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Alteration of the N6-methyladenosine Epitranscriptome Profile in Synthetic Phthalate-treated Human Induced Pluripotent Stem Cell-Derived Endothelial Cells [RNA-seq]

ABSTRACT: Background: This study aims to characterize the N6-methyladensosine epitranscriptomic profile induced by mono(2-ethylhexyl) phthalate (MEHP) exposure using a human-induced pluripotent stem cell-derived endothelial cell model. Methods: A multi-omic approach was employed by performing RNA sequencing in parallel with an m6A-specific microarray to identify mRNAs, lncRNAs, and miRNAs affected by MEHP exposure. Results: An integrative multi-omic analysis identified relevant biological features affected by MEHP, while functional assays provided a phenotypic characterization of these effects. Transcripts regulated by the epitranscriptome were validated with qPCR and Me-RIP. Conclusion: Our findings offer important information regarding the alterations occurring within the m6A epitranscriptome and the gene expression changes which occur in response to treatment with a synthetic phthalate in hiPSC-ECs and may be an important resource for future research.

ORGANISM(S): Homo sapiens

PROVIDER: GSE212641 | GEO | 2022/10/11

REPOSITORIES: GEO

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Alteration of the N6-methyladenosine Epitranscriptome Profile in Synthetic Phthalate-treated Human Induced Pluripotent Stem Cell-Derived Endothelial Cells [array]

Project description:Background: This study aims to characterize the N6-methyladensosine epitranscriptomic profile induced by mono(2-ethylhexyl) phthalate (MEHP) exposure using a human-induced pluripotent stem cell-derived endothelial cell model. Methods: A multi-omic approach was employed by performing RNA sequencing in parallel with an m6A-specific microarray to identify mRNAs, lncRNAs, and miRNAs affected by MEHP exposure. Results: An integrative multi-omic analysis identified relevant biological features affected by MEHP, while functional assays provided a phenotypic characterization of these effects. Transcripts regulated by the epitranscriptome were validated with qPCR and Me-RIP. Conclusion: Our findings offer important information regarding the alterations occurring within the m6A epitranscriptome and the gene expression changes which occur in response to treatment with a synthetic phthalate in hiPSC-ECs and may be an important resource for future research.

2022-10-11 | GSE214419 | 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

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

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

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

2015-08-06 | E-GEOD-66812 | biostudies-arrayexpress

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

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

Mouse retina m6A epitranscriptome

Project description:m6A epitranscriptome of postnatal day 6 mouse retina was sequenced using MeRIP-seq.

2022-12-03 | GSE180814 | GEO

Expression data from HeLa cell treated with Bisphenol S and Mono-ethylhexyl phthalate

Project description:Bisphenol S and mono-ethylhexyl phthalate are widely used in the industry of making plastic, mailing envelopes, tickets, etc. Humans are exposed to these compounds by skin contact, inhalation, and food ingestions. However, the molecular mechanisms of these compounds' adverse effects are still unclear. We address the molecular and cellular mechanisms underlying Bisphenol S and mono-ethylhexyl phthalate effects on HeLa cells. Here microarray analysis was performed to identify distinct classes of up- or down-regulated genes and their connections to the different metabolic pathways.

2020-05-27 | GSE147533 | GEO

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