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Gerald T. Ankley - One of the best experts on this subject based on the ideXlab platform.
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first generation annotations for the Fathead Minnow pimephales promelas genome
Environmental Toxicology and Chemistry, 2017Co-Authors: Travis W Saari, Gerald T. Ankley, Anthony L Schroeder, Daniel L VilleneuveAbstract:Ab initio gene prediction and evidence alignment were used to produce the first annotations for the Fathead Minnow (Pimephales promelas) genome. We also describe a genome browser, hosted by the Society of Environmental Toxicology and Chemistry, that provides simplified access to the annotation data in context with the genomic sequence. The present study extends the utility of the Fathead Minnow genome and supports the continued development of this species as a model organism for predictive toxicology. Environ Toxicol Chem 2017;9999:1–7. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
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sequencing and de novo draft assemblies of a Fathead Minnow pimephales promelas reference genome
Environmental Toxicology and Chemistry, 2016Co-Authors: Frank R Burns, Daniel L Villeneuve, Gerald T. Ankley, Amarin L Cogburn, Eric R Waits, Yunjuan Chang, Victor Llaca, Stephane Deschamps, Raymond E Jackson, Robert A HokeAbstract:The present study was undertaken to provide the foundation for development of genome-scale resources for the Fathead Minnow (Pimephales promelas), an important model organism widely used in both aquatic toxicology research and regulatory testing. The authors report on the first sequencing and 2 draft assemblies for the reference genome of this species. Approximately 120× sequence coverage was achieved via Illumina sequencing of a combination of paired-end, mate-pair, and fosmid libraries. Evaluation and comparison of these assemblies demonstrate that they are of sufficient quality to be useful for genome-enabled studies, with 418 of 458 (91%) conserved eukaryotic genes mapping to at least 1 of the assemblies. In addition to its immediate utility, the present work provides a strong foundation on which to build further refinements of a reference genome for the Fathead Minnow. Environ Toxicol Chem 2016;35:212–217. © 2015 SETAC
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sequencing and de novo draft assemblies of a Fathead Minnow pimephales promelas reference genome
Environmental Toxicology and Chemistry, 2016Co-Authors: Frank R Burns, Daniel L Villeneuve, Gerald T. Ankley, Amarin L Cogburn, Eric R Waits, Yunjuan Chang, Victor Llaca, Stephane Deschamps, Raymond E Jackson, Robert A HokeAbstract:The present study was undertaken to provide the foundation for development of genome-scale resources for the Fathead Minnow (Pimephales promelas), an important model organism widely used in both aquatic toxicology research and regulatory testing. The authors report on the first sequencing and 2 draft assemblies for the reference genome of this species. Approximately 120× sequence coverage was achieved via Illumina sequencing of a combination of paired-end, mate-pair, and fosmid libraries. Evaluation and comparison of these assemblies demonstrate that they are of sufficient quality to be useful for genome-enabled studies, with 418 of 458 (91%) conserved eukaryotic genes mapping to at least 1 of the assemblies. In addition to its immediate utility, the present work provides a strong foundation on which to build further refinements of a reference genome for the Fathead Minnow.
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Factors and batches (N) by which Fathead Minnow (PPR) and zebrafish (DRE) microarray samples were organized.
2014Co-Authors: Rong-lin Wang, Daniel L Villeneuve, Gerald T. Ankley, Edward J Perkins, David C. Bencic, Natàlia Garcia-reyero, Adam D. BialesAbstract:Sample sizes were indicated in parenthesis.BPA, bisphenol-A; EE2, 17a-ethynyl estradiol; FAD, fadrozole; FIP, fipronil; FLU, flutamide; GEM, Gemfibrozil; KTC, ketoconazole; PRO, prochloraz; RDX, hexahydro-1,3,5-trinitro-1,3,5-triazine; TRB, 17 -trenbolone; TNT, 2,4,6-trinitrotoluene; TRI, trilostane; VIN, vinclozolin; WLSSD, effluent from Western Lake Superior Sanitary District; RNA Date not determined: 11111, 55555; RNA Person not determined: DDD, YYY.Factors and batches (N) by which Fathead Minnow (PPR) and zebrafish (DRE) microarray samples were organized.
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effects of the insecticide fipronil on reproductive endocrinology in the Fathead Minnow
Environmental Toxicology and Chemistry, 2013Co-Authors: David C. Bencic, Daniel L Villeneuve, Lindsey S Blake, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Adam D. Biales, Dalma Martinovicweigelt, Gerald T. AnkleyAbstract:Gamma-aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic-pituitary-gonadal axis, leading to impaired fish reproduction. The present study used a 21-d Fathead Minnow (Pimephales promelas) reproduction assay to investigate the reproductive toxicity of fipronil (FIP), a broad-spectrum phenylpyrazole insecticide that acts as a noncompetitive blocker of GABA receptor–gated chloride channels. Continuous exposure up to 5 µg FIP/L had no significant effect on most of the endpoints measured, including fecundity, secondary sexual characteristics, plasma steroid and vitellogenin concentrations, ex vivo steroid production, and targeted gene expression in gonads or brain. The gonad mass, gonadosomatic index, and histological stage of the gonad were all significantly different in females exposed to 0.5 µg FIP/L compared with those exposed to 5.0 µg FIP/L; however, there were no other significant effects on these measurements in the controls or any of the other treatments in either males and females. Overall, the results do not support a hypothesized adverse outcome pathway linking FIP antagonism of the GABA receptor(s) to reproductive impairment in fish. Environ Toxicol Chem 2013;32:1828–1834. © 2013 SETAC
Daniel L Villeneuve - One of the best experts on this subject based on the ideXlab platform.
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first generation annotations for the Fathead Minnow pimephales promelas genome
Environmental Toxicology and Chemistry, 2017Co-Authors: Travis W Saari, Gerald T. Ankley, Anthony L Schroeder, Daniel L VilleneuveAbstract:Ab initio gene prediction and evidence alignment were used to produce the first annotations for the Fathead Minnow (Pimephales promelas) genome. We also describe a genome browser, hosted by the Society of Environmental Toxicology and Chemistry, that provides simplified access to the annotation data in context with the genomic sequence. The present study extends the utility of the Fathead Minnow genome and supports the continued development of this species as a model organism for predictive toxicology. Environ Toxicol Chem 2017;9999:1–7. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
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sequencing and de novo draft assemblies of a Fathead Minnow pimephales promelas reference genome
Environmental Toxicology and Chemistry, 2016Co-Authors: Frank R Burns, Daniel L Villeneuve, Gerald T. Ankley, Amarin L Cogburn, Eric R Waits, Yunjuan Chang, Victor Llaca, Stephane Deschamps, Raymond E Jackson, Robert A HokeAbstract:The present study was undertaken to provide the foundation for development of genome-scale resources for the Fathead Minnow (Pimephales promelas), an important model organism widely used in both aquatic toxicology research and regulatory testing. The authors report on the first sequencing and 2 draft assemblies for the reference genome of this species. Approximately 120× sequence coverage was achieved via Illumina sequencing of a combination of paired-end, mate-pair, and fosmid libraries. Evaluation and comparison of these assemblies demonstrate that they are of sufficient quality to be useful for genome-enabled studies, with 418 of 458 (91%) conserved eukaryotic genes mapping to at least 1 of the assemblies. In addition to its immediate utility, the present work provides a strong foundation on which to build further refinements of a reference genome for the Fathead Minnow.
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sequencing and de novo draft assemblies of a Fathead Minnow pimephales promelas reference genome
Environmental Toxicology and Chemistry, 2016Co-Authors: Frank R Burns, Daniel L Villeneuve, Gerald T. Ankley, Amarin L Cogburn, Eric R Waits, Yunjuan Chang, Victor Llaca, Stephane Deschamps, Raymond E Jackson, Robert A HokeAbstract:The present study was undertaken to provide the foundation for development of genome-scale resources for the Fathead Minnow (Pimephales promelas), an important model organism widely used in both aquatic toxicology research and regulatory testing. The authors report on the first sequencing and 2 draft assemblies for the reference genome of this species. Approximately 120× sequence coverage was achieved via Illumina sequencing of a combination of paired-end, mate-pair, and fosmid libraries. Evaluation and comparison of these assemblies demonstrate that they are of sufficient quality to be useful for genome-enabled studies, with 418 of 458 (91%) conserved eukaryotic genes mapping to at least 1 of the assemblies. In addition to its immediate utility, the present work provides a strong foundation on which to build further refinements of a reference genome for the Fathead Minnow. Environ Toxicol Chem 2016;35:212–217. © 2015 SETAC
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environmental gestagens activate Fathead Minnow pimephales promelas nuclear progesterone and androgen receptors in vitro
Environmental Science & Technology, 2014Co-Authors: Laura E Ellestad, Daniel L Villeneuve, Vickie S Wilson, Mary C Cardon, Phillip C Hartig, Ian G Chambers, Jennifer L Farmer, Kyle Stevens, Edward F OrlandoAbstract:Gestagen is a collective term for endogenous and synthetic progesterone receptor (PR) ligands. In teleost fishes, 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 17α,20β,21-trihydroxy-4-pregnen-3-one (20β-S) are the predominant progestogens, whereas in other vertebrates the major progestogen is progesterone (P4). Progestins are components of human contraceptives and hormone replacement pharmaceuticals and, with P4, can enter the environment and alter fish and amphibian reproductive health. In this study, our primary objectives were to clone the Fathead Minnow (FHM) nuclear PR (nPR), to develop an in vitro assay for FHM nPR transactivation, and to screen eight gestagens for their ability to transactivate FHM nPR. We also investigated the ability of these gestagens to transactivate FHM androgen receptor (AR). Fish progestogens activated FHM nPR, with DHP being more potent than 20β-S. The progestin drospirenone and P4 transactivated the FHM nPR, whereas five progestins and P4 transactivated FHM AR, all at enviro...
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Factors and batches (N) by which Fathead Minnow (PPR) and zebrafish (DRE) microarray samples were organized.
2014Co-Authors: Rong-lin Wang, Daniel L Villeneuve, Gerald T. Ankley, Edward J Perkins, David C. Bencic, Natàlia Garcia-reyero, Adam D. BialesAbstract:Sample sizes were indicated in parenthesis.BPA, bisphenol-A; EE2, 17a-ethynyl estradiol; FAD, fadrozole; FIP, fipronil; FLU, flutamide; GEM, Gemfibrozil; KTC, ketoconazole; PRO, prochloraz; RDX, hexahydro-1,3,5-trinitro-1,3,5-triazine; TRB, 17 -trenbolone; TNT, 2,4,6-trinitrotoluene; TRI, trilostane; VIN, vinclozolin; WLSSD, effluent from Western Lake Superior Sanitary District; RNA Date not determined: 11111, 55555; RNA Person not determined: DDD, YYY.Factors and batches (N) by which Fathead Minnow (PPR) and zebrafish (DRE) microarray samples were organized.
Kathleen M Jensen - One of the best experts on this subject based on the ideXlab platform.
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effects of the insecticide fipronil on reproductive endocrinology in the Fathead Minnow
Environmental Toxicology and Chemistry, 2013Co-Authors: David C. Bencic, Daniel L Villeneuve, Lindsey S Blake, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Adam D. Biales, Dalma Martinovicweigelt, Gerald T. AnkleyAbstract:Gamma-aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic-pituitary-gonadal axis, leading to impaired fish reproduction. The present study used a 21-d Fathead Minnow (Pimephales promelas) reproduction assay to investigate the reproductive toxicity of fipronil (FIP), a broad-spectrum phenylpyrazole insecticide that acts as a noncompetitive blocker of GABA receptor–gated chloride channels. Continuous exposure up to 5 µg FIP/L had no significant effect on most of the endpoints measured, including fecundity, secondary sexual characteristics, plasma steroid and vitellogenin concentrations, ex vivo steroid production, and targeted gene expression in gonads or brain. The gonad mass, gonadosomatic index, and histological stage of the gonad were all significantly different in females exposed to 0.5 µg FIP/L compared with those exposed to 5.0 µg FIP/L; however, there were no other significant effects on these measurements in the controls or any of the other treatments in either males and females. Overall, the results do not support a hypothesized adverse outcome pathway linking FIP antagonism of the GABA receptor(s) to reproductive impairment in fish. Environ Toxicol Chem 2013;32:1828–1834. © 2013 SETAC
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effects of a glucocorticoid receptor agonist dexamethasone on Fathead Minnow reproduction growth and development
Environmental Toxicology and Chemistry, 2012Co-Authors: Carlie A Lalone, Daniel L Villeneuve, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Allen W Olmstead, Elizabeth K Medlock, Chad Blanksma, Jenna E CavallinAbstract:Synthetic glucocorticoids are pharmaceutical compounds prescribed in human and veterinary medicine as anti-inflammatory agents and have the potential to contaminate natural watersheds via inputs from wastewater treatment facilities and confined animal-feeding operations. Despite this, few studies have examined the effects of this class of chemicals on aquatic vertebrates. To generate data to assess potential risk to the aquatic environment, we used Fathead Minnow 21-d reproduction and 29-d embryo–larvae assays to determine reproductive toxicity and early-life-stage effects of dexamethasone. Exposure to 500 µg dexamethasone/L in the 21-d test caused reductions in Fathead Minnow fecundity and female plasma estradiol concentrations and increased the occurrence of abnormally hatched fry. Female fish exposed to 500 µg dexamethasone/L also displayed a significant increase in plasma vitellogenin protein levels, possibly because of decreased spawning. A decrease in vitellogenin messenger ribonucleic acid (mRNA) expression in liver tissue from females exposed to the high dexamethasone concentration lends support to this hypothesis. Histological results indicate that a 29-d embryo–larval exposure to 500 µg dexamethasone/L caused a significant increase in deformed gill opercula. Fry exposed to 500 µg dexamethasone/L for 29 d also exhibited a significant reduction in weight and length compared with control fry. Taken together, these results indicate that nonlethal concentrations of a model glucocorticoid receptor agonist can impair fish reproduction, growth, and development. Environ. Toxicol. Chem. 2012;31:611–622. © 2011 SETAC
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effects of a 3β hydroxysteroid dehydrogenase inhibitor trilostane on the Fathead Minnow reproductive axis
Toxicological Sciences, 2008Co-Authors: Daniel L Villeneuve, Lindsey S Blake, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Jeffrey D Brodin, Jenna E Cavallin, Dalma Martinovic, Nathaniel D MuellerAbstract:A number of environmental contaminants and plant flavonoid compounds have been shown to inhibit the activity of 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD). Because 3beta-HSD plays a critical role in steroid hormone synthesis, inhibition of 3beta-HSD represents a potentially important mode of endocrine disruption that may cause reproductive dysfunction in fish or other vertebrates. The objective of this study was to test the hypothesis that exposure to the model 3beta-HSD inhibitor, trilostane, would adversely affect reproductive success of the Fathead Minnow (Pimephales promelas). Results of in vitro experiments with Fathead Minnow ovary tissue demonstrated that trilostane inhibited 17beta-estradiol (E2) production in a concentration- and time-dependent manner, and that the effect was eliminated by providing a substrate (progesterone) that does not require 3beta-HSD activity for conversion to E2. Exposure of fish to trilostane caused a significant reduction in spawning frequency and reduced cumulative egg production over the course of the 21-day test. In females, exposure to 1500 mug trilostane/l reduced plasma vitellogenin concentrations, but did not cause significant histological alterations. In males, average trilostane concentrations as low as 50 mug/l significantly increased testis mass and gonadal somatic index. Trilostane exposure did not influence the abundance of mRNA transcripts coding for 3beta-HSD or other steroidogenesis-regulating proteins in males or females. As a whole, results of this study support the hypothesis that 3beta-HSD inhibition can cause reproductive dysfunction in fish, but did not yield a clear profile of responses at multiple levels of biological organization that could be used to diagnose this mode of action.
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nmr analysis of male Fathead Minnow urinary metabolites a potential approach for studying impacts of chemical exposures
Aquatic Toxicology, 2007Co-Authors: Drew R Ekman, Daniel L Villeneuve, Kathleen M Jensen, Gerald T. Ankley, Dalma Martinovic, Quincy Teng, Timothy W ColletteAbstract:Abstract The potential for profiling metabolites in urine from male Fathead Minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because Fathead Minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D 1H NMR spectra of unlyophilized urine from unexposed male Fathead Minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male Fathead Minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D 1H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of 1H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 μg/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male Fathead Minnow, using urine collected from individual fish.
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what is normal a characterization of the values and variability in reproductive endpoints of the Fathead Minnow pimephales promelas
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2007Co-Authors: Karen H Watanabe, Kathleen M Jensen, Edward F Orlando, Gerald T. AnkleyAbstract:Abstract Jensen et al. [Jensen, K.M., Korte, J.J., Kahl, M.D., Pasha, M.S., Ankley, G.T., 2001. Aspects of basic reproductive biology and endocrinology in the Fathead Minnow ( Pimephales promelas ). Comp. Biochem. Physiol. C 128, 127–141.] investigated aspects of the normal reproductive biology of the Fathead Minnow (FHM, P. promelas ), and subsequent studies have generated a large amount of additional reproductive data for endpoints such as plasma steroid hormone and vitellogenin concentrations, spawn interval, and secondary sex characteristics (i.e., nuptial tubercle score and fat pad weight). These data were analyzed and fitted with statistical distributions to improve understanding of the variability in normal, unexposed, adult male ( n = 154) and female ( n = 186) FHM. Summary statistics for most endpoints were consistent with results from other more limited studies of FHMs. Male fat pad weight, and in both sexes gonad and liver weights were found to be proportional to body weight. Multiple statistical distributions were found to characterize each endpoint with the exception of spawn interval. Based on one of the largest datasets ever compiled for controlled studies, results presented herein provide a robust point of reference for the quantitative assessment of reproductive processes in the Fathead Minnow.
John P Giesy - One of the best experts on this subject based on the ideXlab platform.
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responses of juvenile Fathead Minnow pimephales promelas gut microbiome to a chronic dietary exposure of benzo a pyrene
Environmental Pollution, 2021Co-Authors: Abigail Debofsky, Yuwei Xie, Jonathan K Challis, Niteesh Jain, Markus Brinkmann, Paul D Jones, John P GiesyAbstract:These data are collected from juvenile Fathead Minnows (Pimephales promelas) that were exposed to benzo[a]pyrene (BaP) as well as fish exposed to a solvent control for two weeks via the diet. The samples were sterilely collected from whole Fathead Minnow guts and stored at -80°C until DNA and RNA extraction. The guts were used for 16S rRNA sequencing to analyze the impact of BaP on gut microbial communities. Each fish was analyzed independently (samples were not pooled). The results of this study showed a significant effect of BaP exposure on gut microbial community.
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sensitivity of early life stages of white sturgeon rainbow trout and Fathead Minnow to copper
Ecotoxicology, 2013Co-Authors: David W Vardy, John P Giesy, Markus Hecker, Johanna Oellers, Jon A Doering, Henner HollertAbstract:Populations of white sturgeon (WS; Acipenser transmontanus) are in decline in several parts of the United States and Canada, attributed primarily to poor recruitment caused by degradation of habitats, including pollution with contaminants such as metals. Little is known about sensitivity of WS to contaminants or metals such as copper (Cu). Here, acute (96 h) mortalities of WS early life stages due to exposure to Cu under laboratory conditions are reported. Two standard test species, rainbow trout (Oncorhynchus mykiss) and Fathead Minnow (Pimephales promelas), were exposed in parallel to determine relative sensitivity among species. Swim-up larvae (15 days post-hatch (dph)) and early juveniles (40-45 dph) of WS were more sensitive to Cu (LC50 = 10 and 9-17 lg/L, respectively) than were yolksac larvae (8 dph; LC50 = 22 lg/ L) and the later juvenile life stage (100 dph; LC50 = 54 lg/ L). WS were more sensitive to Cu than rainbow trout and Fathead Minnow at all comparable life stages tested. Yolksac larvae of rainbow trout and Fathead Minnow were 1.8 and 4.6 times, respectively, more tolerant than WS, while swim-up and juvenile life stages of rainbow trout were between 1.4- and 2.4-times more tolerant than WS. When plotted in a species sensitivity distribution with other fishes, the mean acute tox- icity value for early life stage WS was ranked between the 1st and 2nd centile. The WS life stage of greatest Cu sensitivity coincides with the beginning of active feeding and close association with sediment, possibly increasing risk. WS early life stages are sensitive to aqueous copper exposure and site- specific water quality guidelines and criteria should be eval- uated closely to ensure adequate protection.
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toxicity of untreated and ozone treated oil sands process affected water ospw to early life stages of the Fathead Minnow pimephales promelas
Water Research, 2012Co-Authors: Yuhe He, John P Giesy, Sarah Patterson, Nan Wang, Markus Hecker, Jonathan W Martin, Mohamed Gamal Eldin, Steve WisemanAbstract:Due to a policy of no release, oil sands process-affected water (OSPW), produced by the surface-mining oil sands industry in North Eastern Alberta, Canada, is stored on-site in tailings ponds. Currently, ozonation is considered one possible method for remediation of OSPW by reducing the concentrations of dissolved organic compounds, including naphthenic acids (NAs), which are considered the primary toxic constituents. However, further work was needed to evaluate the effectiveness of ozonation in reducing the toxicity of OSPW and to ensure that ozonation does not increase the toxicity of OSPW. This study examined effects of untreated, ozone-treated, and activated charcoal-treated OSPW (OSPW, O3-OSPW, and AC-OSPW) on the early life stage (ELS) of Fathead Minnow (Pimephales promelas). Success of hatching of eggs, spontaneous movement, and incidences of hemorrhage, pericardial edema, and malformation of the spine of embryos were examined. To elucidate the mechanism of toxicity, concentrations of reactive oxygen species (ROS) were measured, and the abundances of transcripts of genes involved in biotransformation of xenobiotics, response to oxidative stress, and apoptosis were quantified by real-time PCR. Compared to the control group, which had an embryo survival rate of 97.9 ± 2.08%, survival was significantly less when exposed to OSPW (43.8 ± 7.12%). Eggs exposed to untreated OSPW exhibited a significantly greater rate of premature hatching, and embryos exhibited greater spontaneous movement. Incidences of hemorrhage (50.0 ± 3.40%), pericardial edema (56.3 ± 7.12%), and malformation of the spine (37.5 ± 5.38%) were significantly greater in embryos exposed to OSPW compared to controls. These effects are typical of exposure to dioxin-like compounds, however, abundance of transcripts of cyp1a was not significantly greater in embryos exposed to OSPW. Significantly greater concentrations of ROS, and greater abundances of transcripts cyp3a, gst, sod, casp9, and apopen compared to controls, indicated that exposure to OSPW caused oxidative stress, which can result in damage to mitochondria and promote activation of caspase enzymes and apoptotic cell death. Removal of dissolved organic constituents by ozone treatment, or by activated charcoal, significantly attenuated all of the adverse effects associated with untreated OSPW. The results suggest that the organic fraction of OSPW can negatively impact the development of Fathead Minnow embryos through oxidative stress and apoptosis, and that ozonation attenuates this developmental toxicity.
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comparison of Fathead Minnow ovary explant and h295r cell based steroidogenesis assays for identifying endocrine active chemicals
Ecotoxicology and Environmental Safety, 2007Co-Authors: Daniel L Villeneuve, Lindsey S Blake, Katie J Greene, Eric Higley, Elizabeth A Makynen, Gerald T. Ankley, John L. Newsted, John P GiesyAbstract:An in vitro steroidogenesis assay using H295R human adenocarcinoma cells has been suggested as a possible alternative to gonad explant assays for use as a Tier I screening assay to detect endocrine active chemicals capable of modulating steroid hormone synthesis. This study is one of the first to investigate the utility of the H295R assay for predicting effects and/or understanding mechanisms of action across species and tissues. Six chemicals, including one selective aromatase inhibitor (fadrozole), four fungicides (fenarimol, ketoconazole, prochloraz, and vinclozolin), and one herbicide (prometon), were tested in both the H295R steroidogenesis assay, and an in vitro steroidogenesis assay using Fathead Minnow ovary explants. All six chemicals caused significant alterations in 17β-estradiol (E2) and/or testosterone (T) production in vitro. Effects of ketoconazole, prochloraz, and prometon were similar in both assays. However, there were differences in the profile of responses for T for fadrozole and fenarimol, and for T and E2 for vinclozolin. In terms of sensitivity, steroid production in the H295R assay was most sensitive for detecting the effects of fadrozole, fenarimol, and prochloraz, but was less sensitive than the Fathead Minnow ovary explant assay to the effects of ketoconazole and vinclozolin. The H295R assay was consistently less variable (among replicates) than the Fathead Minnow ovary explant assay. However, the ovary explant assay was more predictive of in vivo effects of the six chemicals on Fathead Minnows than the H295R system. Further characterization of autoregulatory capacities, interaction of steroid-hormone receptor pathways with steroidogenesis, and metabolic capabilities of each system are needed for either system to provide clear and informative insights regarding a chemical's mechanism of action. Overall, however, results of this study suggest that both the H295R and Fathead Minnow ovary explant assays have utility for identifying endocrine-active chemicals in screening-type applications.
Michael D Kahl - One of the best experts on this subject based on the ideXlab platform.
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effects of the insecticide fipronil on reproductive endocrinology in the Fathead Minnow
Environmental Toxicology and Chemistry, 2013Co-Authors: David C. Bencic, Daniel L Villeneuve, Lindsey S Blake, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Adam D. Biales, Dalma Martinovicweigelt, Gerald T. AnkleyAbstract:Gamma-aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic-pituitary-gonadal axis, leading to impaired fish reproduction. The present study used a 21-d Fathead Minnow (Pimephales promelas) reproduction assay to investigate the reproductive toxicity of fipronil (FIP), a broad-spectrum phenylpyrazole insecticide that acts as a noncompetitive blocker of GABA receptor–gated chloride channels. Continuous exposure up to 5 µg FIP/L had no significant effect on most of the endpoints measured, including fecundity, secondary sexual characteristics, plasma steroid and vitellogenin concentrations, ex vivo steroid production, and targeted gene expression in gonads or brain. The gonad mass, gonadosomatic index, and histological stage of the gonad were all significantly different in females exposed to 0.5 µg FIP/L compared with those exposed to 5.0 µg FIP/L; however, there were no other significant effects on these measurements in the controls or any of the other treatments in either males and females. Overall, the results do not support a hypothesized adverse outcome pathway linking FIP antagonism of the GABA receptor(s) to reproductive impairment in fish. Environ Toxicol Chem 2013;32:1828–1834. © 2013 SETAC
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effects of a glucocorticoid receptor agonist dexamethasone on Fathead Minnow reproduction growth and development
Environmental Toxicology and Chemistry, 2012Co-Authors: Carlie A Lalone, Daniel L Villeneuve, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Allen W Olmstead, Elizabeth K Medlock, Chad Blanksma, Jenna E CavallinAbstract:Synthetic glucocorticoids are pharmaceutical compounds prescribed in human and veterinary medicine as anti-inflammatory agents and have the potential to contaminate natural watersheds via inputs from wastewater treatment facilities and confined animal-feeding operations. Despite this, few studies have examined the effects of this class of chemicals on aquatic vertebrates. To generate data to assess potential risk to the aquatic environment, we used Fathead Minnow 21-d reproduction and 29-d embryo–larvae assays to determine reproductive toxicity and early-life-stage effects of dexamethasone. Exposure to 500 µg dexamethasone/L in the 21-d test caused reductions in Fathead Minnow fecundity and female plasma estradiol concentrations and increased the occurrence of abnormally hatched fry. Female fish exposed to 500 µg dexamethasone/L also displayed a significant increase in plasma vitellogenin protein levels, possibly because of decreased spawning. A decrease in vitellogenin messenger ribonucleic acid (mRNA) expression in liver tissue from females exposed to the high dexamethasone concentration lends support to this hypothesis. Histological results indicate that a 29-d embryo–larval exposure to 500 µg dexamethasone/L caused a significant increase in deformed gill opercula. Fry exposed to 500 µg dexamethasone/L for 29 d also exhibited a significant reduction in weight and length compared with control fry. Taken together, these results indicate that nonlethal concentrations of a model glucocorticoid receptor agonist can impair fish reproduction, growth, and development. Environ. Toxicol. Chem. 2012;31:611–622. © 2011 SETAC
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effects of a 3β hydroxysteroid dehydrogenase inhibitor trilostane on the Fathead Minnow reproductive axis
Toxicological Sciences, 2008Co-Authors: Daniel L Villeneuve, Lindsey S Blake, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Elizabeth J Durhan, Jeffrey D Brodin, Jenna E Cavallin, Dalma Martinovic, Nathaniel D MuellerAbstract:A number of environmental contaminants and plant flavonoid compounds have been shown to inhibit the activity of 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD). Because 3beta-HSD plays a critical role in steroid hormone synthesis, inhibition of 3beta-HSD represents a potentially important mode of endocrine disruption that may cause reproductive dysfunction in fish or other vertebrates. The objective of this study was to test the hypothesis that exposure to the model 3beta-HSD inhibitor, trilostane, would adversely affect reproductive success of the Fathead Minnow (Pimephales promelas). Results of in vitro experiments with Fathead Minnow ovary tissue demonstrated that trilostane inhibited 17beta-estradiol (E2) production in a concentration- and time-dependent manner, and that the effect was eliminated by providing a substrate (progesterone) that does not require 3beta-HSD activity for conversion to E2. Exposure of fish to trilostane caused a significant reduction in spawning frequency and reduced cumulative egg production over the course of the 21-day test. In females, exposure to 1500 mug trilostane/l reduced plasma vitellogenin concentrations, but did not cause significant histological alterations. In males, average trilostane concentrations as low as 50 mug/l significantly increased testis mass and gonadal somatic index. Trilostane exposure did not influence the abundance of mRNA transcripts coding for 3beta-HSD or other steroidogenesis-regulating proteins in males or females. As a whole, results of this study support the hypothesis that 3beta-HSD inhibition can cause reproductive dysfunction in fish, but did not yield a clear profile of responses at multiple levels of biological organization that could be used to diagnose this mode of action.
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ketoconazole in the Fathead Minnow pimephales promelas reproductive toxicity and biological compensation
Environmental Toxicology and Chemistry, 2007Co-Authors: Gerald T. Ankley, Lindsey S Blake, Katie J Greene, Rodney D Johnson, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Daniel L VilleneuveAbstract:: Ketoconazole (KTC) is a model pharmaceutical representing imidazole and triazole pesticides, which inhibit fungal growth through blocking a cytochrome P450 (CYP)-mediated step in ergosterol biosynthesis. Several of these fungicides have been shown to be reversible inhibitors of CYPs in vertebrates (primarily mammals), including CYP isoforms involved in the pathway that converts cholesterol to active sex steroids. In these studies, we assessed the effects of KTC on aspects of steroidogenesis and reproductive function in the Fathead Minnow (Pimephales promelas). Exposure of spawning adults to the fungicide for 21 d significantly decreased egg production at a water concentration as low as 25 microg/L. Despite evidence of reduced ex vivo testosterone production by gonads from KTC-exposed Fathead Minnows, circulating plasma concentrations of sex steroids (testosterone, 17beta-estradiol) were not affected. Exposure to KTC caused an increase in the gonadosomatic index in both sexes and, in males, the fungicide caused a marked proliferation of interstitial (Leydig) cells. In addition, mRNA transcripts for two key steroidogenic enzymes, cytochrome P450 side-chain cleavage (CYP11A) and cytochrome P450 c17alpha hydroxylase/17,20 lyase (CYP17), were elevated by exposure to KTC. Both the changes in transcript levels and proliferation of gonad tissue represent potential adaptive or compensatory responses to impaired steroidogenic capacity. Overall our data indicate that, although KTC does adversely affect steroidogenesis and reproduction in the Fathead Minnow, the fish can compensate to some degree to mitigate effects of the fungicide. This has important implications for the interpretation of data from tests with endocrine-active chemicals.
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effects of the feedlot contaminant 17alpha trenbolone on reproductive endocrinology of the Fathead Minnow
Environmental Science & Technology, 2006Co-Authors: Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Gerald T. AnkleyAbstract:Trenbolone acetate is a growth promoter widely used for beef production in the U.S. Two biologically active metabolites of the acetate, 17β- and 17α-trenbolone, are ligands of vertebrate androgen receptors and comparatively stable in the waste of treated animals. Both have been detected in surface water associated with beef feedlots, suggesting a potential risk to aquatic animals. In previous work we evaluated the effects of β-trenbolone on reproductive endocrinology of the Fathead Minnow (Pimephales promelas) in a 21-day test. The purpose of the present study was to conduct a similar set of experiments with α-trenbolone which, based on binding to mammalian androgen receptors, was expected to be less potent than β-trenbolone. Fecundity of the fish was significantly reduced by α-trenbolone with an EC50 (95% confidence interval) of 0.011 (0.007−0.016) μg/L. In females, α-trenbolone reduced plasma vitellogenin and steroid concentrations and also induced the production of dorsal nuptial tubercles, structures ...
