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House Dust-Derived Mixtures of Organophosphate Esters Alter the Phenotype, Function, Transcriptome, and Lipidome of KGN Human Ovarian Granulosa Cells

ABSTRACT: House Dust-Derived Mixtures of Organophosphate Esters Alter the Phenotype, Function, Transcriptome, and Lipidome of KGN Human Ovarian Granulosa Cells

PROVIDER: PRJNA1037087 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26744500.fastq.gz	Fastqsanger.gz
	SRR26744501.fastq.gz	Fastqsanger.gz
	SRR26744502.fastq.gz	Fastqsanger.gz
	SRR26744503.fastq.gz	Fastqsanger.gz
	SRR26744504.fastq.gz	Fastqsanger.gz

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House Dust-Derived Mixtures of Organophosphate Esters Alter the Phenotype, Function, Transcriptome, and Lipidome of KGN Human Ovarian Granulosa Cells

Project description:Background: Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggested that exposure to OPEs may be detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. Objectives: The goal of this study was to elucidate the effects of OPE mixtures representative of those found in Canadian house dust on ovarian granulosa cells. Methods: We used high-content imaging to investigate the effects an environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbation to steroidogenesis was assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using cholesterol assay and global lipidomic profiling. Results: OPE mixtures with distinct structural characteristics altered multiple phenotypic features of KGN cells with different potencies. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Discussion: Exposure to house dust-derived mixtures of OPEs may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPE mixtures and highlights the need to examine the effects of human relevant chemical mixtures.

2024-07-03 | GSE247310 | GEO

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

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

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

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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

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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Impacts of Gestational FireMaster 550 (FM 550) Exposure on the Neonatal Cortex are Sex Specific and Largely Attributable to the Organophosphate Esters

Project description:To investigate the potential underlying neurotoxic effect of developmental exposure to flame retardant mixture, Fire Master 550, or it brominated and organophosphate we performed gene expression profiling in PND1 rat prefrontal cortex.

2022-08-20 | GSE211430 | GEO

Expression profiles of lncRNAs and mRNAs in KGN/shPWRN2 cell lines

Project description:In this study, to identify the target genes of PWRN2, we first constructed lentivirus shRNA vectors to infect the KGN cell lines to gain three KGN/shPWRN2 cell lines with down-regulated PWRN2 expression levels. Then, the expression profiles of mRNAs and lncRNAs in KGN/shPWRN2 cells were determined by microarray. The results revealed thousands of lncRNAs and mRNAs expressed in KGN/shPWRN2. The expression of 176 lncRNAs significantly changed in KGN/shPWRN2 cell lines relative to control NC cell lines. Among these, 118 were up-regulated, whereas 58 were down-regulated. A total of 131 mRNAs significantly changed in expression: 84 were upregulated, and 47 were downregulated (fold change≥2.0, P value<0.05). We further do some bioinformatic analysis for the data. Our results will provide some new information to help us understand the molecular roles of PWRN2.

2018-01-01 | GSE97772 | GEO

Role of YAP/TAZ in KGN human granulosa cell line

Project description:To identify the YAP/TAZ target genes in granulosa cells, DNA microarray experiments were performed in KGN cells where YAP/TAZ were knocked down. The effect of the presence or absence of 8Br-cAMP, an intracellular second messenger of FSH, was also investigated in KGN cells.

2022-11-04 | GSE203080 | GEO

Role of YAP/TAZ in KGN human granulosa cell line [Clariom_S_Human]

2022-11-04 | GSE213916 | GEO

ChIP-seq analysis of G3BP1 in KGN cells

Project description:To investigate whether G3BP1 binds to telomeric DNA, we performed the ChIP-seq analysis of G3BP1 in KGN cells.

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