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Long-term toxicity of lindane through oxidative stress and cell apoptosis in Caenorhabditis elegans
2021
Yu, Yunjiang | Chen, Haibo | Hua, Xin | Wang, Zheng-Dong | Li, Liangzhong | Li, Zongrui | Xiang, Mingdeng | Ding, Ping
Lindane persists in the environment and bioaccumulates as an organochlorine pesticide and can pose risks to ecological environments and human health. To explore the long-term toxicity and underlying mechanisms of lindane, Caenorhabditis elegans was chosen as an animal model for toxicological study. The indicators of physiological, oxidative stress and cell apoptosis were examined in nematodes chronically exposed to environmentally relevant concentrations of lindane (0.01–100 ng/L). The data suggested that exposure to lindane at doses above 0.01 ng/L induced adverse physiological effects in C. elegans. Significant increases of ROS production and lipofuscin accumulation were observed in 100 ng/L of lindane-exposed nematodes, suggesting that lindane exposure induced oxidative stress in nematodes. Exposure to 10–100 ng/L of lindane also significantly increased the average number of germ cell corpses, which indicated cell apoptosis induced by lindane in C. elegans. Moreover, chronic exposure to 100 ng/L lindane significantly influenced the expression of genes related to oxidative stress and cell apoptosis (e.g., isp-1, sod-3, ced-3, and cep-1 genes). These results indicated that oxidative stress and cell apoptosis could play an important role in toxicity induced by lindane in nematodes.
Afficher plus [+] Moins [-]Effects of artificial light at night (ALAN) on gene expression of Aquatica ficta firefly larvae
2021
Chen, Yun-Ru | Wei, Wei-Lun | Tzeng, David T.W. | Owens, Avalon C.S. | Tang, Hsin-Chieh | Wu, Chia-Shong | Lin, Shih-Shun | Zhong, Silin | Yang, En-Cheng
Artificial light at night (ALAN) is a major driver of firefly population declines, but its physiological effects are not well understood. To investigate the impact of ALAN on firefly development, we exposed larval Aquatica ficta fireflies to ALAN for two weeks. High larval mortality was observed in the periods of 1–68 days and 106–134 days post-treatment, which may represent the short- and long-term impacts of ALAN. We then profiled the transcriptome of larval Aquatica ficta fireflies following two weeks of ALAN exposure. A total of 1262 (1.67% out of 75777 unigenes) were differentially expressed in the treatment group: 1157 were down-regulated, and 105 were up-regulated. Up-regulated unigenes were related to regulation of hormone levels, ecdysteroid metabolic process, and response to stimulus; down-regulated unigenes were related to negative regulation of insulin receptor signaling, germ cell development, oogenesis, spermatid development, and regulation of neuron differentiation. Transcriptome results suggest that the endocrine, reproductive, and neural development of firefly larvae could be impaired by even relatively brief period of ALAN exposure. This report contributes a much-needed molecular perspective to the growing body of research documenting the fitness impacts of ALAN on bioluminescent fireflies.
Afficher plus [+] Moins [-]Measuring mutagenicity in ecotoxicology: A case study of Cd exposure in Chironomus riparius
2021
Doria, Halina Binde | Waldvogel, Ann-Marie | Pfenninger, Markus
Existing mutagenicity tests for metazoans lack the direct observation of enhanced germline mutation rates after exposure to anthropogenic substances, therefore being inefficient. Cadmium (Cd) is a metal described as a mutagen in mammalian cells and listed as a group 1 carcinogenic and mutagenic substance. But Cd mutagenesis mechanism is not yet clear. Therefore, in the present study, we propose a method coupling short-term mutation accumulation (MA) lines with subsequent whole genome sequencing (WGS) and a dedicated data analysis pipeline to investigate if chronic Cd exposure on Chironomus riparius can alter the rate at which de novo point mutations appear. Results show that Cd exposure did not affect the basal germline mutation rate nor the mutational spectrum in C. riparius, thereby arguing that exposed organisms might experience a range of other toxic effects before any mutagenic effect may occur. We show that it is possible to establish a practical and easily implemented pipeline to rapidly detect germ cell mutagens in a metazoan test organism. Furthermore, our data implicate that it is questionable to transfer mutagenicity assessments based on in vitro methods to complex metazoans.
Afficher plus [+] Moins [-]2,2′,4,4′-tetrabromodiphenyl ether induces germ cell apoptosis through oxidative stress by a MAPK-mediated p53-independent pathway
2018
You, Xinyue | Xi, Jing | Liu, Weiying | Cao, Yiyi | Tang, Weifeng | Zhang, Xinyu | Yu, Yingxin | Luan, Yang
2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), a representative congener of polybrominated diphenyl ethers in the environment, is known to have reproductive toxicity. However, the underlying mechanisms remain to be clarified, especially in in vivo systems. In the present study, we employed Caenorhabditis elegans to study the effects of BDE-47 on reproduction. Our results showed that BDE-47 impaired worm fecundity and induced germ cell apoptosis. To elucidate the mechanisms, DNA damage and oxidative stress induction were investigated by determining the numbers of foci formation in transgenic worms expressing HUS-1::GFP and the levels of reactive oxygen species, respectively. We found that BDE-47 induced oxidative stress but not DNA damage, and treatment with the antioxidant, N-acetyl-L-cysteine, completely abrogated BDE-47-induced germ cell apoptosis. In addition, the apoptosis was blocked in mutants carrying mek-1, sek-1 or abl-1 loss-of-function alleles, but not in the p53/cep-1 deficient worms, suggesting that the mitogen-activated protein kinase (MAPK) signaling cascade was essential for BDE-47-induced germ cell apoptosis and p53/cep-1 was not required. Moreover, the apoptosis in the strains deficient for DNA damage response was not suppressed under BDE-47 treatment. Overall, we demonstrated that BDE-47 could induce oxidative stress and subsequent germ cell apoptosis in Caenorhabditis elegans through a MAPK-mediated p53-independent pathway.
Afficher plus [+] Moins [-]Triclosan (TCS) and triclocarban (TCC) induce systemic toxic effects in a model organism the nematode Caenorhabditis elegans
2017
Lenz, Katrina A. | Pattison, Claire | Ma, Hongbo
The broad application of triclosan (TCS) and triclocarban (TCC) as antimicrobials in household and personal care products has led to the concerns regarding their human health risk and environmental impact. Although many studies have examined the toxicological effects of these compounds to a wide range of aquatic organisms from algae to fish, their potential toxicity to an important model organism the nematode Caenorhabditis elegans has never been systematically investigated. Here we assessed the toxicological effects of TCS and TCC in C. elegans using endpoints from organismal to molecular levels, including lethality, reproduction, lifespan, hatching, germline toxicity, and oxidative stress. L4 stage or young adult worms were exposed to TCS or TCC and examined using above-mentioned endpoints. Both TCS and TCC showed acute toxicity to C. elegans, with 24-h LC50s of 3.65 (95% CI: 3.15, 4.3) mg/L and 0.91 (95% CI: 0.47, 1.53) mg/L, respectively. TCS at 0.1–2 mg/L and TCC at 0.01–0.5 mg/L, respectively, induced concentration dependent reduction in the worm's reproduction, lifespan, and delay in hatching. Using a DAF-16:GFP transgenic strain, we found both compounds induced oxidative stress in the worm, indicated by the relocalization of DAF-16:GFP from cytoplasm to the nucleus upon exposure. Germline toxicity of the two compounds was also demonstrated using a xol-1:GFP transgenic strain. These findings suggest that TCS and TCC induce systemic toxic effects in C. elegans. Further studies are needed to elucidate the potential mechanisms of toxicity of these antimicrobials in the model organism, especially their potential endocrine disruption effects.
Afficher plus [+] Moins [-]Radiocesium accumulation and germline mutations in chronically exposed wild boar from Fukushima, with radiation doses to human consumers of contaminated meat
2022
Anderson, Donovan | Kaneko, Shingo | Harshman, Amber | Okuda, Kei | Takagi, Toshihito | Chinn, Sarah | Beasley, James C. | Nanba, Kenji | Ishiniwa, Hiroko | Hinton, Thomas G.
Genetic effects and radioactive contamination of large mammals, including wild boar (Sus scrofa), have been studied in Japan because of dispersal of radionuclides from the Fukushima Dai-ichi Nuclear Power Plant in 2011. Such studies have generally demonstrated a declining trend in measured radiocesium body burdens in wildlife. Estimating radiation exposure to wildlife is important to understand possible long-term impacts. Here, radiation exposure was evaluated in 307 wild boar inhabiting radioactively contaminated areas (50–8000 kBq m⁻²) in Fukushima Prefecture from 2016 to 2019, and genetic markers were examined to assess possible germline mutations caused by chronic radiation exposures to several generations of wild boar. Internal Cs activity concentrations in boar remained high in areas near the power plant with the highest concentration of 54 kBq kg⁻¹ measured in 2019. Total dose rates to wild boar ranged from 0.02 to 36 μGy h⁻¹, which was primarily attributed to external radiation exposure, and dose rates to the maximally exposed animals were above the generic no-effects benchmark of 10 μGy h⁻¹. Using the estimated age of each animal, lifetime radiation doses ranged from <0.1 mGy to 700 mGy. Despite chronic exposures, the genetic analyses showed no significant accumulation of mutation events. Because wild boar is an occasional human dietary item in Japan, effective dose to humans from ingesting contaminated wild boar meat was calculated. Hypothetical consumption of contaminated wild boar meat from radioactively contaminated areas in Fukushima, at the per capita pork consumption rate (12.9 kg y⁻¹), would result in an average effective annual dose of 0.9 mSv y⁻¹, which is below the annual ingestion limit of 1 mSv y⁻¹. Additionally, a consumption rate of about 1.4 kg y⁻¹ of the most contaminated meat in this study would not exceed annual ingestion limits.
Afficher plus [+] Moins [-]Nanoplastic exposure in soil compromises the energy budget of the soil nematode C. elegans and decreases reproductive fitness
2022
Huang, Jiwei | Yen, Pei-Ling | Kuo, Yu-Hsuan | Chang, Chun-Han | Liao, Vivian Hsiu-Chuan
Environmental nanoplastics (NPs) can accumulate in soils, posing a potential risk to soil ecosystems. However, the ecotoxicity of NPs for soil organisms has received little research attention. This study investigated whether NP exposure in soil leads to reproductive decline in the soil nematode Caenorhabditis elegans and sought to determine the mechanisms by which it may occur. Wild-type N2 C. elegans L1 larvae were exposed to various concentrations of nano-sized polystyrene (100 nm) in soil (0, 1, 10, 100, and 1000 mg/kg dry weight) for 96 h. We show that nano-sized polystyrene (100 nm) labeled with red fluorescence significantly accumulated in the intestine of C. elegans in a dose-dependent fashion via soil exposure (8%–47% increase). In addition, NP soil exposure led to 7%–33% decline in the number of eggs in utero and 2.6%–4.4% decline in the egg hatching percentage. We also find that the number of germ cell corpses (31%–55% increase) and the mRNA levels of germline apoptosis marker gene ced-3 (14%–31% increase) were significantly higher with greater NP soil exposure (10, 100, and 1000 mg/kg), while intracellular ATP levels were significantly reduced. Finally, the DEBtox model, which is based on the dynamic energy budget theory, was applied to show that the increased reproductive costs for C. elegans caused by NPs in soil are associated with energy depletion and reproductive decline. The threshold value (4.18 × 10⁻⁶ mg/kg) for the energy budget also highlighted the potential high reproductive risk posed by NPs in terrestrial ecosystems. Our study provides new insights into how soil organisms interact with NPs in soil ecosystems.
Afficher plus [+] Moins [-]Airborne toluene exposure causes germline apoptosis and neuronal damage that promotes neurobehavioural changes in Caenorhabditis elegans
2020
Soares, Marcell Valandro | Charão, Mariele Feiffer | Jacques, Mauricio Tavares | dos Santos, Ana Laura Anibaletto | Luchese, Cristiane | Pinton, Simone | Ávila, Daiana Silva
Toluene is a highly volatile organic solvent present in gasoline. Exposure mainly occurs by absorption via the pulmonary tract and easily reaches the central nervous system, which causes toxic effects. Toluene toxicity has been described but not well established. The present work aimed to evaluate the effects of airborne exposure to toluene, the in vivo model Caenorhabditis elegans was assessed to determine whether nematode could be used to evaluate the effects of exposure to toluene and the possible mechanisms of toxicity of the solvent. Worms at the first or fourth larval stages were exposed to toluene for 48 or 24 h, respectively, in a laboratory-developed vapor chamber at concentrations of 450, 850, 1250 and 1800 ppm. We observed increases in worm mortality and significant developmental delays that occurred in a concentration-dependent manner. An increased incidence of apoptotic events in treated germline cells was shown, which was consistent with observed reductions in reproductive capacity. In addition, toluene promoted significant behavioural changes affecting swimming movements and radial locomotion, which were associated with changes in the fluorescence intensity and morphology of GABAergic and cholinergic neurons. We conclude that toluene exposure was toxic to C. elegans, with effects produced by the induction of apoptosis and neuronal damage.
Afficher plus [+] Moins [-]Endocrine disrupting effects of tebuconazole on different life stages of zebrafish (Danio rerio)
2019
Li, Shuying | Sun, Qianqian | Wu, Qiong | Gui, Wenjun | Zhu, Guonian | Schlenk, Daniel
Tebuconazole is a widely used fungicide that has been detected in water ecosystems, of which the concentrations may affect the endocrine function of aquatic organisms. At present study, tissue-specific bioaccumulation of tebuconazole was found in ovary of adult zebrafish, indicating a potential risk of endocrine disruption. In order to evaluate the potential endocrine disrupting effects, three life stages (2 hpf (hours post-fertilization) −60 dpf (days post-fertilization), Stage I; 60–120 dpf, Stage II; 180–208 dpf, Stage III) of zebrafish (Danio rerio) were chronically exposed to tebuconazole at the concentrations ranging from 0.05 mg/L to 1.84 mg/L. Result showed that exposed to tebuconazole could lead to a male-biased sex differentiation in juvenile zebrafish and significant decrease of the percentage of germ cells in sexually-mature zebrafish. Egg production was significantly inhibited by 57.8% and 19.2% after Stage II- and Stage III-exposures, respectively. The contents of 17β-estradiol in gonad decreased by 63.5% when exposed to 0.20 mg/L tebuconazole at Stage II and by 49.5% after exposed to 0.18 mg/L tebuconazole at Stage III, respectively. For all stages exposure, reductions in 17β-estradiol/testosterone ratio were observed, indicating an imbalance in steroids synthesis. Additionally, tebuconazole reduced the expression of cyp19a, which was consistent with the decrease of E2 level. In overall, the present findings indicated that, playing as an anti-estrogen-like chemical, tebuconazole inhibited the expression of Cyp19, thereby impairing steroid hormones biosynthesis, leading to a diminished fecundity of zebrafish.
Afficher plus [+] Moins [-]Exposures to chemical contaminants: What can we learn from reproduction and development endpoints in the amphibian toxicology literature?
2019
Slaby, Sylvain | Marin, Matthieu | Marchand, Guillaume | Lemiere, Sébastien
Environmental contamination is one of the major factors or cofactors affecting amphibian populations. Since 2000, the number of studies conducted in laboratory conditions to understand impacts of chemical exposures increased. They aimed to characterize biological effects on amphibians. This review proposes an overview of biological responses reported after exposures to metals, phytopharmaceuticals or emerging organic contaminants and focuses on endpoints relating to reproduction and development. Due to amphibian peculiar features, these periods of their life cycle are especially critical to pollutant exposures.Despite the large range of tested compounds, the same model species are often used as biological models and morphological alterations are the most studied observations. From the results, the laboratory-to-field extrapolation remained uneasy and exposure designs have to be more elaborated to be closer to environmental conditions. Few studies proposed such experimental approaches. Lastly, gametes, embryos and larvae constitute key stages of amphibian life cycle that can be harmed by exposures to freshwater pollutants. Specific efforts have to be intensified on the earliest stages and notably germ cells.
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