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Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Developing Rat Brain

ABSTRACT: Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Developing Rat Brain

PROVIDER: PRJNA623626 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11505274.fastq.gz	Fastqsanger.gz
	SRR11505275.fastq.gz	Fastqsanger.gz
	SRR11505276.fastq.gz	Fastqsanger.gz
	SRR11505277.fastq.gz	Fastqsanger.gz
	SRR11505278.fastq.gz	Fastqsanger.gz

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Similar Datasets

Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Developing Rat Brain

Project description:There is a growing need to understand the potential neurotoxicity of organophosphate ester flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial FR mixture Firemaster® 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters (NTs) for the developing brain. We have shown in rats and humans that FRs accumulate in placental tissue, and induce functional changes, including altered neurotransmitter (NT) production. Here we sought to establish if OPFRs (triphenyl phosphate, TPHP, and a mixture of isopropylated triarylphosphate isomers, ITPs) alter placental function and fetal forebrain development, with disruption of tryptophan (Trp) metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1,000, or 2,000 μg/day) or a serotonin (5-HT) agonist (5-MT) for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine (Kyn) metabolic pathways were upregulated. Additionally, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental Trp metabolism.

2020-04-08 | GSE148266 | GEO

Effects of organophosphate flame retardants on Atlantic cod liver cells

Project description:Effects of organophosphate flame retardants on Atlantic cod liver cells

| PRJNA407769 | ENA

Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain.

Project description:There is a growing need to understand the potential neurotoxicity of organophosphate flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial flame retardant mixture Firemaster 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters for the developing brain. We have shown in rats and humans that flame retardants accumulate in placental tissue, and induce functional changes, including altered neurotransmitter production. Here, we sought to establish if OPFRs (triphenyl phosphate and a mixture of isopropylated triarylphosphate isomers) alter placental function and fetal forebrain development, with disruption of tryptophan metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1000, or 2000 μg/day) or a serotonin (5-HT) agonist 5-methoxytryptamine for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine metabolic pathways were upregulated. In addition, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental tryptophan metabolism.

| S-EPMC7357193 | biostudies-literature

Effects of organophosphate flame retardants on Atlantic cod liver cells

Project description:Organophosphorous flame retardants (PFRs) were first reported in the late 1970, and today they account for approximately 20 % of the total use of flame retardants in Europe. PFRs are found ubiquitously in the environment, including remote areas stretching from the Arctic to the Antarctic. Generally, similar levels of PFRs is observed between Arctic and more rural areas. The toxicity of PFRs varies depending on their chemical structure. The World Health Organization have reported LC50 values for mammals and aquatic organisms with high variation from 4.2 to 180 mg/L or 707 to 4700 mg/kg body weight, depending on substance and test species. However, little is known about the toxicity and physiological effects of PFRs to fish, particularly in the Arctic species. Hence, the objective of this study is to determine the effects of PFR exposure on hepatic gene expression patterns in Atlantic cod (Gadus morhua) using liver explants in vitro. Liver explants were exposed to 2-Ethylhexyl diphenyl phosphate (EHDPP), tris(2-chloroisopropyl)phosphate (TCPP), and a mixture of both EHDPP and TCPP for 0, 24 and 48 hours. Samples were analyzed for gene expresson profiling using RNAseq. RNAsequening results suggest that exposure to PFRs differentially expressed genes involved in xenobiotic metabolism. We did not observe any chemical-specific effects on gene expression patterns. However, temporal changes in gene expression were observed. Most of the differentially expressed genes (DE) in 24h exposed samples are related in xenobiotic metabolism, whereas in 48h samples DE genes belong to diverse physiological processes.

2017-12-31 | GSE103954 | GEO

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

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

Transcriptional impact of organophosphate pesticides chlorpyrifos and malathion and their mixture on the juvenile coho salmon olfactory system.

Project description:Exposure to environmental concentrations of organophosphate pesticides in Pacific salmon can cause neurobehavioral injuries leading to loss of survival. However, the molecular mechanisms underlying olfactory impairment remain poorly understood. In the current study, we exposed juvenile salmon to three environmentally-relevant doses of chlorpyrifos (CPF) and malathion (MAL) individually and to three concentrations of binary mixtures of both compounds. Brain acetylcholinesterase (AChE) activity was significantly reduced only in the highest dosage of binary mixture group (47% inhibition). Microarray analysis on RNA from coho olfactory rosettes revealed a number of differentially expressed genes in all exposure groups. Overall, there were little overlapping of affected canonical pathways between CPF groups and MAL groups, suggesting the different biofunctions targeted by these two OP pesticides. Several metabolic and signaling pathways also represented the significant toxicological impact of OP pesticides on olfactory system, such as Aryl Hydrocarbon Receptor Signaling, Xenobiotic Metabolism Signaling, Mitochondrial Dysfunction, Pro-Apoptosis, and Oxidative Stress.

2016-01-25 | GSE47984 | GEO

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

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

2025-01-01 | GSE275797 | GEO

Compost mixture

Project description:Compost mixture Metagenome

| PRJNA903545 | ENA

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

| PRJNA1153022 | ENA

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