Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay
Ontology highlight
ABSTRACT:
ORGANISM(S): Pimephales promelas
PROVIDER: GSE207231 | GEO | 2023/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization. Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization.
2024-10-23 | GSE246120 | GEO
Project description:Characterization of the renal transcriptomic response to Yersinia ruckeri/Conseuqences of early life stage thyroid suppression on long-term immune function and the immune response in the fathead minnow (Pimephales promelas)
2020-05-19 | GSE146105 | GEO
Project description:Omics approaches are broadly used to explore endocrine and toxicity-related pathways and functions. Nevertheless, there is still a significant gap in knowledge in terms of understanding the endocrine system and its numerous connections and intricate feedback loops, especially in non-model organisms. The fathead minnow (Pimephales promelas) is a widely used small fish model for aquatic toxicology and regulatory testing, particularly in North America. A draft genome has been published but the amount of available genomic or transcriptomic information is still far behind that of other more broadly studied species, such as the zebrafish. Here, we surveyed the tissue-specific proteome and transcriptome profiles in adult male fathead minnow. To do so, we generated a draft transcriptome using short and long sequencing reads. We also performed RNA sequencing and proteomics analysis on the telencephalon, hypothalamus, liver, and gut of male fish. The main purpose of this analysis was to generate tissue-specific omics data in order to support future aquatic ecotoxicogenomic and endocrine-related studies as well as to improve our understanding of the fathead minnow as an ecological model.
2018-10-15 | PXD010216 | Pride
Project description:Nanoparticles are compounds of emerging concern with largely unknown risks for human and ecological health. It is crucial to evaluate their potential biological impact to prevent unintended adverse effects on human health and the environment. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. We also tested the feasibility of the fathead minnow as an alternative species to elucidate potential adverse effects on humans. Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs for 96h. Microarray analyses were performed on liver and brain. Functional analysis identified potential toxicity pathways and molecular initiating events (MIEs) that were confirmed with functional assays. Data suggested that AgNO3 and PVP-AgNPs had both common and distinct transcriptional effects. The nanoparticles were linked to neurotoxicity and oxidative stress, and identified as a dopamine receptor antagonist. Silver nitrate was also identified as a potential neurotoxicant and was confirmed as adrenergic and cannabinoid receptors antagonist. While silver nitrate and PVP-AgNPs were both potential neurotoxicants, they appeared to act through different MIEs. Fathead minnow is a promising alternative species to elucidate potential adverse effects of relevance to human health. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. FHM were obtained from Aquatic Biosystems (Fort Collins, CO), held in aerated dechlorinated tap water and fed three times daily with Zeigler® AquaTox Feed Gardners, PA, USA). Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs (Luna Innovations, Blackburn, VA) for 96h at 24°C ± 1 with a 90% water change at 48 hours. Microarray analyses were performed on liver and brain.
2013-11-01 | E-GEOD-46520 | biostudies-arrayexpress
Project description:As part of the Great Lakes Restoration Initiative, a series of chemical monitoring and surveillance efforts have detected approximately 550 chemicals in Great Lakes tributaries. Among these, there were 140 chemicals for which no empirical toxicity data were available to support prioritization. The aim of the present study was to generate transcriptomic points of departure (tPODs) for 10 of these compounds and demonstrate how they could be applied in a screening-level prioritization. Organisms representing three different trophic levels of the aquatic food-web (Pimephales promelas – secondary consumer, Daphnia magna-primary consumer, and R. subcapitata-primary producer). were exposed for 24 h to a ½-log dilution series of nominal exposure concentrations typically ranging from 66.7 to 0.021 µM of each chemical. In addition to observations of apical effects such as survival and morphology, whole body transcriptomic responses to each chemical were evaluated with targeted analysis using TempO-seq for P. promelas and D. magna and non-targeted full RNA-seq for R. subcapitata. Benchmark concentrations (BMCs) were calculated for each gene showing a concentration-dependent expression pattern. The tPOD for each chemical-species combination was defined as the 10th percentile of the BMCs. The tPODs ranged from 0.18 to 10.8 µM for P. promelas and 0.32 to 29 µM for D. magna, with the most potent of the chemicals tested being fipronil carboxamide. For R. subcapitata, the tPODs ranged from 0.04 to 1.77 µM, with gabapentin as the most potent chemical tested. Empirically derived tPODs from these data poor chemicals, as well as tPODs from previously tested data rich chemicals, were compared with concentrations detected in the Great Lakes basin. This work demonstrates the potential utility of emerging ecological high-throughput transcriptomics assays to support timely screening and prioritization of data poor environmental contaminants.
2026-06-06 | GSE269503 | GEO
Project description:As part of the Great Lakes Restoration Initiative, a series of chemical monitoring and surveillance efforts have detected approximately 550 chemicals in Great Lakes tributaries. Among these, there were 140 chemicals for which no empirical toxicity data were available to support prioritization. The aim of the present study was to generate transcriptomic points of departure (tPODs) for 10 of these compounds and demonstrate how they could be applied in a screening-level prioritization. Organisms representing three different trophic levels of the aquatic food-web (Pimephales promelas – secondary consumer, Daphnia magna-primary consumer, and R. subcapitata-primary producer). were exposed for 24 h to a ½-log dilution series of nominal exposure concentrations typically ranging from 66.7 to 0.021 µM of each chemical. In addition to observations of apical effects such as survival and morphology, whole body transcriptomic responses to each chemical were evaluated with targeted analysis using TempO-seq for P. promelas and D. magna and non-targeted full RNA-seq for R. subcapitata. Benchmark concentrations (BMCs) were calculated for each gene showing a concentration-dependent expression pattern. The tPOD for each chemical-species combination was defined as the 10th percentile of the BMCs. The tPODs ranged from 0.18 to 10.8 µM for P. promelas and 0.32 to 29 µM for D. magna, with the most potent of the chemicals tested being fipronil carboxamide. For R. subcapitata, the tPODs ranged from 0.04 to 1.77 µM, with gabapentin as the most potent chemical tested. Empirically derived tPODs from these data poor chemicals, as well as tPODs from previously tested data rich chemicals, were compared with concentrations detected in the Great Lakes basin. This work demonstrates the potential utility of emerging ecological high-throughput transcriptomics assays to support timely screening and prioritization of data poor environmental contaminants.
2025-06-06 | GSE268998 | GEO
Project description:As part of the Great Lakes Restoration Initiative, a series of chemical monitoring and surveillance efforts have detected approximately 550 chemicals in Great Lakes tributaries. Among these, there were 140 chemicals for which no empirical toxicity data were available to support prioritization. The aim of the present study was to generate transcriptomic points of departure (tPODs) for 10 of these compounds and demonstrate how they could be applied in a screening-level prioritization. Organisms representing three different trophic levels of the aquatic food-web (Pimephales promelas – secondary consumer, Daphnia magna-primary consumer, and R. subcapitata-primary producer). were exposed for 24 h to a ½-log dilution series of nominal exposure concentrations typically ranging from 66.7 to 0.021 µM of each chemical. In addition to observations of apical effects such as survival and morphology, whole body transcriptomic responses to each chemical were evaluated with targeted analysis using TempO-seq for P. promelas and D. magna and non-targeted full RNA-seq for R. subcapitata. Benchmark concentrations (BMCs) were calculated for each gene showing a concentration-dependent expression pattern. The tPOD for each chemical-species combination was defined as the 10th percentile of the BMCs. The tPODs ranged from 0.18 to 10.8 µM for P. promelas and 0.32 to 29 µM for D. magna, with the most potent of the chemicals tested being fipronil carboxamide. For R. subcapitata, the tPODs ranged from 0.04 to 1.77 µM, with gabapentin as the most potent chemical tested. Empirically derived tPODs from these data poor chemicals, as well as tPODs from previously tested data rich chemicals, were compared with concentrations detected in the Great Lakes basin. This work demonstrates the potential utility of emerging ecological high-throughput transcriptomics assays to support timely screening and prioritization of data poor environmental contaminants.
2025-06-06 | GSE269991 | GEO
Project description:New approach methods (NAMs) can reduce the need for chronic, animal-based toxicity and carcinogenicity bioassays. Here, we apply benchmark dose (BMD) response modeling (BMDExpress 2.3) to transcriptomic data after short-term exposures to three organophosphate pesticides (OPPs) to estimate chronic adverse effect levels in mouse. Specifically, mouse-liver were collected for RNA sequencing after 7-days of exposure, respectively, to several dose-levels of well-known OPPs: fenthion, methidathion and parathion. Transcriptional points-of-departure (TPODs) were compared to chronic, apical points-of-departures (APOD) for each OPP to inform more efficient means of estimating chemical potency and risk. The mouse-liver TPODs for fenthion, methidathion, and parathion were 0.009, 0.093, and 0.046 mg/Kg-day, respectively. These short-term TPODs reflected the relative potencies of the most sensitive, apical effects from the chronic studies with fenthion identified as the most potent OPP. Moreover, the TPODs were 2.3 to 17-fold more sensitive than the chronic APODs for mouse, suggesting utility in using short-term gene response for estimating long-term chemical risk. Further investigation into OPPs’ modes of action identified significant impacts on acetylcholinesterase mRNA abundance (FDR p-value <0.05, |FC|>2) as well as enrichment of canonical pathways (IPA, z-score>|2|) associated with organism death and neurological and immune dysfunctions, which have been known to be affected by OPPs. Despite bioassay-related differences, our results indicate the conservation of key events potentially important to OPPs biological activity and potency across species. While additional research is needed, these results build confidence in using short-term, molecular-based assays for the characterization of toxicity and risk, thereby reducing reliance on chronic, rodent-based studies.
2023-11-13 | GSE240853 | GEO