da Gravidez
14.
Chem Biol Interact ; 348: 109569, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197824

RESUMO

As one of the most important members of Phthalate esters (PAEs), di-(2-ethylhexyl) phthalate (DEHP) is widely used in plastics and known as a male reproductive toxicant. Many studies have shown that soybean isoflavones (SI) can rescue the testicular injury caused by DEHP, but the underlying mechanism is unknown. Because methylation is one of the most important mechanisms for maintaining normal biological functions, we studied whether methylation is involved in testicular injury induced by DEHP and whether SI could counter testicular impairment in peripubertal male Sprague Dawley rats. Compared with the control group, we found that the mRNA levels of testicular Sod2, Gpx1, and Igf-1 significantly decreased in the 900 mg/kg DEHP group (DEHP' group) (P < 0.01); however, in the DEHP + SI group, the mRNA levels of the genes obviously increased compared with the DEHP' group (P < 0.01). Simultaneously, the methylation level changes of testicular Sod2, Gpx1, and Igf-1 were similar to the mRNA levels (P < 0.01). Therefore, DEHP may affect testis and leydig cells via inducing methylation of Sod2, Gpx1, and Igf-1, and SI may rescue the impairments at the methylation level. In summary, SI is supposed to be used in DEHP-induced testicular injury treatment.


Assuntos
Metilação de DNA/efeitos dos fármacos , Dietilexilftalato/toxicidade , Isoflavonas/farmacologia , Soja/química , Testículo/efeitos dos fármacos , Testículo/lesões , Animais , Citoproteção/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Testículo/citologia , Testículo/metabolismo
15.
Elife ; 102021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319233

RESUMO

Exposure to environmental factors during fetal development may lead to epigenomic modifications in fetal germ cells, altering gene expression and promoting diseases in successive generations. In mouse, maternal exposure to di(2-ethylhexyl) phthalate (DEHP) is known to induce defects in spermatogenesis in successive generations, but the mechanism(s) of impaired spermatogenesis are unclear. Here, we showed that maternal DEHP exposure results in DNA hypermethylation of promoters of spermatogenesis-related genes in fetal testicular germ cells in F1 mice, and hypermethylation of Hist1h2ba, Sycp1, and Taf7l, which are crucial for spermatogenesis, persisted from fetal testicular cells to adult spermatogonia, resulting in the downregulation of expression of these genes. Forced methylation of these gene promoters silenced expression of these loci in a reporter assay. These results suggested that maternal DEHP exposure-induced hypermethylation of Hist1h2ba, Sycp1, and Taf7l results in downregulation of these genes in spermatogonia and subsequent defects in spermatogenesis, at least in the F1 generation.


Assuntos
Dietilexilftalato/farmacologia , Exposição Materna/efeitos adversos , Mutação , Ácidos Ftálicos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Animais , Metilação de DNA , Regulação para Baixo , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Ftálicos/química , Plastificantes/efeitos adversos , Gravidez , Espermatogônias/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos
16.
J Hazard Mater ; 417: 126044, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229382

RESUMO

The ubiquitous contamination of di(2-ethylhexyl)phthalate (DEHP) in the environment, biota, and food poses potential ecological and human health risks. DEHP exposure can adversely affect learning and memory, yet the underlying mechanisms remain unclear. In this study, Caenorhabditis elegans was used to investigate the effect of early-life DEHP exposure on age-related long-term associative memory (LTAM) decline, as well as the associations with the cAMP-responsive element-binding protein (CREB) transcription factor and insulin/IGF-1 signaling (IIS). We showed that early-life exposure to DEHP reduced LTAM in wild-type worms at day-0 adulthood. Chronic exposure to DEHP from the L1 stage to day-5 adulthood worsened the age-dependent decline of LTAM. Moreover, the effect of DEHP on age-related LTAM requires CRH-1, a homolog of CREB. Mutations in daf-2, the sole receptor of C. elegans IIS, ameliorated the inhibition of LTAM by DEHP, and the effect depended on daf-16. In addition, daf-2 mutation restored the CRH-1 level in DEHP-exposed worms, and the effect required daf-16. Our study suggests that early-life chronic exposure to DEHP worsens age-related LTAM decline and the effect is associated with CRH-1 and IIS in C. elegans. The evolutionary conservation of IIS and CREB implies possible adverse effects by DEHP across species.


Assuntos
Proteínas de Caenorhabditis elegans , Dietilexilftalato , Adulto , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Dietilexilftalato/toxicidade , Humanos , Insulina , Fator de Crescimento Insulin-Like I , Transtornos da Memória , Fatores de Transcrição
17.
Chemosphere ; 282: 131013, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34090004

RESUMO

We have previously shown that adult male mice exposure to low doses of di(2-ethylhexyl)phthalate (DEHP) alters neural function and behaviour. Whether such exposure also affects the integrity and function of the blood-brain barrier (BBB) remained to be explored. The impact of adult exposure to low doses of DEHP alone or in an environmental phthalate mixture on the BBB integrity and surrounding parenchyma was studied in male mice. Two-month-old C57BL/6J males were orally exposed for 6 weeks to DEHP alone (5, and 50 µg/kg/day) or to DEHP (5 µg/kg/day) in an environmental phthalate mixture. BBB permeability, glial activation and neuroinflammation were investigated in the hypothalamic medial preoptic area (mPOA) and hippocampus involved, respectively on the reproductive and cognitive functions. Exposure to DEHP alone or in a phthalate mixture increased BBB permeability and affected the endothelial accessory tight junction protein zona occludens-1 and caveolae protein Cav-1 in the mPOA and the hippocampal CA1 and CA3 areas. This was associated with an inflammatory profile including astrocyte activation accompanied by enhanced expression of inducible nitric oxide synthase in the mPOA, and a microglial activation in the mPOA and the hippocampal CA1 and CA3 areas. The protein levels of the inflammatory molecule cyclooxygenase-2 were increased in activated microglial cells of the exposed mPOA. None of the major effects induced by DEHP alone or in a mixture was detected in the hippocampal dendate gyrus. The data highlight that environmental exposure to endocrine disruptors such as phthalates, could represent a risk factor for the cerebrovascular function.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Ácidos Ftálicos , Animais , Barreira Hematoencefálica , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Exposição Ambiental , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
Anal Methods ; 13(26): 2926-2935, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34109334

RESUMO

The use of phthalates as plasticizers has been omnipresent, especially in cosmetics and food packaging, despite the proven effects on some organs of humans and animals. Therefore, alterations in living organisms due to phthalate exposure attract the attention of many scientists. Here, we demonstrate a mechanical and chemical investigation of the mentioned effects of di(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) on rat liver by utilizing scanning acoustic microscopy (SAM), Raman spectroscopy (RS) and inductively coupled plasma optical emission spectrometry (ICP-OES) for the first time in the literature, as far as we know. The combined analysis gives insights into the degree of modification in the tissue components and which chemicals lead to these modifications. Our study shows that the acoustic impedance values of tissues of DEHP and DBP delivered mother rats are higher than those of tissues of the control mother rat, while the acoustic impedance values of tissues of offspring rats of DEHP and DBP delivered mother rats do not differ significantly from those of tissues of the control offspring rats of the control mother rat. Besides, RS analysis shows how the incorporation of DEHP into liver tissues changes the configuration and conformation of lipids and fatty acids. ICP-OES results show increased element levels within the tissues of DEHP and DBP delivered rats. Therefore, we can say that phthalates cause modifications within the liver. This study is a preliminary effort to investigate tissues with a mechano-chemical probe.


Assuntos
Dietilexilftalato , Animais , Dietilexilftalato/toxicidade , Fígado , Microscopia Acústica , Ácidos Ftálicos , Ratos , Análise Espectral Raman
19.
Mar Pollut Bull ; 170: 112624, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34146859

RESUMO

Little is known about the combined effect of environmental factors and contaminants on commercially important marine species, and whether this effect differs by sex. In this study, blue mussels were exposed for seven days to both single and combined stressors (i.e., +3 °C elevated temperature and two environmentally relevant concentrations of the plastic softener DEHP, 0.5 and 50 µg/l) in a factorial design. Males were observed to be more sensitive to high temperature, demonstrated by the significant increase in out-of-season spawning gonads and higher gene expression of the antioxidant catalase and the estrogen receptor genes. On the other hand, while the gametogenesis cycle in females was more resilient than in males, DEHP exposure altered the estrogen-related receptor gene expression. We show that the combined stressors DEHP and increased temperature, in environmentally relevant magnitudes, have different consequences in male and female mussels, with the potential to impact the timing and breeding season success in Mytilus spp.


Assuntos
Dietilexilftalato , Mytilus edulis , Mytilus , Poluentes Químicos da Água , Animais , Feminino , Masculino , Plastificantes
20.
Environ Toxicol ; 36(9): 1944-1952, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34165231

RESUMO

Neuroblastoma (NB) is an estrogen-dependent tumor. Mono-2-ethylhexyl phthalate (MEHP) has an estrogen-like effect. However, the effects of MEHP on the progression of NB are not well illustrated. This study was to clarify the effect of Notch pathway on proliferation and cell cycle of SH-SY5Y cell induced by MEHP. The viability of SH-SY5Y and BE2C cells were detected by CCK8; cell cycle and apoptosis were detected by flow cytometry; the protein expression levels of Notch pathway and cell cycle related proteins were detected by Western-blot. Results show that MEHP exposure can promote cell proliferation and altered the cell cycle. MEHP exposure can up-regulate the expression of C-MYC, Cyclin D1, Bcl-2 and affected the Notch pathway. In conclusion, MEHP exposure can promote NB cell proliferation and affect the cell cycle and apoptosis. Notch pathway plays a critical role in accelerating the cell cycle and inhibiting the apoptosis of SH-SY5Y cells caused by MEHP.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Apoptose , Ciclo Celular , Proliferação de Células , Dietilexilftalato/análogos & derivados , Dietilexilftalato/toxicidade , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...