Dataset Information

Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).

ABSTRACT: The organic compound diethylhexyl phthalate (DEHP) represents a high production volume chemical found in cosmetics, personal care products, laundry detergents, and household items. DEHP, along with other phthalates causes endocrine disruption in males. Exposure to endocrine disrupting chemicals has been linked to the development of several adverse health outcomes with apical end points including Non-Alcoholic Fatty Liver Disease (NAFLD). This study examined the adult male zebrafish (Danio rerio) transcriptome after exposure to environmental levels of DEHP and 17?-ethinylestradiol (EE2) using both DNA microarray and RNA-sequencing technologies. Our results show that exposure to DEHP is associated with differentially expressed (DE) transcripts associated with the disruption of metabolic processes in the liver, including perturbation of five biological pathways: 'FOXA2 and FOXA3 transcription factor networks', 'Metabolic pathways', 'metabolism of amino acids and derivatives', 'metabolism of lipids and lipoproteins', and 'fatty acid, triacylglycerol, and ketone body metabolism'. DE transcripts unique to DEHP exposure, not observed with EE2 (i.e. non-estrogenic effects) exhibited a signature related to the regulation of transcription and translation, and ruffle assembly and organization. Collectively our results indicate that exposure to low DEHP levels modulates the expression of liver genes related to fatty acid metabolism and the development of NAFLD.

SUBMITTER: Huff M

PROVIDER: S-EPMC5794889 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).

Huff Matthew M da Silveira Willian A WA Carnevali Oliana O Renaud Ludivine L Hardiman Gary G

Scientific reports 20180201 1

The organic compound diethylhexyl phthalate (DEHP) represents a high production volume chemical found in cosmetics, personal care products, laundry detergents, and household items. DEHP, along with other phthalates causes endocrine disruption in males. Exposure to endocrine disrupting chemicals has been linked to the development of several adverse health outcomes with apical end points including Non-Alcoholic Fatty Liver Disease (NAFLD). This study examined the adult male zebrafish (Danio rerio) ...[more]

PMID: 29391432

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Project description:Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA?+?DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA?+?DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA?+?DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA?+?DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA?+?DEHP group. The OVA?+?DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA?+?DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

Project description:BackgroundWe have previously shown that chronic exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate (DEHP) altered male sexual behavior and induced down-regulation of the androgen receptor (AR) in the neural circuitry controlling this behavior.ObjectivesThe cellular mechanisms induced by chronic exposure of adult male mice to low doses of DEHP alone or in an environmental phthalate mixture were studied.MethodsTwo-month-old C57BL/6J males were exposed orally for 8 wk to DEHP alone (0, 5, or 50μg/kg/d) or to DEHP (50μg/kg/d) in a phthalate mixture. Behavior, dendritic density per 50-μm length, pre-/postsynaptic markers, synapse ultrastructure, and bioenergetic activity were analyzed.ResultsMice exposed to DEHP either alone or in a phthalate mixture differed in mating, emission of ultrasonic vocalizations, and the ability to attract receptive females in urinary preference tests from control mice. Analyses in the medial preoptic area, the key hypothalamic region involved in male sexual behavior, showed lower dendritic spine density and protein levels of glutamate receptors and differences in other postsynaptic components and presynaptic markers between the treated groups. Ultrastructural observation of dendritic synapses by electron microscopy showed comparable morphology between the treated groups. Metabolic analyses highlighted differences in hypothalamic metabolites of males exposed to DEHP alone or in a phthalate mixture compared to control mice. These differences included lower tryptophan and higher NAD+ levels, respectively, a precursor and end product of the kynurenine pathway of tryptophan metabolism. The protein amounts of the xenobiotic aryl hydrocarbon receptor, one of the targets of this metabolic pathway and known negative regulator of the AR, were higher in the medial preoptic area of exposed male mice.DiscussionDifferences in behavior of male mice exposed to environmental doses of phthalates were associated with differences in neural structure and metabolism, with possibly a key role of the kynurenine pathway of tryptophan metabolism in the effects mediated by these substances. https://doi.org/10.1289/EHP11514.

Project description:IntroductionDEHP is an endocrine disruptor widely used in the production of malleable plastics. DEHP exposure was associated with altered hypothalamic-pituitary-thyroid (HPT) axis function. Although previous studies reported deleterious effects of DEHP exposure during the intrauterine period, few studies have evaluated the direct effects triggered by this endocrine disruptor on the offspring animals' thyroid function. This study aimed to investigate the impact of intrauterine exposure to DEHP on the HPT axis function programming of the offspring animals during adulthood.MethodsPregnant Wistar rats were orally treated with corn oil or corn oil supplemented with DEHP (0.48 or 4.8 mg/kg/day) throughout the gestational period. The offspring rats were euthanized on the 90th postnatal day. Hypothalamus, pituitary, thyroid, and liver were collected to analyze gene expression and protein content through qPCR and Western Blot. Blood was collected to determine TSH and thyroid hormone levels through fluorometric or chemiluminescence immunoassays.ResultsIn the adult F1 female rats, the highest dose of DEHP decreased TSH serum levels. In the thyroid, DEHP reduced the gene expression and/or protein content of NIS, TSHR, TG, TPO, MCT8, NKX2.1, PAX8, and FOXE1. These data are consistent with the reduction in T4 serum levels of the F1 DEHP-exposed female rats. In the liver, DEHP exposure increased the mRNA expression of Dio1 and Ttr, while the highest dose of DEHP reduced the mRNA expression of Ugt1a1 and Ugt1a6. Conversely, in the F1 male adult rats, TSHB expression and TSH serum levels were increased in DEHP-exposed animals. In the thyroid, except for the reduced protein content of TSHR, none of the evaluated genes/proteins were altered by DEHP. TH serum levels were not changed in the DEHP-exposed F1 male rats compared to the control group. Additionally, there were no significant alterations in the expression of hepatic enzymes in these animals.Discussion/conclusionsOur results demonstrated, for the first time, that intrauterine exposure to DEHP disrupts the HPT axis function in male and female offspring rats and strongly suggest that DEHP exposure increases the susceptibility of the offspring animals to develop thyroid dysfunctions during adulthood.

Dataset Information

Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).

Publications

Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).

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