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Unknown,Transcriptomics,Genomics,Proteomics

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Toxicogenomic Screen of Replacements for bis(2-ethylhexyl) phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Thomas Nardelli

PROVIDER: E-GEOD-66812 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Toxicogenomic Screen of Replacements for bis(2-ethylhexyl) phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line

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

Transcriptomic effects of mono-(2-ethylhexyl) phthalate and all-trans retinoic acid in the cultured mouse fetal testes

Project description:We report the results of an RNA-seq analysis conducted as part of an experiment investigating the effects of the phthalate, mono-(2-ethylhexyl) phthalate (MEHP), and all-trans retinoic acid (ATRA) on cultured fetal mouse testes. The goal of the study was to determine whether fetal testis toxicity of MEHP is partially driven by disruption of retinoic acid signaling.

2022-02-05 | GSE195969 | GEO

Transcriptomic alterations induced by physiologically relevant level of mono(2-ethylhexyl) phthalate (MEHP) in oocytes and blastocysts

Project description:Mono(2-ethylhexyl) phthalate (MEHP), the main di(2-ethylhexyl) phthalate (DEHP) metabolite, is a known reproductive toxicant. Residual levels of 20 nM MEHP have been found in follicular fluid aspirated from IVF-treated women and DEHP-treated animals. It is not yet clear whether these residual MEHP levels have any effect on the follicle-enclosed oocyte or developing embryo. To clarify this point, bovine oocytes were matured with or without 20 nM MEHP for 22 h. Microarray analysis was performed for both mature oocytes and 7-day blastocysts. A feasibility examination was performed on mature oocytes (n = 200/group) to reveal a possible direct effect on the oocyte proteomic profile. Transcriptome analysis revealed MEHP-induced alterations in the expression of 456 and 290 genes in oocytes and blastocysts, respectively. The differentially expressed genes are known to be involved in various biological pathways, such as transcription process, cytoskeleton regulation and metabolic pathway. Among these, the expression of 9 genes was impaired in both oocytes exposed to MEHP (i.e., direct effect) and blastocysts developed from those oocytes (i.e., carryover effect). In addition, 191 proteins were found to be affected by MEHP in mature oocytes. The study explores, for the first time, the risk associated with exposing oocytes to physiologically relevant MEHP concentrations to the maternal transcripts. Although it was the oocytes that were exposed to MEHP, alterations carried over to the blastocyst stage, following embryonic genome activation, implying that these embryos are of low quality.

2019-05-09 | PXD012092 | Pride

Toxicoproteomics of environmental mixtures in prostate diseases

Project description:These data are from the following 2 experiments: 1. normal prostate stromal cells (BHPRS1) treated with either 0.1 uM mono(2-ethylhexyl) phthalate (MEHP), 3 uM perfluorooctanesulfonic acid (PFOS), the mixture of MEHP+PFOS, or DMSO vehicle (0.06% v/v); n=3 each 2. metastatic prostate epithelial cells (MT10) treated with 50 uM mono(2-ethylhexyl) phthalate (MEHP) or DMSO vehicle (0.06% v/v); n=4 each

2024-05-21 | PXD014428 | Pride

Dose response analysis of monophthalates in the murine embryonic stem cell test

Project description:Three embryotoxic phthalate monoesters, monobutyl phthalate (MBuP), monobenzyl phthalate (MBzP) and mono-(2-ethylhexyl) phthalate (MEHP) and the non-embryotoxic monomethyl phthalate (MMP) were studied for their effects on gene expression at several concentrations that did not induce cytotoxicity. 192 arrays

2014-04-07 | E-GEOD-53969 | biostudies-arrayexpress

DNA Methylation and Transcriptomic Profiles of Early Organogenesis-Stage Mouse Conceptuses after Exposure to Mono-2-Ethylhexyl Phthalate: Effects in the Absence and Presence of Neural Tube Defects

Project description:The goal of this study was to assess changes in gene expression and DNA methylation in response to embryonic exposures to the plasticizer metabolite, mono-2-ethylhexyl phthalate (MEHP). Because we previously observed increased incidence of neural tube defects (NTDs) in exposed embryos, we also stratified our samples by NTD status to examine changes in expression or methylation that may be associated with NTD progression in response to MEHP.

2024-07-31 | GSE180254 | GEO

Dose response analysis of monophthalates in the murine embryonic stem cell test

2014-04-07 | GSE53969 | GEO

Mono(2-ethylhexyl) phthalate induces transcriptomic changes in placental cells based on concentration, fetal sex, and trophoblast cell type

Project description:Phthalates are ubiquitous plasticizer chemicals found in consumer products. Exposure to phthalates during pregnancy has been associated with adverse pregnancy and birth outcomes and differences in placental gene expression in human studies. The objective of this research was to evaluate global changes in placental gene expression via RNA sequencing in two placental cell models following exposure to the phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP). HTR-8/SVneo and primary syncytiotrophoblast cells were exposed to three concentrations (1, 90, 180µM) of MEHP for 24 hours with DMSO (0.1%) as a vehicle control. mRNA and lncRNAs were quantified using paired end RNA sequencing, followed by identification of differentially expressed genes (DEGs) and significant KEGG pathways and enriched transcription factors (TFs). MEHP caused gene expression changes across all concentrations for HTR-8/SVneo and primary syncytiotrophoblast cells. Sex-stratified analysis of primary cells identified different patterns of sensitivity in response to MEHP dose by sex, with male placentas being more responsive to MEHP exposure. Pathway analysis identified 11 KEGG pathways significantly associated with at least one concentration in both cell types. Four ligand-inducible nuclear hormone TFs (PPARG, PPARD, ESR1, AR) were enriched in at least three treatment groups. Overall, we demonstrated that MEHP differentially affects placental gene expression based on concentration, fetal sex, and trophoblast cell type. This study confirms prior studies as enrichment of nuclear hormone TFs were concordant with previously published mechanisms of phthalate disruption, and generates new hypotheses, as we identified many pathways and genes not previously linked to phthalate exposure.

2023-05-01 | GSE217210 | GEO

DNA Methylation Profiles of Early Organogenesis-Stage Mouse Conceptuses after Exposure to Mono-2-Ethylhexyl Phthalate: Effects in the Absence and Presence of Neural Tube Defects

Project description:The goal of this study was to assess whether changes in DNA methylation were observed following MEHP treatment in mouse embryos. Explanted GD8 mouse embryos were exposed to 100 ug/ml mono-2-ethylhexyl phthalate (MEHP) or dimethyl sulfoxide (0.01%; control) in whole embryo culture for 24 h. On GD9 tissues were manually separated using watchmaker's forceps and placed for genomic DNA isolation. At that time, the presennce (positive) or absence (negative) of a neural tube defect in the mouse embryos was noted.

2024-07-31 | GSE180608 | GEO

Transcription profiling of liver in male zebrafish after estradiol exposure and aquatic xenobiotics 17alpha-ethynylestradiol, bis(2-ethylhexyl) phthalate and nonylphenol

Project description:Hepatic gene expression profiling in male Zebrafish in response to estradiol exposure and aquatic xenobiotics 17alpha-ethynylestradiol, Bis(2-ethylhexyl) phthalate and nonylphenol. Male zebrafish (Danio rerio) were purchased from commercial fish farm (Euroaquarium Spa Bologna, Italy). Approximately one hundred and twenty fish were received and divided evenly between three 80 l glass aquaria. Each aquarium was individually heated

2012-12-12 | E-TABM-547 | biostudies-arrayexpress

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