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1.
Article in English | MEDLINE | ID: mdl-38888255

ABSTRACT

Despite decades of fate and effects studies, environmental selenium (Se) contamination and management remain an issue for many freshwater systems in North America. Several regulatory bodies have promulgated updated targets or management levels for Se; however, additional guidance on best practices for monitoring Se to protect freshwater aquatic life is warranted. In this article, we describe current approaches to assessing the ecological risks of Se in impaired freshwater systems and outline recommended methods for collecting and analyzing biological and abiotic samples and interpreting data. Because reproductive impairment of fish populations is most commonly used to determine the potential impacts of Se, several biological factors that could affect Se toxicity are explored, including diet, trophic positions, reproductive biology, body size and maturity, migratory movements, and use of seasonal habitats. Measuring Se concentrations in mature eggs is the most reliable metric for estimating potential reproductive impairment in fish populations because the range of toxicity thresholds is relatively narrow for all but a few tolerant fish species. In situations where collecting mature eggs is not feasible, we review the use of alternative fish tissue for estimating potential effects. Factors affecting Se uptake from freshwater are also considered with guidance on collecting abiotic (e.g., water and sediment) and biotic components of aquatic food webs (e.g., macroinvertebrates, biofilm). Integr Environ Assess Manag 2024;00:1-16. © 2024 SETAC.

2.
Article in English | MEDLINE | ID: mdl-38041586

ABSTRACT

In the Lake Koocanusa-Kootenai River system (Montana, USA and British Columbia, Canada), selenium (Se) contamination has become an international concern and is suspected to contribute to the observed burbot (Lota lota) population collapse. Due to our limited ability to sample burbot in Lake Koocanusa for monitoring studies, we used a reference population to develop tools to model tissue Se disposition for a focal species in systems with elevated Se. Total Se concentrations in otoliths, biofluids (blood and endolymph), and tissues (muscle, liver, and ovary) from burbot in reference lakes in northwestern Ontario, Canada, were measured to document tissue-to-tissue Se relationships and evaluate the potential for otoliths to retrace Se exposure in fish. Among burbot tissue, Se concentrations were the highest in the ovary (mean ± SD = 4.55 ± 2.23 µg g-1 dry mass [dm]), followed by the liver (2.69 ± 1.96 µg g-1 dm) and muscle (1.87 ± 1.14 µg g-1 dm), and decreased with body size (p < 0.05). In otoliths, Se was detected at low levels (<1 µg g-1 ). Selenium concentrations in burbot samples were positively correlated among muscle, ovary, liver, and endolymph tissues, but not for the most recent annually averaged or lifetime-averaged Se concentrations in otoliths. We hypothesize that Se concentrations were too low in this study to establish links between otoliths and other fish tissues and to detect significant lifetime variation in individuals, and that further validation using archived otoliths from burbot exposed to elevated Se levels in Lake Koocanusa-Kootenai River is needed to reconstruct exposure histories. However, intercompartmental models proved valuable for estimating Se concentrations in burbot tissues only available by means of lethal sampling (i.e., ovary), although additional work should confirm whether the established models are reliable to predict concentrations in Se-impaired systems as tissue distributions are likely to differ with increasing Se levels. Integr Environ Assess Manag 2023;00:1-11. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

3.
Chemosphere ; 329: 138608, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37028727

ABSTRACT

Following an oil spill into water, bacteria can biodegrade petroleum hydrocarbons which could lead to petrogenic carbon assimilation by aquatic biota. We used changes in the isotope ratios of radio- (Δ14C) and stable (δ13C) carbon to examine the potential for assimilation of petrogenic carbon into a freshwater food web following experimental spills of diluted bitumen (dilbit) into a boreal lake in northwestern Ontario, Canada. Different volumes (1.5, 2.9, 5.5, 18, 42, 82, and 180 L) of Cold Lake Winter Blend (a heavy crude blend of bitumen and condensate) dilbit were applied to seven 10-m diameter littoral limnocorrals (approximate volume of 100 m3), and two additional limnocorrals had no added dilbit to serve as controls. Particulate organic matter (POM) and periphyton from oil-treated limnocorrals had lower δ13C (up to 3.2‰ and 2.1‰ for POM and periphyton, respectively) than the control at every sampled interval (3, 6 and 10 weeks for POM and 6, 8 and 10 weeks for periphyton). Dissolved organic and inorganic carbon (DOC and DIC, respectively) had lower Δ14C in the oil-treated limnocorrals relative to the control (up to 122‰ and 440‰ lower, respectively). Giant floater mussel (Pyganodon grandis) housed for 25 days in aquaria containing oil-contaminated water from the limnocorrals did not show significant changes in δ13C values of muscle tissue compared to mussels housed in control water. Overall, the changes in δ13C and Δ14C observed indicated small amounts (up to 11% in DIC) of oil carbon incorporation into the food web. The combined δ13C and Δ14C data provide evidence for minimal incorporation of dilbit into the food web of this oligotrophic lake, suggesting that microbial degradation and subsequent incorporation of oil C into the food web may play a relatively small role in the ultimate fate of oil in this type of ecosystem.


Subject(s)
Carbon , Food Chain , Hydrocarbons , Water Pollutants, Chemical , Carbon Isotopes/analysis , Ecosystem , Lakes , Ontario , Water , Water Pollutants, Chemical/analysis
4.
Environ Pollut ; 305: 119304, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35430311

ABSTRACT

The largest and most variable step of selenium (Se) assimilation into aquatic ecosystems is the rapid uptake of aqueous Se by primary producers. These organisms can transfer more harmful forms of Se to higher trophic levels via dietary pathways, although much uncertainty remains around this step of Se assimilation due to site-specific differences in water chemistry, hydrological and biogeochemical characteristics, and community composition. Thus, predictions of Se accumulation are difficult, and boreal lake systems are relatively understudied. To address these knowledge gaps, five static-renewal field experiments were performed to examine the bioaccumulation of low, environmentally relevant concentrations of Se, as selenite, by naturally grown periphyton from multiple boreal lakes. Periphyton rapidly accumulated Se at low aqueous Se concentrations, with tissue Se concentrations ranging from 8.0 to 24.9 µg/g dry mass (dm) in the 1-2 µg Se/L treatments. Enrichment functions ranged from 2870 to 12 536 L/kg dm in the 4 µg Se/L treatment, to 11 867-22 653 L/kg dm in the 0.5 µg Se/L treatment among lakes. Periphyton Se uptake differed among the five study lakes, with periphyton from mesotrophic lakes generally accumulating more Se than periphyton from oligotrophic lakes. Higher proportions of charophytes and greater dissolved inorganic carbon in more oligotrophic lakes corresponded to less periphyton Se uptake. Conversely, increased proportions of bacillariophytes and total dissolved phosphorus in more mesotrophic lakes corresponded to greater periphyton Se uptake. Periphyton community composition and water chemistry variables were correlated, limiting interpretation of differences in periphyton Se accumulation among lakes. The results of this research provide insight on the biodynamics of Se assimilation at the base of boreal lake food webs at environmentally relevant concentrations, which can potentially inform ecological risk assessments in boreal lake ecosystems in North America.


Subject(s)
Periphyton , Selenium , Water Pollutants, Chemical , Ecosystem , Food Chain , Lakes/chemistry , Selenium/metabolism , Water , Water Pollutants, Chemical/analysis
5.
Environ Res ; 212(Pt A): 113151, 2022 09.
Article in English | MEDLINE | ID: mdl-35318011

ABSTRACT

Selenium (Se) is an environmental contaminant of global concern that can cause adverse effects in fish at elevated levels. Fish gut microbiome play essential roles in gastrointestinal function and host health and can be perturbed by environmental contaminants, including metals and metalloids. Here, an in-situ Se exposure of female finescale dace (Phoxinus neogaeus) using mesocosms was conducted to determine the impacts of Se accumulation on the gut microbiome and morphometric endpoints. Prior to this study, the gut microbiome of finescale dace, a widespread Cyprinid throughout North America, had not been characterized. Exposure to Se caused a hormetic response of alpha diversity of the gut microbiome, with greater diversity at the lesser concentration of 1.6 µg Se/L, relative to that of fish exposed to the greater concentration of 5.6 µg Se/L. Select gut microbiome taxa of fish were differentially abundant between aqueous exposure concentrations and significantly correlated with liver-somatic index (LSI). The potential effects of gut microbiome dysbiosis on condition of wild fish might be a consideration when assessing adverse effects of Se in aquatic environments. More research regarding effects of Se on field-collected fish gut microbiome and the potential adverse effects or benefits on the host is warranted.


Subject(s)
Cyprinidae , Gastrointestinal Microbiome , Selenium , Animals , Cyprinidae/physiology , Female , Metals , North America , Selenium/analysis , Selenium/toxicity
6.
Environ Toxicol Chem ; 41(1): 95-107, 2022 01.
Article in English | MEDLINE | ID: mdl-34808000

ABSTRACT

Selenium (Se) is a contaminant of concern in Canada mainly due to its teratogenic effects on fish and birds. However, few studies have assessed the effects of Se on invertebrates in a field setting. The objective of this experiment was to assess potential community-level impacts of Se additions on zooplankton and benthic macroinvertebrates in a boreal lake ecosystem. From June to August 2018, Se (as selenite) was added to six limnocorrals in Lake 239 at the International Institute for Sustainable Development-Experimental Lakes Area, Northwestern Ontario, Canada, to achieve mean measured aqueous concentrations of 0.4, 0.8, 1.6, 3.4, 5.6 and 7.9 µg Se/L, with three untreated limnocorrals serving as controls (background Se = 0.08-0.09 µg/L). Periphyton, phytoplankton, and invertebrates (zooplankton and benthos) were monitored for 63 days. Zooplankton community composition shifted as a function of Se exposure, with Cladocera biomass and density decreasing with increasing Se concentrations. Similarly, cumulative abundance and biomass of Heptageniidae decreased with increasing Se treatment throughout the experimental period. The present study demonstrated that Se can have impacts on aquatic invertebrates at environmentally relevant exposure levels, and that future ecological risk assessments should consider the impacts of Se on both vertebrates and invertebrates. Environ Toxicol Chem 2022;41:95-107. © 2021 SETAC.


Subject(s)
Cladocera , Selenium , Water Pollutants, Chemical , Animals , Ecosystem , Invertebrates , Lakes , Ontario , Phytoplankton , Selenium/analysis , Selenium/toxicity , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Zooplankton
7.
Environ Pollut ; 280: 116956, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33799129

ABSTRACT

Selenium (Se) is both an essential micronutrient and a contaminant of concern that is of particular interest in mining-influenced waterbodies in Canada. The objective of this research was to characterize the trophic dynamics of selenium along a gradient of exposure concentrations in a Canadian boreal lake ecosystem. From June 20 to August 22, 2018, six limnocorrals (littoral, ∼3000 L enclosures) were spiked with mean measured concentrations of 0.4, 0.8, 1.6, 3.4, 5.6 and 7.9 µg Se/L as selenite, and three limnocorrals served as untreated controls (background aqueous Se = 0.08-0.09 µg/L). Total Se (TSe) concentrations in water, periphyton, phytoplankton, sediment, benthic macroinvertebrates, zooplankton and female finescale dace (Phoxinus neogaeus; added on day 21 of the experiment) were measured throughout and at the end of the experiment. Total Se bioaccumulation by organisms was generally non-linear. Greater uptake by phytoplankton than periphyton was observed. Taxonomic differences in accumulation of TSe by invertebrates (Heptageniidae = Chironomidae > zooplankton) were observed as well. Fish muscle and ovary tissue TSe bioaccumulation was more variable than that at lower trophic levels and uptake patterns indicated that fish did not reach steady state concentrations. This research provides field-derived models for the uptake of Se by algae and invertebrates, and contributes to a better understanding of the dynamics of TSe bioaccumulation over a gradient of exposure concentrations in cold-water lentic systems.


Subject(s)
Selenium , Water Pollutants, Chemical , Animals , Canada , Ecosystem , Female , Food Chain , Lakes , Selenium/analysis , Water Pollutants, Chemical/analysis
8.
Environ Toxicol Chem ; 39(8): 1608-1619, 2020 08.
Article in English | MEDLINE | ID: mdl-32692460

ABSTRACT

Leeches are widespread, found in many freshwater habitats, and have diverse dietary habits. Despite their close phylogenetic relationships to Mollusca, a phylum with species affected by exogenous estrogens, it is unclear whether Hirudinea may also be impacted. A whole-lake experiment was done at the Experimental Lakes Area in Ontario, Canada, to assess whether 17α-ethynylestradiol (EE2) affected fishes and other species. Herein, we examined whether EE2 impacted leech community composition, species abundance, growth rates, gonad size, and cocoon production, when compared with reference lakes using a before-after-control-impact design. Each month baited leech traps were set overnight in the littoral zone at 10 sites around experimental Lake 260 and 2 reference lakes, and individuals were identified, weighed, and measured. Male and female organs of common species Haemopis marmorata were measured. Across all lakes, 9 species representing 3 families were collected. There were no apparent effects of EE2 on numbers, species richness, or community composition; however, condition in 1 of 5 species increased significantly after EE2 exposures. Total gonadosomatic index (GSI) and the GSI for all male or all female organs combined for H. marmorata were not affected by EE2 additions. However, some individual reproductive organs including relative sperm sac length (+), relative epididymis weight (-), relative vaginal bulb length (+), and relative ovisac + albumen gland length (+) changed after EE2 additions. Finally, whereas overall cocoon production was similar, it occurred earlier in the EE2-amended lake. In summary, few individual through community measures of leeches responded to low ng/L concentrations of EE2, suggesting that Hirudinea are less sensitive to this endocrine disruptor than other invertebrates and vertebrates. Environ Toxicol Chem 2020;39:1608-1619. © 2020 SETAC.


Subject(s)
Ethinyl Estradiol/toxicity , Lakes/chemistry , Leeches/drug effects , Animals , Endocrine Disruptors/pharmacology , Female , Gonads/drug effects , Male , Ontario , Species Specificity , Water Pollutants, Chemical/analysis
9.
Plants (Basel) ; 9(4)2020 Apr 19.
Article in English | MEDLINE | ID: mdl-32325841

ABSTRACT

Selenium (Se) uptake by primary producers is the most variable and important step in determining Se concentrations at higher trophic levels in aquatic food webs. We gathered data available about the Se bioaccumulation at the base of aquatic food webs and analyzed its relationship with Se concentrations in water. This important dataset was separated into lotic and lentic systems to provide a reliable model to estimate Se in primary producers from aqueous exposure. We observed that lentic systems had higher organic selenium and selenite concentrations than in lotic systems and selenate concentrations were higher in lotic environments. Selenium uptake by algae is mostly driven by Se concentrations, speciation and competition with other anions, and is as well influenced by pH. Based on Se species uptake by algae in the laboratory, we proposed an accurate mechanistic model of competition between sulfate and inorganic Se species at algal uptake sites. Intracellular Se transformations and incorporation into selenoproteins as well as the mechanisms through which Se can induce toxicity in algae has also been reviewed. We provided a new tool for risk assessment strategies to better predict accumulation in primary consumers and consequently to higher trophic levels, and we identified some research needs that could fill knowledge gaps.

10.
Ecotoxicol Environ Saf ; 182: 109354, 2019 Oct 30.
Article in English | MEDLINE | ID: mdl-31272025

ABSTRACT

Selenium (Se) is a contaminant of concern in many aquatic ecosystems due to its narrow range between essentiality and toxicity in oviparous (yolk-bearing) vertebrates. The objective of the present study was to determine the effects of Se, experimentally added to in situ limnocorrals as selenite, on invertebrate communities and fathead minnow (Pimephales promelas) at environmentally realistic Se concentrations. Nine limnocorrals were deployed in a mesotrophic lake at the International Institute for Sustainable Development - Experimental Lakes Area in Ontario, Canada in May 2017. From June 1 to August 17, 2017, selenite was added to six enclosures to attain mean measured aqueous Se concentrations of 1.0 ±â€¯0.10 or 8.9 ±â€¯2.7 µg/L Se (in triplicate) and three limnocorrals were untreated controls (background mean aqueous Se = 0.12 ±â€¯0.03 µg/L). Benthic macroinvertebrates were collected throughout and at the end of the exposure period using artificial substrates to determine density, dry biomass, diversity, and taxa richness at the family level. Reproductively mature female fathead minnows (added on d 33 of the study) were collected throughout and at the end of the exposure period. After 77 d, Chironomidae and Gammaridae densities and biomass were significantly lower in the 8.9 µg/L Se treatment relative to the 1.0 µg/L Se treatment and the control. Invertebrate diversity (measured as Shannon's and Simpson's indices) significantly declined in the 1.0 µg/L and 8.9 µg/L Se treatments relative to the control (0.12 µg/L Se group). Fulton's condition factor for fathead minnow was significantly less in the 8.9 µg/L treatment compared to 0.12 and 1.0 µg/L Se experimental groups. The results of this study indicated that exposure to relatively low aqueous selenite concentrations can negatively affect invertebrate density and biomass, as well as fish condition. More research is necessary to characterize the risk of selenite exposure to aquatic invertebrates under realistic field conditions, and future risk assessments may need to consider reduced food availability as a factor that may impair the health of higher trophic level organisms in areas with elevated selenite.


Subject(s)
Ecosystem , Selenium/toxicity , Water Pollutants, Chemical/toxicity , Animals , Aquatic Organisms/physiology , Chironomidae , Cyprinidae/physiology , Female , Invertebrates/physiology , Lakes , Ontario , Reproduction/drug effects , Selenious Acid/toxicity
11.
Environ Toxicol Chem ; 38(9): 1954-1966, 2019 09.
Article in English | MEDLINE | ID: mdl-31145497

ABSTRACT

Human activities have increased the release of selenium (Se) to aquatic environments, but information about the trophic transfer dynamics of Se in Canadian boreal lake systems is limited. In the present study, Se was added as selenite to limnocorrals (2-m-diameter, 3000-L in situ enclosures) in a boreal lake in northwestern Ontario to reach nominal concentrations of 1 and 10 µg Se/L in triplicate each for 77 d, and 3 additional limnocorrals were controls with no Se added. Total Se concentrations were determined in water, sediment, periphyton, benthic macroinvertebrates, zooplankton, and reproductively mature female fathead minnows (Pimephales promelas; added on day 33) collected throughout (and at the end of) the exposure period. Mean measured water Se concentrations in the control, 1-, and 10-µg/L treatments were 0.12, 1.0, and 8.9 µg/L. At the end of exposure (day 77), enrichment functions ranged from 7772 L/kg dry mass in the 8.9-µg/L treatment to 23 495 L/kg dry mass in the 0.12-µg/L treatment, and trophic transfer factors for benthic macroinvertebrates ranged from 0.49 for Gammaridae to 2.3 for Chironomidae. Selenium accumulated in fathead minnow ovaries to concentrations near or above the current US Environmental Protection Agency criterion (15.1 µg/g dry mass for fish ovary/egg) in the 1.0- and 8.9-µg/L treatments, suggesting that, depending on aqueous Se speciation, such exposures have the potential to cause Se accumulation in fish to levels of concern in cold-water, boreal lake systems. Environ Toxicol Chem 2019;38:1954-1966. © 2019 SETAC.


Subject(s)
Ecosystem , Lakes/chemistry , Selenium/metabolism , Animals , Chironomidae/growth & development , Cyprinidae/metabolism , Female , Food Chain , Geologic Sediments/analysis , Larva/chemistry , Muscles/chemistry , Muscles/metabolism , Selenium/chemistry
12.
Med Princ Pract ; 28(1): 91-95, 2019.
Article in English | MEDLINE | ID: mdl-30355921

ABSTRACT

OBJECTIVE: To present a case of Hashimoto encephalopathy as a complication of autoimmune thyroiditis. CLINICAL PRESENTATION AND INTERVENTION: A previously healthy 56-year-old female presented with rapidly progressive cognitive decline and visual hallucinations. Being a diagnosis of exclusion, Hashimoto encephalopathy required an extensive laboratory and diagnostic workup, which was done over the course of a 15-day hospitalization. The patient recovered after initial treatment with intravenous methylprednisolone and was then switched to prednisone p.o. CONCLUSION: This case report illustrates the importance of awareness for Hashimoto encephalopathy, as it remains one of the few easily treatable and reversible causes of rapid cognitive decline.


Subject(s)
Encephalitis/complications , Hashimoto Disease/complications , Thyroiditis, Autoimmune/complications , Anti-Inflammatory Agents/therapeutic use , Encephalitis/diagnosis , Encephalitis/drug therapy , Female , Hashimoto Disease/diagnosis , Hashimoto Disease/drug therapy , Humans , Methylprednisolone/therapeutic use , Middle Aged , Treatment Outcome
13.
Article in English | MEDLINE | ID: mdl-27939725

ABSTRACT

Methylmercury (MeHg) exposure and adverse health effects in fishes have been documented, but the molecular mechanisms involved in toxicity have not been fully characterized. The objectives of the current study were to (1) determine whether total Hg (THg) in the muscle was predictive of MeHg concentrations in the brain of wild female yellow perch (Perca flavescens) collected from four lakes in Kejimkujik National Park, a known biological mercury (Hg) hotspot in Nova Scotia, Canada and (2) to determine whether transcripts involved in the oxidative stress response were altered in abundance in fish collected across five lakes representing a MeHg gradient. In female yellow perch, MeHg in whole brain (0.38 to 2.00µg/g wet weight) was positively associated with THg in muscle (0.18 to 2.13µg/g wet weight) (R2=0.61, p<0.01), suggesting that muscle THg may be useful for predicting MeHg concentrations in the brain. Catalase (cat) mRNA levels were significantly lower in brains of perch collected from lakes with high Hg when compared to those individuals from lakes with relatively lower Hg (p=0.02). Other transcripts (cytochrome c oxidase, glutathione peroxidase, glutathione-s-transferase, heat shock protein 70, protein disulfide isomerase, and superoxide dismutase) did not show differential expression in the brain over the gradient. These findings suggest that MeHg may be inversely associated with catalase mRNA abundance in the central nervous system of wild fishes.


Subject(s)
Brain/drug effects , Catalase/genetics , Fish Proteins/genetics , Methylmercury Compounds/toxicity , Oxidative Stress/drug effects , Perches/genetics , RNA, Messenger/genetics , Water Pollutants, Chemical/toxicity , Animals , Body Burden , Brain/metabolism , Catalase/metabolism , Down-Regulation , Environmental Monitoring/methods , Female , Fish Proteins/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Genetic Markers , Methylmercury Compounds/metabolism , Muscle, Skeletal/metabolism , Nova Scotia , Oxidative Stress/genetics , Perches/metabolism , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Water Pollutants, Chemical/metabolism
14.
Environ Toxicol Chem ; 36(4): 976-987, 2017 04.
Article in English | MEDLINE | ID: mdl-27595668

ABSTRACT

Kejimkujik National Park and National Historic Site, Nova Scotia, Canada, is considered a biological mercury (Hg) hotspot because the tissues of yellow perch (Perca flavescens) and common loons (Gavia immer) inhabiting the lakes frequently exceed so-called safe levels of Hg. In the present study, the relationships between Hg and overall health of males and females of 3 forage fish species (brown bullhead Ameirus nebulosus, banded killifish Fundulus diaphanus, and golden shiner Notemigonus crysoleucas; n = 6-18/sex/lake) in 6 lakes at the park were assessed using condition factor, liversomatic index (LSI), and macrophage aggregates (MAs; indicators of tissue damage). Mean muscle total Hg (THg) concentrations of brown bullhead, banded killifish, and golden shiner across lakes were 0.32 µg/g, 0.27 µg/g, and 0.34 µg/g, respectively. Condition was negatively related to muscle THg in golden shiner and banded killifish, LSI was not related to THg in any species, and all species showed evidence of increasing MA prevalence (counts and area) with increasing THg concentrations. The MAs were most prevalent in spleen tissues of golden shiner, with mean percentage cover ranging from 0.36% to 5.59% across lakes. In addition, the area of MAs appeared to be better predicted by THg concentration than was the number of MAs in the same tissue. These findings suggest that Hg is affecting the health of wild fishes in Kejimkujik National Park and National Historic Site and that other populations with similar or higher concentrations of this metal may also be at risk. Environ Toxicol Chem 2017;36:976-987. © 2016 SETAC.


Subject(s)
Fishes/metabolism , Macrophages/drug effects , Mercury/analysis , Methylmercury Compounds/analysis , Muscles/drug effects , Water Pollutants, Chemical/analysis , Animals , Cell Aggregation/drug effects , Environmental Monitoring/methods , Female , Fundulidae/metabolism , Ictaluridae/metabolism , Lakes/chemistry , Macrophages/pathology , Male , Muscles/chemistry , Nova Scotia , Organ Specificity
15.
Cell Stem Cell ; 4(6): 548-58, 2009 Jun 05.
Article in English | MEDLINE | ID: mdl-19497283

ABSTRACT

The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or overactivation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as compound RBPJ and Smo deficiency does not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression "signature." Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that Hh inhibition on leukemia-initiating cell maintenance can be targeted in future clinical trials.


Subject(s)
Hedgehog Proteins/physiology , Hematopoietic Stem Cells/physiology , Signal Transduction , Adult Stem Cells , Animals , Cell Differentiation , Gene Expression Profiling , Homeostasis , Leukemia , Mice , Mice, Inbred Strains , Receptors, G-Protein-Coupled/genetics , Receptors, Notch/metabolism , Smoothened Receptor
16.
Nat Immunol ; 7(4): 418-26, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16518394

ABSTRACT

Commitment of hematopoietic progenitors to the T cell lineage requires the integration of multiple signaling pathways. Evidence has suggested involvement of hedgehog (Hh) signaling in T cell differentiation through its signal transducer smoothened (Smo). However, the precise function of the Hh pathway remains controversial, mainly because T cell-specific in vivo genetic models have not been used. Using pre-T cell-specific, mature T cell-specific and poly(I).poly(C)-inducible deletions of Smo and antagonists of Smo signaling, we report here that Hh is an essential positive regulator of T cell progenitor differentiation. Furthermore, we localize Hh function to a stage preceding pre-T cell receptor signaling, connect Smo signaling to the activity of the Gli1 and Gli2 transcription factors and demonstrate that Hh affects regulators of thymocyte survival and proliferation.


Subject(s)
Hematopoietic Stem Cells/immunology , T-Lymphocytes/immunology , Thymus Gland/immunology , Trans-Activators/immunology , Animals , Cell Cycle/immunology , Cell Differentiation/immunology , DNA, Complementary/chemistry , DNA, Complementary/genetics , Hedgehog Proteins , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Polymerase Chain Reaction , Receptor, Notch1/immunology , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/immunology , Signal Transduction , Smoothened Receptor , Specific Pathogen-Free Organisms , T-Lymphocytes/cytology , T-Lymphocytes/metabolism , Thymus Gland/cytology , Thymus Gland/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Veratrum Alkaloids/pharmacology
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