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Impact of Exposure to an Environmentally Relevant Mixture of Organophosphate Esters on the Adrenal Glands of Sprague Dawley Rats

ABSTRACT: To investigate the gene expression changes observed with exposure to organophosphate esters in the adrenal glands of Sprague Dawley rats.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE275797 | GEO | 2025/01/01

REPOSITORIES: GEO

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Impact of Exposure to an Environmentally Relevant Mixture of Organophosphate Esters on the Adrenal Glands of Sprague Dawley Rats

Project description:Impact of Exposure to an Environmentally Relevant Mixture of Organophosphate Esters on the Adrenal Glands of Sprague Dawley Rats

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An environmentally relevant mixture of organophosphate esters induces cholesterol biosynthesis in THP-1 macrophages

Project description:Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, are environmental toxicants known to disrupt lipid metabolism. Although most studies have focused on individual OPEs, environmental exposures typically involve complex mixtures. Our previous studies demonstrated that a representative OPE mixture from Canadian household dust promotes cholesterol and lipid droplet accumulation in THP-1 macrophages. However, the molecular mechanisms underlying this lipid dysregulation remain unclear. Here, we employed tandem mass tag (TMT)-based quantitative proteomics to investigate how OPE mixtures alter protein expression and lipid regulation in macrophages. THP-1 macrophages were exposed to vehicle or environmentally relevant dilutions (1:100,000 and 1:20,000) of the OPE mixture for 48 hours. Lysates were subjected to TMT labeling and mass spectrometry. Bioinformatic analyses using STRING and Ingenuity Pathway Analysis identified 162 differentially expressed proteins, with unsupervised clustering highlighting cholesterol biosynthesis as a key pathway. Further validation via qPCR and upstream analysis implicated the sterol regulatory element-binding protein 2 (SREBP2) signaling axis in OPE-induced cholesterol biosynthesis. Functional assays revealed that co-treatment with atorvastatin, an HMG-CoA reductase inhibitor, prevented cholesterol accumulation and mitigated lipid droplet formation. These findings provide the first evidence that an environmentally relevant OPE mixture can induce cholesterol biosynthesis in human macrophages.

2026-05-25 | PXD067007 | Pride

Impact of exposure to a mixture of organophosphate esters on the adrenal glands of Sprague Dawley rats.

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Effects of an environmentally relevant mixture of organophosphate esters derived from house dust on endochondral ossification in murine limb bud cultures

Project description:Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers but much remains unknown about their potential toxicity. Previously, we reported that four individual OPEs suppress endochondral ossification in murine limb bud cultures. However, real-life exposure is to complex OPE mixtures. In the present study, we tested the hypothesis that a Canadian household dust-based OPE mixture will affect endochondral ossification in gestation day 13 CD1 mouse embryo limb buds expressing fluorescent markers for the major cell populations involved in the process: COL2A1-ECFP (proliferative chondrocytes), COL10A1-mCherry (hypertrophic chondrocytes), and COL1A1-YFP (osteoblasts). Limbs were cultured for six days in the presence of vehicle or dilutions of the OPE mixture (1/1,000,000, 1/600,000, and 1/300,000). All three OPE mixture dilutions affected cartilage template development and the progression of endochondral ossification, as indicated by the fluorescent markers. The expression of Sox9, the master regulator of chondrogenesis, was unchanged, but the expression of Runx2 and Sp7, which drive chondrocyte hypertrophy and osteoblastogenesis, was dilution-dependently suppressed. RNA sequencing revealed that exposure to the 1/300,000 dilution of the OPE mixture for 24 h downregulated 153 transcripts and upregulated 48 others by at least 1.5-fold. Downregulated transcripts were enriched for those related to the immune system and bone formation. In contrast, upregulated transcripts were enriched for those with stress response functions known to be regulated by ATF4 activation. Thus, exposure to the mixture of OPEs commonly found in house dust may have adverse effects on bone formation.

2020-12-28 | GSE157940 | GEO

A mixture of organophosphate esters sex-specifically impacts monocyte-macrophages in Sprague-Dawley rats.

Project description: Not available

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Effects of an environmentally relevant mixture of organophosphate esters derived from house dust on endochondral ossification in murine limb bud cultures

Project description:Effects of an environmentally relevant mixture of organophosphate esters derived from house dust on endochondral ossification in murine limb bud cultures

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Phenotypic and Functional Outcomes in Macrophages Exposed to an Environmentally Relevant Mixture of Organophosphate Esters <i>in Vitro</i>.

Project description: Not available

| S-EPMC11309092 | biostudies-literature

Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived From House Dust on Endochondral Ossification in Murine Limb Bud Cultures.

Project description: Not available

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Toxicological Mechanisms and Potencies of Organophosphate Esters in KGN Human Ovarian Granulosa Cells as Revealed by High-throughput Transcriptomics

Project description:Despite the growing number of studies reporting potential risks associated with exposure to organophosphate esters (OPEs), their molecular mechanisms of action remain poorly defined. We used the high-throughput TempO-Seq platform to investigate the effects of frequently detected OPEs on the expression of ~3000 environmentally responsive genes in KGN human ovarian granulosa cells. Cells were exposed for 48 h to one of five OPEs (0.1 to 50 μM): tris(methylphenyl) phosphate (TMPP), isopropylated triphenyl phosphate (IPPP), tert-butylphenyl diphenyl phosphate (BPDP), triphenyl phosphate (TPHP), or tris(2-butoxyethyl) phosphate (TBOEP). The sequencing data indicate that four OPEs induced transcriptional changes, whereas TBOEP had no effect within the concentration range tested. Multiple pathway databases were used to predict alterations in biological processes based on differentially expressed genes. At lower concentrations, inhibition of the cholesterol biosynthetic pathway was the predominant effect of OPEs; this was likely a consequence of intracellular cholesterol accumulation. At higher concentrations, BPDP and TPHP had distinct effects, primarily affecting pathways involved in cell cycle progression and other stress responses. Benchmark concentration (BMC) modelling revealed that BPDP had the lowest transcriptomic point of departure. However, in vitro to in vivo extrapolation modeling indicated that TMPP was bioactive at lower concentrations than the other OPEs. We conclude that these new approach methodologies provide information on the mechanism(s) underlying the effects of data-poor compounds and assist in the derivation of protective points of departure for use in chemical read-across and decision-making.

2023-11-07 | GSE241995 | GEO

Ovarian Metabolism of an Environmentally Relevant Phthalate Mixture.

Project description: Not available

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