Mechanistic Evaluation of Reduced Reproduction in Daphnia pulex Exposed to the Insensitive Munition, 1-methyl-3-nitro-1-nitroguanidine (MeNQ)
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ABSTRACT:
PROVIDER: PRJNA692620 | ENA |
REPOSITORIES: ENA
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Project description:The US Department of Defense (DOD) is developing insensitive munitions (IMs) that are resistant to unintended detonation to protect warfighters. To enable evaluation of the material life-cycle for the IM, 1-methyl-3-nitro-1-nitroguanidine (MeNQ), ecotoxicological impacts assessment was required. A previous investigation of MeNQ exposures in Daphnia pulex revealed concentration-responsive decreases in reproduction relative to controls (0 mg/L) across a 174, 346, 709, 1385, and 2286 mg/L exposure range. The present study used those exposures to conduct global transcriptomic expression analyses to establish hypothetical mechanisms underlying inhibited reproduction. Changes in transcript expression tended to increase with increasing MeNQ concentration where hierarchical clustering analysis identified separation among the “low” (174 and 346 mg/L) and “high” (709, 1385, and 2286 mg/L) exposures. The MeNQ exposures significantly decreased transcriptional expression for a vitellogenin precursor and juvenile hormone-inducible protein, each having plausible mechanistic connections to impaired reproductive physiology and reduced offspring production in Daphnia. Further, MeNQ affected chorion peroxidase and high choriolytic enzyme transcriptional expression which are known to influence egg production / maturation processes in arthropods. Additionally, MeNQ exposure caused dose-responsive decreases in transcriptional expression for a diverse set of cuticle proteins which requires closer examination regarding Daphnia embryo development and brood release. Finally, canonical-pathway enrichment analysis identified significant effects on a broad array of energy metabolic processes in D. pulex which require consideration regarding potential shifts in homeostatic equilibrium that can have indirect costs on reproduction. Overall, plausible mechanisms of inhibited D. pulex reproduction have been identified and should be tested in targeted bioassays. see previous row.
2021-06-14 | GSE164957 | GEO
Project description:The US Department of Defense (DOD) is developing insensitive munitions (IMs) that are resistant to unintended detonation to protect warfighters. To enable material life-cycle analysis for the IM, 1-methyl-3-nitro-1-nitroguanidine (MeNQ), ecotoxicological impacts assessment was required. A previous investigation of MeNQ exposures in Daphnia pulex revealed concentration-responsive decreases in reproduction relative to controls (0 mg/L) across a 174, 346, 709, 1385, and 2286 mg/L exposure range. The present study used those exposures to conduct global transcriptomic expression analyses to establish hypothetical mode(s) of action underlying inhibited reproduction. The number of significantly affected transcripts and the magnitude of fold-change differences relative to controls tended to increase with increasing MeNQ concentration where hierarchical clustering analysis identified separation among the "low" (174 and 346 mg/L) and "high" (709, 1385, and 2286 mg/L) exposures. Vitellogenin is critical to Daphnia reproductive processes and MeNQ exposures significantly decreased transcriptional expression for vitellogenin-1 precursor at the lowest exposure level (174 mg/L) with benchmark dose (BMD) levels closely tracking concentrations that caused inhibited reproduction. Additionally, juvenile hormone-inducible protein, chorion peroxidase, and high choriolytic enzyme transcriptional expression were impacted by MeNQ exposure having potential implications for egg production / maturation and overall fecundity. In concert with these effects on specific genes involved in Daphnia reproductive physiology, MeNQ exposures caused significant enrichment of several canonical-pathways responsible for metabolism of cellular energy substrates where BMD levels for transcriptional expression were observed at ≤100 mg/L. These observations imply possible effects on whole-organism energy budgets that may also incur indirect costs on reproduction.
| S-EPMC8295077 | biostudies-literature
Project description:Abstract: The Army is replacing traditional munitions with insensitive munitions (IM) resistant to accidental detonation. Although the parent IM compound nitroguanidine (NQ) is generally not acutely toxic at concentrations >1000 mg/L in aquatic exposures, products formed by intensive UV-degradation resulted in of multiple-order of magnitude increase in toxicity. A methylated congener of NQ, 1-methyl-3-nitroguanidine (MeNQ), is also being assessed for potential use in IM explosive formulations and consequently was here investigated for UV-degradation hazard and bioaccumulation potential. While up to 716 mg/L parent MeNQ caused no significant mortality or effects on growth in in larval P. promelas in 7-d exposures, the same concentration of MeNQ subjected to UV-treatment resulted in 85% mortality. The UV-treatment degraded only 3.3% of the MeNQ (5,800 mg/L stock, UV-treated for 6h at UV 12x > sunlight), indicating that MeNQ degradation products have potentially high potency. The parent MeNQ exposure decreased transcriptional expression of genes within the significantly enriched insulin metabolic pathway suggesting antagonism of bioenergetics pathways which compliments observed, although non-significant, decreases in body weights. Transcriptional expression in the UV-degraded MeNQ exposures resulted in significant enrichment of pathways and functions related to cell cycle, but also erythrocyte function related to O2/CO2 exchange. These functions likely represent the mechanistic source(s) of increased toxicity observed in the UV-degraded MeNQ exposures, which are distinct from previously observed mechanisms underlying increased UV-degraded NQ toxicity in fish.
2020-02-19 | GSE136782 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE25841: Evolutionary Diversification of Duplicated Genes; Experiment A GSE25843: Evolutionary Diversification of Duplicated Genes; Experiments B-I, M-P GSE25845: Evolutionary Diversification of Duplicated Genes; Experiments B-I GSE25850: Evolutionary Diversification of Duplicated Genes; Experiment J GSE25851: Evolutionary Diversification of Duplicated Genes; Experiment L, K GSE25852: Empirical Annotation of the Daphnia pulex genome; Experiment B GSE25855: Empirical Annotation of the Daphnia pulex genome; Experiment A GSE25856: Empirical Annotation of the Daphnia pulex genome; Experiment C Refer to individual Series
2011-02-01 | E-GEOD-25823 | biostudies-arrayexpress
Project description:Abstract — Previous toxicological investigations of the insensitive munition (IM), 3-nitro-1,2,4-triazol-5-one (NTO), demonstrated histopathological and physiological impacts in mammalian testes. The implications of these findings for fish was unknown, therefore we investigated the effects of chronic (21 day) exposures to NTO and an NTO-containing IM formulation called IMX-101 (composed of 2,4-dinitroanisole (DNAN), nitroguanidine (NQ), and NTO) in adult male fathead minnows to assess if impacts on testes were conserved. The NTO exposure caused no significant mortality through the maximum exposure concentration (720 mg/L, measured), however NTO elicited testicular impacts causing significant asynchrony in spermatogenesis and necrosis in secondary spermatocytes at the two highest exposure concentrations (383 mg/L and 720 mg/L) and testicular degeneration at the highest exposure. Microarray-based transcriptomics analysis identified significant enrichment of steroid metabolism pathways and mTORC-signal control of spermatogonia differentiation in NTO exposures each having logical connections to observed asynchronous spermatogenesis. Additionally, NTO impaired transcriptional expression for genes supporting sperm structural and flagellar development including sperm-associated antigen 6 (Spag6). These functional transcriptomic responses are logical contributors underlying impacted reproductive physiology in NTO exposures that ultimately lead to reductions in spermatozoa. In contrast to NTO, the IMX-101 formulation elicited significant mortality at the two highest exposure concentrations of 25.2 and 50.9 mg/L (DNAN nominal + NTO measured + NQ measured). Unlike NTO and NQ, the DNAN component of the IMX-101 formulation underwent significant transformation in the 21d exposure. From previous investigations, neither NTO or NQ caused mortality in fish at >1000 mg/L suggesting that mortality in the present study arose from DNAN / DNAN-attributable transformation products. The 12.6 mg/L IMX-101 exposure caused significant sublethal impacts on testes including sperm necrosis, interstitial fibrosis, and Sertoli-like cell hyperplasia. Transcriptional profiles for IMX-101 indicated significant enrichment on multiple signaling pathways supporting spermatogenesis, mitosis / meiosis, and flagellar structure, all logically connected to observed sperm necrosis. Additionally, pronounced transcriptional increases within the PPARα-RXRα pathway, a known DNAN target, has been hypothesized to correspond to Sertoli cell hyperplasia, presumably as a compensatory response to fulfill the nurse-function of Sertoli cells during spermatogenesis. Overall, the transcriptional results indicated unique molecular responses for NTO and IMX-101. Regarding chemical hazard, NTO impacted testes and impaired spermatogenesis, but at high exposure concentrations (≥ 192 mg/L), whereas the IMX-101 formulation, elicited mortality and impacts on reproductive physiology likely caused by DNAN and its transformation products present at concentrations well below the NTO-component concentration within the IMX-101 mixture formulation. see previous row.
2019-06-21 | GSE127877 | GEO
Project description:Among pollutants released into the environment by human activities, residues of pharmaceutical agents have been identified worldwide, and are an increasing matter of concern because of their potential impact on ecosystems. Because micro-crustaceans, such as daphnids, are sensitive to chemicals and are key organisms in the food chain, they are particularly convenient for studying the effects of these drugs in the aquatic environment. The aim of this study was to analyse differences of protein expression resulting from acute (2 days) and middle-term (7 days) exposure of Daphnia pulex daphnids to the anticancer drug tamoxifen, with the hope to unveil links between the effects of xenobiotics at the organism level and changes at the molecular level. Using a liquid chromatography - mass spectrometry shotgun approach, about 4000 proteins could be identified with a minimum of one unique peptide, providing the largest proteomics dataset of D. pulex published up to now. Considering both time points and tested concentrations, 189 proteins showed a significant fold change, most of the regulated proteins being observed at the highest concentration tested and for the longer exposure time. About one third of significant proteins were positively regulated, whereas two thirds showed decreased levels after tamoxifen treatment. The identity of regulated proteins suggested a decrease in translation, an increase in protein degradation and changes in carbohydrate and lipid metabolism as the major effects of the drug. Besides these impacted processes, which reflect a general stress response of the organism, some other regulated proteins play a role in Daphnia reproduction. These latter results are in accordance with our previous observations of the impact of tamoxifen on D. pulex reproduction, and illustrate the potential of ecotoxicoproteomics to unravel links between xenobiotic effects at the biochemical and at the organismal level.
2014-10-31 | PXD001257 | Pride
Project description:Abstract — Previous toxicological investigations of the insensitive munition (IM), 3-nitro-1,2,4-triazol-5-one (NTO), demonstrated histopathological and physiological impacts in mammalian testes. The implications of these findings for fish was unknown, therefore we investigated the effects of chronic (21 day) exposures to NTO and an NTO-containing IM formulation called IMX-101 (composed of 2,4-dinitroanisole (DNAN), nitroguanidine (NQ), and NTO) in adult male fathead minnows to assess if impacts on testes were conserved. The NTO exposure caused no significant mortality through the maximum exposure concentration (720 mg/L, measured), however NTO elicited testicular impacts causing significant asynchrony in spermatogenesis and necrosis in secondary spermatocytes at the two highest exposure concentrations (383 mg/L and 720 mg/L) and testicular degeneration at the highest exposure. Microarray-based transcriptomics analysis identified significant enrichment of steroid metabolism pathways and mTORC-signal control of spermatogonia differentiation in NTO exposures each having logical connections to observed asynchronous spermatogenesis. Additionally, NTO impaired transcriptional expression for genes supporting sperm structural and flagellar development including sperm-associated antigen 6 (Spag6). These functional transcriptomic responses are logical contributors underlying impacted reproductive physiology in NTO exposures that ultimately lead to reductions in spermatozoa. In contrast to NTO, the IMX-101 formulation elicited significant mortality at the two highest exposure concentrations of 25.2 and 50.9 mg/L (DNAN nominal + NTO measured + NQ measured). Unlike NTO and NQ, the DNAN component of the IMX-101 formulation underwent significant transformation in the 21d exposure. From previous investigations, neither NTO or NQ caused mortality in fish at >1000 mg/L suggesting that mortality in the present study arose from DNAN / DNAN-attributable transformation products. The 12.6 mg/L IMX-101 exposure caused significant sublethal impacts on testes including sperm necrosis, interstitial fibrosis, and Sertoli-like cell hyperplasia. Transcriptional profiles for IMX-101 indicated significant enrichment on multiple signaling pathways supporting spermatogenesis, mitosis / meiosis, and flagellar structure, all logically connected to observed sperm necrosis. Additionally, pronounced transcriptional increases within the PPARα-RXRα pathway, a known DNAN target, has been hypothesized to correspond to Sertoli cell hyperplasia, presumably as a compensatory response to fulfill the nurse-function of Sertoli cells during spermatogenesis. Overall, the transcriptional results indicated unique molecular responses for NTO and IMX-101. Regarding chemical hazard, NTO impacted testes and impaired spermatogenesis, but at high exposure concentrations (≥ 192 mg/L), whereas the IMX-101 formulation, elicited mortality and impacts on reproductive physiology likely caused by DNAN and its transformation products present at concentrations well below the NTO-component concentration within the IMX-101 mixture formulation. see previous row.
2019-07-01 | GSE127878 | GEO
Project description:We report the application of CAGE (Cap Analysis of Gene Expression) on collections of Daphnia pulex individuals representing three major developmental states. This submission comes from a project of Michael Lynch and was funded by a grant from the National Institutes of Health entitled 'Population Genomics of Daphnia pulex' (Project Number: 1R01GM101672-01A1).
2016-09-12 | GSE80141 | GEO
Project description:Investigation of gene expression level changes in Daphnia pulex MFP strain between in the presence or absence of Chaoborus kairomone.
2015-05-13 | GSE63275 | GEO
Project description:Proteogenomics of Gammarus pulex ovaries to define the core-proteome of female reproductive tissues from crustacean amphipods
2015-09-21 | PXD002309 | Pride