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Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are ubiquitous contaminants that can be formed through oxidation of parent PAHs. Our previous studies found 2-hydroxychrysene (2-OHCHR) to be significantly more toxic to Japanese medaka embryos than 6-hydroxychrysene (6-OHCHR), an example of regioselective toxicity. We have also previously identified a sensitive developmental window to 2-OHCHR toxicity that closely coincided with liver development, leading us to hypothesize that differences in metabolism may play a role in the regioselective toxicity. To test this hypothesis, Japanese medaka embryos were treated with each isomer for 24 h during liver development (52–76 hpf). Although 6-OHCHR was absorbed 97.2 ± 0.18% faster than 2-OHCHR, it was eliminated 57.7 ± 0.36% faster as a glucuronide conjugate. Pretreatment with cytochrome P450 inhibitor, ketoconazole, reduced anemia by 96.8 ± 3.19% and mortality by 95.2 ± 4.76% in 2-OHCHR treatments. Formation of chrysene-1,2-diol (1,2-CAT) was also reduced by 64.4 ± 2.14% by ketoconazole pretreatment. While pretreatment with UDP-glucuronosyltransferase inhibitor, nilotinib, reduced glucuronidation of 2-OHCHR by 52.4 ± 2.55% and of 6-OHCHR by 63.7 ± 3.19%, it did not alter toxicity for either compound. These results indicate that CYP-mediated activation, potentially to 1,2-CAT, may explain the isomeric differences in developmental toxicity of 2-OHCHR.

Previous studies have shown that altered expression of a family of small noncoding RNAs (microRNAs, or miRs) regulates the expression of downstream mRNAs and is associated with diseases and developmental disorders. miR133b is highly expressed in mammalian cardiac and skeletal muscle, and aberrant expression is associated with cardiac disorders and electrophysiological changes in cardiomyocytes. Similarly, cardiac dysfunction has been observed in early life-stage mahi-mahi (Coryphaena hippurus) exposed to crude oil, a phenotype that has been associated with an upregulation of miR133b as well as subsequent downregulation of a delayed rectifier potassium channel (IKr) and calcium signaling genes that are important for proper heart development during embryogenesis. To examine the potential role of miR133b in oil-induced early life-stage cardiotoxicity in fish, cleavage-stage zebrafish (Danio rerio) embryos were either (1) microinjected with ∼3 nL of negative control miR (75 μM) or miR133b (75 μM) or (2) exposed to a treatment solution containing 5 μM benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, as a positive control. At 72 h post fertilization (hpf), miR133b-injected fish exhibited BaP-like cardiovascular malformations, including a significantly increased pericardial area relative to negative control miR-injected embryos, as well as a significantly reduced eye area. qPCR revealed that miR133b microinjection decreased the abundance of cardiac-specific IKr kcnh6 at 5 hpf, which may contribute to action potential elongation in oil-exposed cardiomyocytes. Additionally, ryanodine receptor 2, a crucial calcium receptor in the sarcoplasmic reticulum, was also downregulated by miR133b. These results indicate that an oil-induced increase in miR133b may contribute to cardiac abnormalities in oil-exposed fish by targeting cardiac-specific genes essential for proper heart development.

The global sequencing of microRNA (miRNA; miR) and integration to downstream mRNA expression profiles in early life stages (ELS) of fish following exposure to crude oil determined consistently dysregulated miRNAs regardless of the oil source or fish species. The overlay of differentially expressed miRNAs and mRNAs into in silico software determined that the key roles of these miRNAs were predicted to be involved in cardiovascular, neurological and visually-mediated pathways. Of these, altered expression of miRNAs, miR-203a and miR-34b were predicted to be primary targets of crude oil. To better characterize the effect of these miRNAs to downstream transcript changes, zebrafish embryos were microinjected at 1 h post fertilization (hpf) with either a miR-203a inhibitor or miR-34b. Since both miRs have been shown to be associated with aryl hydrocarbon receptor (AhR) function, benzo(a)pyrene (BaP), a potent AhR agonist, was used as a potential positive control. Transcriptomic profiling was conducted on injected and exposed larvae at 7 and 72 hpf, and eye morphology assessed following exposure at 72 hpf. The top predicted physiological system disease and functions between differentially expressed genes (DEGs) shared with miR-203a inhibitor-injected and miR-34b-injected embryos were involved in brain formation, and the development of the central nervous system and neurons. When DEGs of miR-203a inhibitor-injected embryos were compared with BaP-exposed DEGs, alterations in nervous system development and function, and abnormal morphology of the neurosensory retina, eye and nervous tissue were predicted, consistent with both AhR and non-AhR pathways. When assessed morphologically, the eye area of miR-203a inhibitor and miR-34b-injected and BaP-exposed embryos were significantly reduced. These results suggest that miR-203a inhibition and miR-34b overexpression contribute to neurological, cardiovascular and eye toxicity responses that are caused by oil and PAH exposure in ELS fish, and are likely mediated through both AhR and non-AhR pathways.

Bifenthrin (BF) is a widely used pyrethroid that has been frequently detected in surface waters. Previous studies indicated that BF had antiestrogenic activity in zebrafish embryos but estrogenic activity in posthatch fish. To determine whether age-related differences in metabolism contribute to the endocrine effects in developing fish, embryos from zebrafish and Japanese medaka were exposed to BF before and after liver development. Since the commercial mixture of BF is an isomer-enriched product containing two enantiomers (1R-cis-BF and 1S-cis-BF), enantioselective metabolism was also evaluated. The estrogenic metabolite, 4-hydroxybifenthrin (4-OH-BF) was identified in zebrafish embryos, and formation was higher in animals after liver development (>48 hpf). Treatments with β-glucuronidase indicated that 4-OH-BF underwent conjugation in embryos. Formation was reduced by cotreatment of the cytochrome P450 (CYP450) inhibitor, ketoconazole. Formation of 4-OH-BF was greater when treated with 1R-cis-BF compared to the S-enantiomer. However, metabolites were not observed in medaka embryos. These data indicate enantioselective oxidation of BF to an estrogenic metabolite occurs in zebrafish embryos and, since it is increased after liver development, may partially explain estrogenic activity observed in older animals. The lack of activity in medaka suggests species-specific effects with BF metabolism and may influence risk assessment strategies in wildlife.

The increased use of pyrethroid insecticides raises concern for exposure to non-target aquatic species, such as Chinook salmon (Oncorhynchus tshawytscha). Cypermethrin, a type II pyrethroid, is frequently detected in surface waters and sediments at concentrations that exceed levels that induce toxicity to several invertebrate and salmonid species. To better understand the effects of cypermethrin to salmonids following dietary exposure, juvenile Chinook salmon were dietarily exposed to a 0, 200, or 2000 ng/g cypermethrin diet for a duration of 7, 14, or 21 days and assessed for body burden residues, swimming performance, lipid content, and lipid homeostatic gene expression. The average cypermethrin concentrations in fish dietarily exposed to cypermethrin for 21 days were 155.4 and 952.1 ng cypermethrin/g lipid for the 200 and 2000 ng/g pellet treatments, respectively. Increased trends of fatty acid synthase (fasn, r2 = 0.10, p

Antibiotic residues in the aquatic environment have been shown to induce significant adverse effects on the early-life stage development of aquatic organisms, though the underlying molecular mechanisms of these effects have not been well characterized. In this study, we performed global mRNA-miRNA sequencing, canonical pathway analyses, morphological, physiological, immunohistochemical, and behavioral analyses to comprehensively assess the cross-generational cardiotoxicity and mechanisms of antibiotic mixtures in zebrafish. Following parental treatment to 1 and 100 μg/L antibiotic mixtures (15 of the most commonly detected antibiotics) for 150 days, all 15 assessed antibiotics were detected in the F1 eggs, indicating the cross-generational transfer of antibiotics. Global mRNA-miRNA sequencing functional analysis predicted cardiotoxicity in the F1 generation by using the F1 whole fish. Consistent with canonical pathway analyses, significant cardiotoxicity was observed in F1 larvae, as well as the apoptosis of cardiac cells. Furthermore, let-7a-5p regulated the cardiac hypertrophy signaling pathway, suggesting mechanisms of miRNA of let-7 family mediating cross-generational cardiotoxicity of antibiotics in zebrafish. This study lays some groundwork for developing interventions to prevent parental exposure to environmental pollutants such as antibiotics from adversely affecting offspring development.

The pyrethroid insecticide, bifenthrin, is frequently measured at concentrations exceeding those that induce acute and chronic toxicity to several invertebrate and fish species residing in the Sacramento-San Joaquin Delta of California. Since the brain is considered to be a significant target for bifenthrin toxicity, juvenile steelhead trout (Oncorhynchus mykiss) were treated with concentrations of bifenthrin found prior to (60 ng/L) and following (120 ng/L) major stormwater runoff events with nontargeted metabolomics used to target transcriptomic alterations in steelhead brains following exposure. Predicted responses were involved in cellular apoptosis and necrosis in steelhead treated with 60 ng/L bifenthrin using the software Ingenuity Pathway Analysis. These responses were predominately driven by decreased levels of acetyl-l-carnitine (ALC), docosahexaenoic acid (DHA), and adenine. Steelhead treated with 120 ng/L bifenthrin had reductions of lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE), and increased levels of betaine, which were predicted to induce an inflammatory response. Several genes predicted to be involved in apoptotic (caspase3 and nrf2) and inflammatory (miox) pathways had altered expression following exposure to bifenthrin. There was a significantly increased expression of caspase3 and miox in fish treated with 120 ng/L bifenthrin with a significant reduction of nrf2 in fish treated with 60 ng/L bifenthrin. These data indicate that bifenthrin may have multiple targets within the brain that affect general neuron viability, function, and signaling potentially through alterations in signaling fatty acids.

Formation of halogenated disinfection byproducts (DBPs) from pharmaceutically active compounds has been observed in water supply systems following wastewater chlorination. Although research has been limited thus far, several studies have shown that halogenated DBPs may elicit increased toxicity compared to their parent compounds. For example, the lipid regulator gemfibrozil has been shown to form chlorogemfibrozil (Cl-gemfibrozil) and bromogemfibrozil (Br-gemfibrozil) following chlorination, which are more potent antiandrogens in male Japanese medaka (Oryzias latipes) compared to their parent compounds. In the present study, we aimed to characterize the bioaccumulative ability of halogenated gemfibrozil DBPs in marine polychaetes via chronic sediment exposures and, consequently, to assess the chronic and acute toxicity of halogenated gemfibrozil DBPs through sediment (in vivo) and aqueous (in vivo and in silico) toxicity evaluations. Following 28 day sediment exposures, Cl-gemfibrozil and Br-gemfibrozil bioaccumulated within Neanthes arenaceodentata, with both compounds reducing survival and growth. The biota-sediment accumulation factors determined for Cl-gemfibrozil and Br-gemfibrozil were 2.59 and 6.86, respectively. Furthermore, aqueous 96 h toxicity tests with N. arenaceodentata indicated that gemfibrozil DBPs elicited increased toxicity compared to the parent compound. While gemfibrozil had an acute LC50 value of 469.85 ± 0.096 mg/L, Cl-gemfibrozil and Br-gemfibrozil had LC50 values of 12.34 ± 0.085 and 9.54 ± 0.086 mg/L, respectively. Although acute toxicity is relatively low, our results indicate that halogenated gemfibrozil DBPs are bioaccumulative and may elicit effects in apex food web organisms prone to accumulation following lifelong exposures.

Soil is a primary sink for plastics, but the influence of microplastics as carriers on terrestrial cycling of persistent contaminants is poorly understood as compared to aquatic systems. Studies to date have disregarded the potential fact that microplastics are generally contaminated before their entry into soil. In this study, earthworm Eisenia fetida was incubated for 28 d in a soil amended with five common types of microplastics precontaminated with polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) to elucidate contaminant transfer. Accumulation of HOCs in E. fetida varied greatly among different plastic types and HOCs. The freely dissolved concentration (Cfree) of HOCs showed that desorption of HOCs from microplastics into soil was closely related to plastic types and HOC hydrophobicity and was much slower for polystyrene or polypropylene than polyethylene. Biodynamic model analysis suggested that ingestion of microplastics could act as a significant pathway for some microplastics, likely due to HOCs on the plastics being in an "over-equilibrium" state. This was in contrast with mixing clean microplastics into HOC-contaminated soil, where the microplastics decreased bioaccumulation. Therefore, whether microplastics serve as facilitators or inhibitors of HOC bioaccumulation depends on the fugacity gradient of HOCs between microplastics and soil, which highlights the importance of considering the sequence of contamination between the plastics and soil. These findings also question the validity of short-term experiments because of the generally very slow partition kinetics of HOCs on plastics.

Polycyclic aromatic hydrocarbons (PAHs) present in crude oil are known to impair visual development in fish. However, the underlying mechanism of PAH-induced toxicity to the visual system of fish is not understood. Embryonic zebrafish (Danio rerio) at 4 h post fertilization were exposed to weathered crude oil and assessed for visual function using an optokinetic response, with subsequent samples taken for immunohistochemistry and gene expression analysis. Cardiotoxicity was also assessed by measuring the heart rate, stroke volume, and cardiac output, as cardiac performance has been proposed to be a contributing factor to eye-associated malformations following oil exposure. Larvae exposed to the highest concentrations of crude oil (89.8 μg/L) exhibited an increased occurrence of bradycardia, though no changes in stroke volume or cardiac output were observed. However, genes important in eye development and phototransduction were downregulated in oil-exposed larvae, with an increased occurrence of cellular apoptosis, reduced neuronal connection, and reduced optokinetic behavioral response in zebrafish larvae.

Cyclophosphamide, one of the earliest prescribed alkylating anticancer drugs, has been frequently detected in aquatic environments. However, its effects on fish behavior and associated mechanisms remain largely unknown. In this study, the behaviors, neurochemicals, and gut microbiota of adult zebrafish were investigated after 2 months of exposure to CP at 0.05, 0.5, 5, and 50 µg/L. Behavioral assays revealed that CP increased locomotion and anxiety, and decreased the cognition of zebrafish. The alteration of neurotransmitters and related gene expressions in the dopamine and gamma-aminobutyric acid pathways induced by CP may be responsible for the observed changes in locomotion and cognition of adult zebrafish. Meanwhile, CP increased the anxiety of adult zebrafish through the serotonin, acetylcholine, and histamine pathways in the brain. In addition, increased abundances of Fusobacteriales, Reyanellales, Staphylococcales, Rhodobacterals, and Patescibateria in the intestine at the CP-50 treatment were observed. The study has demonstrated that CP affects the locomotion, anxiety, and cognition in zebrafish, which might be linked with the dysfunction of neurochemicals in the brain. This study further suggests that the gut-brain axis might interact to modulate fish behaviors upon exposure to CP (maybe other organic pollutants). Further research is warranted to test this hypothesis.

The extensive and increasing global use of antibiotics results in the ubiquitous presence of antibiotics in the environment, which has made them “pseudo persistent organic contaminants.” Despite numerous studies showing wide adverse effects of antibiotics on organisms, the chronic environmental risk of their exposure is unknown, and the molecular and cellular mechanisms of antibiotic toxicity remain unclear. Here, we systematically quantified transgenerational immune disturbances after chronic parental exposure to environmental levels of a common antibiotic, chlortetracycline (CTC), using zebrafish as a model. CTC strongly reduced the antibacterial activities of fish offspring by transgenerational immunosuppression. Both innate and adaptive immunities of the offspring were suppressed, showing significant perturbation of macrophages and neutrophils, expression of immune-related genes, and other immune functions. Moreover, these CTC-induced immune effects were either prevented or alleviated by the supplementation with PDTC, an antagonist of nuclear factor-κB (NF-κB), uncovering a seminal role of NF-κB in CTC immunotoxicity. Our results provide the evidence in fish that CTC at environmentally relevant concentrations can be transmitted over multiple generations and weaken the immune defense of offspring, raising concerns on the population hazards and ecological risk of antibiotics in the natural environment.

The continual discharge of pharmaceuticals from wastewater treatment plants (WWTPs) into the marine environment, even at concentrations as low as ng/L, can exceed levels that induce sublethal effects to aquatic organisms. Amitriptyline, a tricyclic antidepressant, is the most prescribed antidepressant in Norway, though the presence, potential for transport, and uptake by aquatic biota have not been assessed. To better understand the release and bioaccumulative capacity of amitriptyline, laboratory exposure studies were carried out with field-collected sediments. Influent and effluent composite samples from the WWTP of Stavanger (the 4th largest city in Norway) were taken, and sediment samples were collected in three sites in the proximity of this WWTP discharge at sea (WWTP discharge (IVAR), Boknafjord, and Kvitsøy (reference)). Polychaetes (Nereis virens) were exposed to field-collected sediments, as well as to Kvitsøy sediment spiked with 3 and 30 μg/g amitriptyline for 28 days. The WWTP influent and effluent samples had concentrations of amitriptyline of 4.93 ± 1.40 and 6.24 ± 1.39 ng/L, respectively. Sediment samples collected from IVAR, Boknafjord, and Kvitsøy had concentrations of 6.5 ± 3.9, 15.6 ± 12.7, and 12.7 ± 8.0 ng/g, respectively. Concentrations of amitriptyline were below the limit of detection in polychaetes exposed to sediment collected from Kvitsøy and IVAR, and 5.2 ± 2.8 ng/g in those exposed to Boknafjord sediment. Sediment spiked with 3 and 30 μg/g amitriptyline had measured values of 423.83 ± 33.1 and 763.2 ± 180.5 ng/g, respectively. Concentrations in worms exposed to the amended sediments were 9.5 ± 0.2 and 56.6 ± 2.2 ng/g, respectively. This is the first known study to detect measurable concentrations of amitriptyline in WWTP discharge in Norway and accumulation in polychaetes treated with field-collected sediments, suggesting that amitriptyline has the potential for trophic transfer in marine systems.

The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 μg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.

Projected water temperature increases based on predicted climate change scenarios and concomitant pesticide exposure raises concern about the responses of aquatic organisms. To better understand the effect of pesticide mixtures and influence of water temperature to fish, juvenile Chinook salmon (Oncorhynchus tshawytscha) were dietarily exposed to a mixture of legacy and current use pesticides (p,p'-DDE, bifenthrin, chlorpyrifos, esfenvalerate, and fipronil) at concentrations detected from field-collected prey items in the Sacramento-San Joaquin Delta, California (Delta) and exposed under current and predicted future water temperature scenarios, 11, 14, or 17 °C, for 14 days. The expression of a subset of genes (deiodinase 2-dio2, gonadotropin releasing hormone 2-gnrh2, and catechol-o-methyltransferase-comt) involved in neuroendocrine, dopaminergic, and olfactory function previously shown to be altered by individual pesticide exposures germane to this study were determined and olfactory function assessed using a Y-maze behavioral assay. When total body burdens of pesticides were measured, a significant decrease in dio2 expression was observed in Chinook salmon exposed at 14 °C compared to fish kept at 11 °C. Increases in gnrh2 expression were also observed in fish exposed to 14 °C. Similarly, increases in comt expression was noted at 14 and 17 °C. Additionally, altered expression of all transcripts was observed, showing interactions between temperature and individual pesticide concentrations. Chinook salmon spent significantly more time actively avoiding the odorant arm at baseline conditions of 11 °C in the Y-maze. At higher temperatures, Chinook spent significantly more time not making a choice between the odorant or clean arm following exposure to the low pesticide mixture, relative to 11 °C. These results suggest that dietary exposure to pesticide mixtures can potentially induce neuroendocrine effects and behavior. Impaired olfactory responses exhibited by Chinook salmon could have implications for predator avoidance in the wild under increased temperature scenarios and impact populations in the future.

Excess dietary seleno-l-methionine (Se-Met) induces various adverse effects in fish inhabiting the Se-contaminated environments. However, there is an extreme paucity of data on the effects of excess dietary Se-Met on the microbiota in the gastrointestinal (GI) tract in fish. In this study, Japanese medaka

Dysregulation of microRNA (miRNA, miR) by environmental stressors influences the transcription of mRNA which may impair organism development and/or lead to adverse physiological outcomes. Early studies evaluating the effects of oil on developmental toxicity in early life stages of fish showed that reductions in expression of miR-203a were associated with enhanced expression of downstream mRNAs that predicted altered eye development, cardiovascular disease, and improper fin development. To better understand the effects of miR-203a inhibition as an outcome of oil-induced toxicity in early life stage (ELS) fish, embryonic zebrafish were injected with an miR-203a inhibitor or treated with 3.5 µM phenanthrene (Phe) as a positive control for morphological alterations of cardiovascular and eye development caused by oil. Embryos treated with Phe had diminished levels of miR-203a at 7 and 72 h after injection. Embryos treated with the miR-203a inhibitor and Phe exhibited a reduced heart rate by 48 h post fertilization (hpf), with an increased incidence of developmental deformities (including pericardial edema, altered eye development, and spinal deformities) and reduced caudal fin length by 72 hpf. There were significant reductions in lens and eye diameters in 120 hpf miR-203a-inhibitor and Phe-treated fish, as well as a significantly reduced number of eye saccades, determined by an optokinetic response (OKR) behavioral assay. The expression of

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely – monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

Aquatic organisms are exposed to complex mixtures of pesticides in the environment, but traditional risk assessment approaches typically only consider individual compounds. In conjunction with exposure to pesticide mixtures, global climate change is anticipated to alter thermal regimes of waterways, leading to potential co-exposure of biota to elevated temperatures and contaminants. Furthermore, most studies utilize aqueous exposures, whereas the dietary route of exposure may be more important for fish owing to the hydrophobicity of many pesticides. Consequently, the current study aimed to determine the effects of elevated temperatures and dietary pesticide mixtures on swimming performance and lipid metabolism of juvenile Chinook salmon, Oncorhynchus tshawytscha. Fish were fed pesticide-dosed pellets at three concentrations and three temperatures (11, 14 and 17 °C) for 14 days and swimming performance (U

Previous studies have shown that altered expression of a family of small noncoding RNAs (microRNAs, or miRs) regulates the expression of downstream mRNAs and is associated with diseases and developmental disorders. miR133b is highly expressed in mammalian cardiac and skeletal muscle, and aberrant expression is associated with cardiac disorders and electrophysiological changes in cardiomyocytes. Similarly, cardiac dysfunction has been observed in early life-stage mahi-mahi (

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish (Danio rerio) was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) μg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.

Crude oil has multiple toxic effects in fish, particularly early life stages. Recent transcriptomics studies have highlighted a potential effect on cholesterol homeostasis and biosynthesis, but have not investigated effects on steroid hormones, which are biosynthetically downstream metabolites of cholesterol. We exposed zebrafish (Danio rerio) embryos and larvae to 3 concentrations of a high energy water accommodated fraction (HEWAF) of crude oil and measured effects on cholesterol and steroid hormones at 48 and 96 hours post fertilization (hpf). HEWAF exposure caused a small decrease in cholesterol at 96 hpf but not 48 hpf. HEWAF-exposed larvae had higher levels of androstenedione, testosterone, estradiol, cortisol, corticosterone, and progesterone at 96 hpf compared to controls, while effects at 48 hpf were more modest or not present. 2-Methoxyestradiol was lower following HEWAF exposure at both time points. Dihydrotestosterone was elevated in one HEWAF concentration at 48 hpf only. Our results suggest that hormone imbalance may be an important toxic effect of oil HEWAF exposure despite no major effect on their biosynthetic precursor cholesterol.

Bisphenol S (BPS), an alternative for bisphenol A (BPA) that is present in thermal paper and numerous consumer products, has been linked to estrogenic, cytotoxic, genotoxic, neurotoxic, and immunotoxic responses. However, the mechanisms of BPS toxicity remain poorly understood. Here, following exposure to environmentally relevant concentrations ranging from 0.1 to 100 μg/L BPS, transcriptional changes evaluated by enriched gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) predicted cardiac disease and impairment of immune function in zebrafish at the embryo-to-larvae stage. Consistent with impacts predicted by transcriptional changes, significant sublethal impacts were observed ranging from reduced heart rate [8.7 ± 2.4% reductions at 100 μg/L BPS treatment; P < 0.05] to abnormal cardiac morphology [atrial/ventricle area significantly increased; 36.2 ± 9.6% at 100 μg/L BPS treatment; P < 0.05]. RNA-sequencing analysis results also indicated changes in nitric oxide synthetase (NOS2) and interleukin 12 (IL12) after BPS treatment, which was confirmed at the protein level. Increased expression of other cytokine genes was observed in larvae, suggesting inflammatory responses may be contributing to cardiac impairment by BPS. BPS caused cardiotoxicity, which temporally corresponded with inflammatory responses as predicted from RNA sequencing and confirmed at the protein and cellular levels of biological organization. Additional study is needed to find causal linkages between these responses.

Crude oil-derived polycyclic aromatic hydrocarbons (PAHs) are pervasive environmental pollutants with well-established detrimental effects on the health of marine organisms. Following large-scale oil spills in the marine environment, there is a critical need for noninvasive sampling methods to assess environmental exposure to PAHs without further perturbations to the population and for long-term monitoring following a spill. To test the efficacy of epidermal mucus mRNA as a source for noninvasive sampling, juvenile mahi-mahi (Coryphaena hippurus, ∼28 days of age) were exposed to control seawater or two concentrations of high-energy water accommodated fractions (HEWAFs; 5% or 10%) of Deepwater Horizon surface oil for 48 h. Whole-transcriptome sequencing revealed differential expression of 501 transcripts in the low-HEWAF exposure (∑PAH = 16.55 μg/L) and 196 transcripts in the high-HEWAF exposure (∑PAH = 23.03 μg/L), suggesting differential regulation of mRNA in mucus following PAH exposure. In addition to ...

Chlorpyrifos is an organophosphorus insecticide that elicits acute toxicity through inhibition of acetylcholinesterase (AChE), leading to acetylcholine accumulation and prolonged stimulation of cholinergic receptors throughout the central and peripheral nervous systems. Previous studies have indicated that neurodevelopment may also be impaired through alternative pathways, including reduction of cyclic adenosine monophosphate (cAMP)-catalyzed downstream events. The upstream initiating events that underlie noncholinergic neurological actions of chlorpyrifos and other organophosphorus compounds remain unclear. To investigate the potential role of fatty acid signaling disruption as a mechanism of toxicity, lipid metabolism and fatty acid profiles were examined to identify alterations that may play a critical role in upstream signaling in the central nervous system (CNS). Juvenile rainbow trout were treated for 7 days with nominal chlorpyrifos concentrations previously reported to diminish olfactory responses (10, 20, and 40 μg/l). Although lethality was noted higher in doses, measured chlorpyrifos concentrations of 1.38 μg/l (nominal concentration 10 μg/l) significantly reduced the activity of AChE and two serine lipases, monoacylglycerol lipase, and fatty acid amide hydrolase in the brain. Reductions in lysophosphatidylethanolamines (16:0, 18:0, 18:1, and 22:6) derived from the phosphatidylethanolamines and free fatty acids (palmitic acid 16:0, linolenic acid 18:3, eicosadienoic acid 20:2, arachidonic acid 20:4, and docosahexaenoic acid 22:6) were also noted, suggesting that chlorpyrifos inhibited the metabolism of select phospholipid signaling precursors at sublethal concentrations. These results indicate that in addition to AChE inhibition, environmentally relevant chlorpyrifos exposure alters serine lipase activity and lipid metabolites in the trout brain, which may compromise neuronal signaling and impact neurobehavioral responses in aquatic animals.

Ecotoxicological risks of neonicotinoid insecticides are raising significant concerns, including their potential role in bee population declines. Neonicotinoids are water-soluble, systemic insecticides, and exposure of nontarget organisms such as pollinators occurs mainly through residues in nectar and pollens of flowering plants. To better elucidate the underlying mechanisms for such nontarget exposure, it is highly valuable to develop analytical capabilities for in vivo monitoring of neonicotinoids in live plants. In this study, we developed a novel biomimetic water-swelling solid-phase microextraction (SPME) probe, with limits of detection for neonicotinoids as low as 0.03 ng mL-1, and applied it for in vivo detection of seven neonicotinoids in plant sap. The preparation of this fiber was simple and free of stringent or complex physical-chemical reactions. Equilibrium in neonicotinoid accumulation on the fiber was reached in

Organophosphate esters (OPEs) have been in use as flame retardants for many decades, with their actual usage varying over time. Knowledge of the emission history of OPEs is valuable for improving our prediction of their environmental loadings and associated risks. In this study, concentrations and compositions of 10 OPEs were measured in three dated sediment cores from the Palos Verdes Shelf (PVS) off the coast of Los Angeles, which has been impacted by wastewater treatment plant (WWTP) effluents for over a century. The total OPE concentrations varied from 0.68 to 1064 ng/g along the sediment profile, with two apparent peaks. The first peak occurred in the 1970s, coinciding with peak emissions from WWTPs. The second peak appeared in the 2000s and was possibly attributed to increased consumption of OPEs as replacement flame retardants. Since downward movement of OPEs in the PVS sediment bed was retarded by their slow desorption, the reconstructed history likely provided an accurate picture of OPE emissions in Southern California and North America. These findings suggest that the near-shore marine sediments affected by WWTP effluents could serve as an environmental proxy documenting history in OPE use and emissions.

Smoked cigarettes are the most prevalent form of litter worldwide, often finding their way into oceans and inland waterways. Cigarette smoke contains more than 4000 individual chemicals, some of them carcinogenic or otherwise toxic. We examined the cytotoxicity, genotoxicity, aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and p53 response pathways of smoked cigarette leachate in vitro. Both seawater and freshwater leachates of smoked cigarettes were tested. Cytotoxicity and genotoxicity were negligible at 100 smoked cigarettes/L, while statistically significant AhR, ER, and p53 responses were observed in the extracts of both leachates, suggesting a potential risk to human health through exposure to cigarette litter in the environment. To identify responsible chemicals for the AhR response, an effect directed analysis approach was coupled with nontargeted chemical analysis based on comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC/TOF-MS). Eleve...