Metabolite-driven remodeling of hepatic lipid metabolism by the plasticizer di-isononyl phthalate
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE313258 | GEO | 2026/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:Phthalates are added to polymers in order to increase their flexibility, but leach out of the matrix. Given that these plasticizers are mainly found in water bound to particles, aquatic species are exposed to phthalates. Silurana tropicalis eggs were exposed to high concentrations of three pththalates: dicyclohexyl phthalate (DCHP; 19 mg/L), dimethyl phthalate (DMP; 34 mg/L), and monomethyl phthalate (MMP; 1500 mg/L), along to their respective controls: 0.82% DMSO for DCHP, and water controls for DMP and MMP. The exposure lasted 3 days during embryogenesis. Four pooled of 10 larvae were sampled per treatment and analyzed for gene expression changes using a microarray approach.
2014-07-31 | GSE57675 | GEO
Project description:Di(2-ethylhexyl) phthalate (DEHP) is a phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39–40 days were orally dosed with either vehicle control (corn oil), DEHP (20 μg/kg/day or 200 ug/kg/day), or DiNP (20 μg/kg/day or 100 ug/kg/day) for 10 days. Total ovarian RNA was collected either immediately post-dosing (0 month) or 3 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones both immediatly after treatment as well as 3 months after treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure. RNA sequence analysis was preformed to elucidate the ovarian molecular pathways altered by DEHP or DiNP exposure immediatly after treatment or 3 months after treatment.
2026-01-01 | GSE158473 | GEO
Project description:Human exposure to endocrine disrupting chemicals (EDCs) such as plasticizers contributes to part of metabolic disorders especially in children and adolescents. Immune cells especially macrophages were essential targets of plasticizers, however their roles on plasticizers induced metabolic disorders and the underlying mechanism were poorly elucidated. Here we reported that dicyclohexyl phthalate (DCHP), one substitute for di-2-ethylhexyl phthalate (DEHP), prepubertal exposure decreased adipose tissue mass and increased plasma triglycerides in mice. Mechanistically, adipose tissue macrophages, particularly lipid associated macrophages (LAM), played key role in this systemic metabolic disorder. Phthalates facilitated the formation of LAMs. And LAMs communicated with adipocyte precursors, especially adipose progenitor cells, via APOE-APP interaction, leading to abnormal adipogenesis. Blocking LAMs formation via macrophage-specific PPARγ knockout enabled adaptive adipogenesis, ameliorating DCHP-induced metabolic disorder. Our data highlights the essential role of LAMs in inhibiting adaptive adipogenesis, supplying a scientific basis for EDCs associated metabolic disorder, especially environmental related lipodystrophy.
2025-01-01 | GSE283751 | GEO
Project description:The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility. Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.
2021-05-15 | GSE67397 | GEO
Project description:The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility (Burden et al. 2006 and references therein). Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.
2021-05-15 | GSE67396 | GEO
Project description:The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility. Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.
2021-05-15 | GSE67398 | GEO
Project description:Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARα targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbα pathway that senses endogenous heme level. Keywords: Treatment effect One-color macroarrays, 4 experimental conditions: Control mice (vehicle treated), mice treated with di-(2-ethylhexyl)-phthalate (DEHP) at 30 mg/kg/day (D30), 180 mg/kg/day (D180) or 1100 mg/kg/day (D1100) for 14 days, Biological replicates: 6 controls, 4 D30, 4 D180, 5 D1100, One replicate per array
2010-05-05 | E-GEOD-14629 | biostudies-arrayexpress
Project description:Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARα targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbα pathway that senses endogenous heme level. Keywords: Treatment effect
2009-02-19 | GSE14629 | GEO
Project description:Phthalate plasticizers are being phased out of consumer products because of their endocrine disrupting properties. This has resulted in a need to find safe alternatives that can plasticize polyvinyl chloride (PVC) while being inexpensive and biodegradable. We aim to study the toxicogenomic profile of mono-(2-ethylhexyl) phthalate (MEHP, the active metabolite of bis(2-ethylhexyl) phthalate, DEHP), the commercial plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and three plasticizers in development (1,4 butanediol dibenzoate (BDB), dioctyl succinate (DOS), and dioctyl maleate (DOM)) using the immortalized TM4 Sertoli cell line.
2015-08-06 | GSE66812 | GEO
Project description:Phthalate plasticizers are being phased out of consumer products because of their endocrine disrupting properties. This has resulted in a need to find safe alternatives that can plasticize polyvinyl chloride (PVC) while being inexpensive and biodegradable. We aim to study the toxicogenomic profile of mono-(2-ethylhexyl) phthalate (MEHP, the active metabolite of bis(2-ethylhexyl) phthalate, DEHP), the commercial plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and three plasticizers in development (1,4 butanediol dibenzoate (BDB), dioctyl succinate (DOS), and dioctyl maleate (DOM)) using the immortalized TM4 Sertoli cell line. Each sample contains four biological replicates except for DOS that contains three. The control is 1.0% DMSO as this was the vehicle used to solubilize the test compounds.
2015-08-06 | E-GEOD-66812 | biostudies-arrayexpress