Effects of a pyrethroid pesticide deltamethrin on gene expression profiles in mouse neuroblastoma Neuro2a cell
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE176000 | GEO | 2021/06/03
REPOSITORIES: GEO
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Project description:Effects of a pyrethroid pesticide deltamethrin on gene expression profiles in mouse neuroblastoma Neuro2a cell
| PRJNA734568 | ENA
Project description:Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5 mg/kg, a pyrethroid, deltamethrin (DM), at 3 mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational day 17. The transcriptomes of fetal brain (CTL n=18, CPF n= 6, DM n=8) and placenta (CTL n=19, CPF n= 16, DM n=12) were obtained through RNA sequencing, and resulting data was evaluated using weighted gene co-expression networks, differential expression, and pathway analyses. Fourteen brain gene co-expression modules were identified; CPF exposure disrupted the module related to ribosome and oxidative phosphorylation, whereas DM disrupted the modules related to extracellular matrix and calcium signaling. In the placenta, network analyses revealed 12 gene co-expression modules. While CPF exposure disrupted modules related to endocytosis, Notch and Mapk signaling, DM exposure dysregulated modules linked to spliceosome, lysosome and Mapk signaling pathways. Overall, in both tissues, CPF exposure impacted oxidative phosphorylation, while DM was linked to genes involved in spliceosome and cell cycle. The transcription factor Max involved in cell proliferation was overexpressed by both pesticides in both tissues. In summary, gestational exposure to two different classes of pesticide can induce similar pathway-level transcriptome changes in the placenta and the brain; further studies should investigate if these changes are linked to neurobehavioral impairments.
2023-04-06 | GSE228777 | GEO
Project description:We describe initial development of RNA profiling-based assays for detecting pyrethroid pesticides in water. We conducted 48-hour flow-through exposures of Pimephales promelas larvae to lab water and eight nominal concentrations of each of four pyrethroid insecticides: bifenthrin, cypermethrin, esfenvalerate, and (trans) permethrin. Concentration-response curves suggest steep dose responses, and LC50s below most published values. Expression microarray analysis of whole larvae suggests transcriptomic changes can be used to detect these pyrethroids at concentrations well below P. promelas LC50s, and below LC50s of about 70% of aquatic metazoan species. Geneset analysis and intersections between lists of differentially expressed genes failed to identify substantial functional overlaps between these toxicants. Geneset analysis was sensitive to parameter choice, which may reflect the large number of genes analyzed relative to the number of samples, and substantial biological variability relative to effect sizes. Several identified GO terms can be rationalized based on known pyrethroid action, but implications of other highlighted GO terms are unclear.
2018-10-31 | GSE113285 | GEO
Project description:We describe initial development of RNA profiling-based assays for detecting pyrethroid pesticides in water. We conducted 48-hour flow-through exposures of Pimephales promelas adults and larvae to lab water and eight nominal concentrations of each of four pyrethroid insecticides: bifenthrin, cypermethrin, esfenvalerate, and (trans) permethrin. Concentration-response curves suggest steep dose responses, and LC50s below most published values. Expression microarray analysis of dissected brains from adults and whole larvae exposed to cypermethrin and bifenthrin suggests both assay formats can be used to detect these pyrethroids at concentrations well below P. promelas LC50s, and below LC50s of about 70% of aquatic metazoan species. Geneset analysis and intersections between lists of differentially expressed genes failed to identify substantial functional overlaps between these toxicants. Geneset analysis was sensitive to parameter choice, which may reflect the large number of genes analyzed relative to the number of samples, and substantial biological variability relative to effect sizes. Several identified GO terms can be rationalized based on known pyrethroid action, but implications of other highlighted GO terms are unclear.
2018-10-31 | GSE113284 | GEO
Project description:Neurodevelopmental disorders (NDD) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDD, including ADHD, is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin (DPE) in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used a multiomics approach to determine the broadest possible set of pharmacologically relevant changes in mouse brain resulting from DPE. Using a litter-based, split-sample design, we deltamethrin mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. The male offspring were raised to adulthood, euthanized, and whole brain samples pulverized and divided for split-sample transcriptomics, kinomics and multiomics integration. The transcriptome revealed alterations to multiple canonical clock genes. The kinome revealed changes in the activity of multiple kinases involved in synaptic plasticity, and broadly in the AGC kinase family. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascade, synaptic function, and regulation of apoptosis. These results demonstrate that DPE causes a multi-modal biophenotype in the brain relevant to ADHD and identifies new potential avenues for therapeutics.
2023-08-28 | GSE241185 | GEO
Project description:Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Experiment Overall Design: In total 60 samples were analyzed in the present study: vehicle control (n = 12), 1 mg/kg permethrin (n=8), 10 mg/kg permethrin (n = 8), 100 mg/kg permethrin (n = 8), 0.3 mg/kg deltamethrin (n = 8), 1 mg/kg deltamethrin (n = 8), 3 mg/kg deltamethrin (n = 8). Transcriptional profiles for each test subject were obtained independently, without sample pooling. Experiment Overall Design: The publication will include an Appendix Table comparing the variability of RMA values (see Sample VALUE columns) to that of GCOS values (see Sample .CHP files).
2008-06-17 | E-GEOD-7955 | biostudies-arrayexpress
Project description:A variety of contaminants find their way to the marine sediments from different sources, and these contaminants can pose serious risks to the natural marine flora and fauna. For example, pyrethroids, which are a potent pesticide family, are often used in agriculture fields worldwide, and these find their way into the marine environment through run off. Further, pyrethroids are used in farmed Atlantic salmon cages in Chile, Great Britain and Norway. Ammonia is another contaminant that is used in agriculture in form of ammonia-rich fertilizer and can be carried during run-offs to localized rivers and streams. Ammonia is also detectable after emission of effluents from sewage treatment plants and industrial plants like oil refineries and meat processing plants. Contaminants may have short and long term effects on non-target organisms living in the water column or in the marine sediment. Importantly, the sediment ecosystem houses a variety of plants, animals and crustaceans, including the American lobster Homarus americanus. Lobster is the most fished crustacean in New Brunswick and Quebec and its resale and exportation produced over $1.6 billion in 2011. Due to its economic and environmental importance, it is essential to study the effects of contaminants present in its ecosystem. Sediment samples are often used as pollution markers during toxicity testing due to their tendency to accumulate hydrophobic contaminants. To better understand the possible effects of contaminants in sediment, a total gene expression study was developed using the marine amphipod Eohaustorius estuarius. A 10 day spike-in exposure was performed using ammonia and two pyrethroids, namely cypermethrin and deltamethrin. As pyrethroids and ammonia are known to have vastly different mechanisms of action in living organisms, we compared global gene expression patterns following exposure to ammonia against the patterns observed following exposure to pyrethroids. Total gene expression was measured by oligonucleotide microarray. The expression of five genes of interest involved in different biological processes such as metabolism, transcription, translation, immunity and stress, which were found to be differently expressed by microarray, was validated by RT-qPCR. A set of genes was identified that showed differential expression levels in a treatment-dependent manner, thus further highlighting the different mechanisms of action of ammonia and pyrethroids in the marine sediment. This study provides a proof of concept for the use of DNA microarrays with model crustaceans for the study of marine sediment contaminants. This specific study is aimed at evaluating the effect of ammonia and pyrethroid exposure on E.estuarius and to identify possible biomarkers of these exposures.
2014-09-01 | E-GEOD-54214 | biostudies-arrayexpress
Project description:Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Keywords: dose response
2007-10-15 | GSE7955 | GEO
Project description:This work describes the initial development of an omics based assay using 48Hr Pimephales promelas (FHM) larvae for identifying aquatic exposures to four pyrethroids (permethrin, cypermethrin, esfenvalerate and bifenthrin). Gene expression classifiers were developed using the random forest algorithm for each exposure and evaluated first by cross-validation using hold out organisms from the same exposure experiment and then against test sets of each pyrethroid from separate exposure experiments. Bifenthrin exposed organisms generated the highest quality classifier, demonstrating an empirical Area Under the Curve (eAUC) of 0.97 when tested against bifenthrin exposed organisms from other exposure experiments and 0.91 against organisms exposed to any of the pyrethroids. Additionally, the bifenthrin classifier was able to successfully classify organisms from all other pyrethroid exposures at multiple concentrations, suggesting a potential utility for detecting cumulative exposures. Considerable run-to-run variability was observed both in exposure concentrations and molecular responses of exposed fish across exposure experiments. The application of a calibration step in analysis successfully corrected this, resulting in a significantly improved classifier. Classifier evaluation suggested the importance of considering a number of aspects of experimental design when developing an expression based tool for general use in ecological monitoring and risk assessment, such as the inclusion of multiple experimental runs and high replicate numbers.
2016-09-30 | GSE84475 | GEO
Project description:A frightening resurgence of bed bug infestations has occurred over the last 10 years in the US. Current chemical methods have been inadequate for controlling bed bugs due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in US bed bug populations, making it extremely difficult to develop intelligent strategies to control this pest. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. LD50 bioassays determined resistance ratios of ~6000-fold to the insecticide deltamethrin, with contact bioassays confirming cross-resistance to several other labeled formulations. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxyesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.
2011-10-19 | GSE31025 | GEO