Toxicogenomic Screen of Replacements for bis(2-ethylhexyl) phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66812 | GEO | 2015/08/06
SECONDARY ACCESSION(S): PRJNA278011
REPOSITORIES: GEO
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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
Project description:Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is a ubiquitous environmental pollutant and may act as an endocrine disruptor. Early life exposures to DEHP may result in anti-androgenic effects, impairing the development of the male reproductive tract. However, data on the long-lasting consequences of such DEHP exposures on adult male reproductive function are still rare and discrepant. Previously, we identified two novel plasticizers, 1,4 butanediol dibenzoate (BDB) and dioctyl succinate (DOS), as potential substitutes for DEHP that did not reproduce classically described endocrine disrupting phenotypes in prepubertal male offspring after maternal exposure. Here, we investigated the consequences of in utero and lactational exposure to BDB and DOS on adult male rat reproductive function in a comparative study with DEHP and a commercially available alternative plasticizer, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH). Timed pregnant Sprague-Dawley rats were gavaged with vehicle or a test chemical (30 or 300 mg/kg/day) from gestation day 8 to postnatal day 21. While DEHP exposure (300 mg/kg/day) significantly increased epididymal weight in the adult, exposure to DINCH, BDB or DOS did not affect reproductive organ weights, steroid levels or sperm quality. Using a toxicogenomic microarray approach, we found that adult testicular gene expression was affected by exposure to the higher dose of DEHP; transcripts such as Nr5a2, Ltf or Runx2 were significantly downregulated, suggesting that DEHP was targeting estrogen signaling. Lesser effects were observed after treatment with either DINCH or BDB. DOS exposure did not produce such effects, confirming its potential as a responsible substitute for DEHP. The data deposited correspond to testicular gene expression in 90 day-old Sprague-Dawley rats after exposure to CORN OIL and 30 or 300 mg/kg/day DEHP, DINCH, BDB or DOS from gestational day 8 to post-natal day 21
2018-02-14 | GSE110553 | 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: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:Since 2008, the consumption of the plasticizer bis (2-ethylhexyl) phthalate (DEHP) in the manufacture of plastic products has been restricted due to several adverse health effects. 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) is increasingly used as a harmless substituent for DEHP. However, the structural similarity to DEHP and first studies demonstrating adverse effects on reproduction and metabolism in rats, suggest that DINCH may act adverse on human health. Still, there is a lack of studies on the biological effects of DINCH, especially in the immune system, which is in constant communication with other tissues and thus crucial for maintaining a functional organism. Here we aimed to investigate the effects of DINCH and its naturally occurring biotransformation product monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to DINCH and MINCH in a concentration range of 10 nM to 10 μM for 4 h, 16 h and 24 h in the presence of LPS.
2022-01-10 | PXD027744 | Pride
Project description:In the present study, a pregnant mouse model exposed to di(2-ethylhexyl) phthalate (DEHP, one of the most common plasticizers) during primordial follicle formation was established. The single-cell transcriptome technology was applied to investigate the roles of melatonin in ovarian cells against DEHP exposure. .
2023-11-30 | GSE246030 | 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:This study provides an evaluation of changes in gene expression associated with diisononyl phthalate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (25 mM and 100 mM) of diisononyl phthalate and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis.
2012-08-28 | GSE40342 | GEO
Project description:Phthalate esters, such as DEHP (bis(2-ethylhexyl) phthalate, are a ubiquitous class of chemicals used as plasticizers in plastic products such as toys and hospital supplies. They are not covalently bound to the polymer matrix and can leach out of products. The goal of this study is to determine whether DEHP adversely affect the zebrafish (Danio rerio) microbiome-gut axis, specifically gut transcriptome. We exposed the fish to 3 ppm DEHP via food for 8 weeks to stimulate chronic exposure. To identify genomic responses of DEHP in gut, we used microarrays followed by differential gene expression analysis. The data were then mapped to changes in cell processes and signaling pathways using Pathway Studio.
2020-01-08 | GSE136285 | GEO