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Toxicogenomics provides insights to toxicity pathways of neonicotinoids to aquatic insect, Chironomus dilutus
2020
Wei, Fenghua | Wang, Dali | Li, Huizhen | Xia, Pu | Ran, Yong | Yau, Ching
Neonicotinoid insecticides have posed a great threat to non-target organisms, yet the mechanisms underlying their toxicity are not well characterized. Major modes of action (MoAs) of imidacloprid were analyzed in an aquatic insect Chironomus dilutus. Lethal and sublethal outcomes were assessed in the midges after 96-h exposure to imidacloprid. Global transcriptomic profiles were determined using de novo RNA-sequencing to more holistically identify toxicity pathways. Transcriptional 10% biological potency values derived from ranked KEGG pathways and GO terms were 0.02 (0.01–0.08) (mean (95% confidence interval) and 0.05 (0.04–0.06) μg L⁻¹, respectively, which were more sensitive than those from phenotypic traits (10% lethal concentration: 0.44 (0.23–0.79) μg L⁻¹; 10% burrowing behavior concentration: 0.30 (0.22–0.43) μg L⁻¹). Major MoAs of imidacloprid in aquatic species were identified as follows: the activation of nicotinic acetylcholine receptors (nAChRs) induced by imidacloprid impaired organisms’ nerve system through calcium ion homeostasis imbalance and mitochondrial dysfunction, which posed oxidative stress and DNA damage and eventually caused death of organisms. The current investigation highlighted that imidacloprid affected C. dilutus at environmentally relevant concentrations, and elucidated toxicity pathways derived from gene alteration to individual outcomes, calling for more attention to toxicity of neonicotinoids to aquatic organisms.
Mostrar más [+] Menos [-]Tris(4-hydroxyphenyl)ethane (THPE), a trisphenol compound, is antiestrogenic and can retard uterine development in CD-1 mice
2020
Xiao, Han | Wang, Yue | Jia, Xiaojing | Yang, Lei | Wang, Xiaoning | Guo, Xuan | Zhang, Zhaobin
Tris (4-hydroxyphenyl)ethane (THPE), a trisphenol compound widely used as a branching agent and raw material in plastics, adhesives, and coatings is rarely regarded with concern. However, inspection of in vitro data suggests that THPE is an antagonist of estrogen receptors (ERs). Accordingly, we aimed to evaluate the antiestrogenicity of THPE in vivo and tested its effect via oral gavage on pubertal development in female CD-1 mice. Using uterotrophic assays, we found that THPE either singly, or combined with 17β-estradiol (E₂) (400 μg/kg bw/day) suppressed the uterine weights at low doses (0.1, 0.3, and 1 mg/kg bw/day) in 3-day treatment of weaning mice. When mice were treated with THPE during adolescence (for 10 days beginning on postnatal day 24), their uterine development was significantly retarded at doses of at least 0.1 mg/kg bw/day, manifest as decreased uterine weight, atrophic endometrial stromal cells and thinner columnar epithelial cells. Transcriptome analyses of uteri demonstrated that estrogen-responsive genes were significantly downregulated by THPE. Molecular docking shows that THPE fits well into the antagonist pocket of human ERα. These results indicate that THPE possesses strong antiestrogenicity in vivo and can disrupt normal female development in mice at very low dosages.
Mostrar más [+] Menos [-]Transcriptome analysis in Parhyale hawaiensis reveal sex-specific responses to AgNP and AgCl exposure
2020
Artal, Mariana Coletty | Pereira, Karina Danielle | Luchessi, Augusto Ducati | Okura, Vagner Katsumi | Henry, Theodore Burdick | Marques-Souza, Henrique | de Aragão Umbuzeiro, Gisela
Analysis of the transcriptome of organisms exposed to toxicants offers new insights for ecotoxicology, but further research is needed to enhance interpretation of results and effectively incorporate them into useful environmental risk assessments. Factors that must be clarified to improve use of transcriptomics include assessment of the effect of organism sex within the context of toxicant exposure. Amphipods are well recognized as model organisms for toxicity evaluation because of their sensitivity and amenability to laboratory conditions. To investigate whether response to metals in crustaceans differs according to sex we analyzed the amphipod Parhyale hawaiensis after exposure to AgCl and Ag nanoparticles (AgNP) via contaminated food. Gene specific analysis and whole genome transcriptional profile of male and female organisms were performed by both RT-qPCR and RNA-seq. We observed that expression of transcripts of genes glutathione transferase (GST) did not differ among AgCl and AgNP treatments. Significant differences between males and females were observed after exposure to AgCl and AgNP. Males presented twice the number of differentially expressed genes in comparison to females, and more differentially expressed were observed after exposure to AgNP than AgCl treatments in both sexes. The genes that had the greatest change in expression relative to control were those genes related to peptidase and catalytic activity and chitin and carbohydrate metabolic processes. Our study is the first to demonstrate sex specific differences in the transcriptomes of amphipods upon exposure to toxicants and emphasizes the importance of considering gender in ecotoxicology.
Mostrar más [+] Menos [-]The response of arsenic bioavailability and microbial community in paddy soil with the application of sulfur fertilizers
2020
Tang, Xianjin | Li, Luyao | Wu, Chuan | Khan, Muhammed Imran | Manzoor, Maria | Zou, Lina | Shi, Jiyan
Arsenic (As) has been recognized as one of the most toxic metalloids present in the surface soil contaminating food chain and posing threat to human life. Sulfur (S) fertilizer is often supplied in paddy soil for rice growth, but its impact on As mobility and related bacteria remains poorly understood. In this study, a pot experiment was set up with two different types of sulfur treatments (element sulfur and Na₂SO₄) to evaluate the effect of sulfur fertilizers on As speciation in porewater, As fractions in soil, As accumulation in rice plants. Besides, rhizosphere bacterial composition and functional genes that might influence As mobility were also studied. The results revealed that the addition of 150 mg/kg Na₂SO₄ decreased As(III) and As(V) concentrations in soil porewater at maturation stage by 77% and 64%, respectively. With the same sulfur content, Na₂SO₄ was more effective than element sulfur. The addition of sulfur fertilizers promoted rice growth and reduced As accumulation in shoots, further reduced As translocation from root to above-ground parts by 39–59%. The addition of sulfur fertilizers had little effect on genes involved in As metabolism. However, the relative abundance of Fe(III) and sulfate reduction related genera increased with the addition of 150 mg/kg Na₂SO₄, consistent with the increase of Fe(III) reducing bacteria Geobacteraceae and sulfate reducing gene dsrA. The phenomenon likely influenced the decrease of As concentrations in soil porewater and rice uptake. The outcomes indicate that promoting Fe- and S- reducing bacteria in the rhizosphere by sulfur fertilizers may be one way to reduce As risk in the soil-rice system.
Mostrar más [+] Menos [-]Evaluation of the effects of low concentrations of bisphenol AF on gonadal development using the Xenopus laevis model: A finding of testicular differentiation inhibition coupled with feminization
2020
Cai, Man | Li, Yuan-Yuan | Zhu, Min | Li, Jin-Bo | Qin, Zhan-Fen
Developmental exposures to estrogenic chemicals possibly cause structural and functional abnormalities of reproductive organs in vertebrates. Bisphenol AF (BPAF), a bisphenol A (BPA) analogue, has been shown to have higher estrogenic activity than BPA, but little is known about the effects of BPAF on gonadal development, particularly gonadal differentiation. We aimed to determine whether low concentrations of BPAF could disrupt gonadal differentiation and subsequent development using Xenopus laevis, a model species for studying feminizing effects of estrogenic chemicals. X. laevis tadpoles were exposed to BPAF (1, 10, 100 nM) or 17β-estradiol (E2, positive control) from stages 45/46 to 53 and 66 in a semi-static exposure system, with a prolonged treatment with the highest concentration to the eighth week post-metamorphosis (WPM8). Gonadal morphology and histology as well as sexually dimorphic gene expression were examined to evaluate the effects of BPAF. All concentrations of BPAF caused changes in testicular morphology at different developmental stages compared with controls. Specifically, at stage 53, BPAF like E2 resulted in decreases in both the size and the number of gonadal metameres (gonomeres) in testes, looking like ovaries. Some of BPAF-treated testes remained segmented and even became discontinuous and fragmented at subsequent stages. Histological abnormalities were also observed in BPAF-treated testes, such as ovarian cavity at stages 53 and 66 and poorly developed seminiferous tubules on WPM8. At the molecular level, BPAF inhibited expression of male highly expressed genes in testes at stage 53. Correspondingly, BPAF, like E2, inhibited cell proliferation in testes at stage 50. All results show that low concentrations of BPAF inhibited testicular differentiation and subsequent development in X. laevis, along with feminizing effects to some degree. Our finding implies a risk of BPAF to the male reproductive system of vertebrates including humans.
Mostrar más [+] Menos [-]β-catenin mediates fluoride-induced aberrant osteoblasts activity and osteogenesis
2020
Chu, Yanru | Gao, Yanhui | Yang, Yanmei | Liu, Yang | Guo, Zining | Wang, Limei | Huang, Wei | Wu, Liaowei | Sun, Dianjun | Gu, Weikuan
Excess fluoride in drinking water is an environmental issue of increasing worldwide concern, because of its adverse effect on human health. Skeletal fluorosis caused by chronic exposure to excessive fluoride is a metabolic bone disease characterized by accelerated bone turnover accompanied by aberrant activation of osteoblasts. It is not clear whether Wnt/β-catenin signaling, an important signaling pathway regulating the function of osteoblasts, mediates the pathogenesis of skeletal fluorosis. A cross-sectional case-control study was conducted in Tongyu County, Jilin Province, China showed that fluoride stimulated the levels of OCN and OPG, resulting in accelerated bone turnover in patients with skeletal fluorosis. To investigate the influence of fluoride on Wnt/β-catenin signaling pathway, 64 male BALB/c mice were allotted randomly to four groups and treated with deionized water containing 0, 55, 110 and 221 mg/L NaF for 3 months, respectively. The results demonstrated that fluoride significantly increased mouse cancellous bone formation and the protein expression of Wnt3a, phospho-GSK3β (ser 9) and Runx2. Moreover, partial correlation analysis indicated that there was no significant correlation between fluoride exposure and Runx2 protein levels, after adjusting for β-catenin, suggesting that β-catenin might play a crucial role in fluoride-induced aberrant osteogenesis. In vivo, viability of SaoS2 cells was significantly facilitated by 4 mg/L NaF, and fluoride could induce the abnormal activation of Wnt/β-catenin signaling, the expression of its target gene Runx2 and significantly increased Tcf/Lef reporter activity. Importantly, inhibition of β-catenin suppressed fluoride-induced Runx2 protein expression and the osteogenic phenotypes. Taken together, the present study provided in vivo and in vitro evidence reveals a potential mechanism for fluoride-induced aberrant osteoblast activation and indicates that β-catenin is the pivot molecule mediating viability and differentiation of osteoblasts and might be a therapeutic target for skeletal fluorosis.
Mostrar más [+] Menos [-]Effects of different mobile phone UMTS signals on DNA, apoptosis and oxidative stress in human lymphocytes
2020
Gulati, Sachin | Kosik, Pavol | Durdik, Matus | Skorvaga, Milan | Jakl, Lukas | Markova, Eva | Belyaev, Igor
Different scientific reports suggested link between exposure to radiofrequency radiation (RF) from mobile communications and induction of reactive oxygen species (ROS) and DNA damage while other studies have not found such a link. However, the available studies are not directly comparable because they were performed at different parameters of exposure, including carrier frequency of RF signal, which was shown to be a critical for appearance of the RF effects. For the first time, we comparatively analyzed genotoxic effects of UMTS signals at different frequency channels used by 3G mobile phones (1923, 1947.47, and 1977 MHz). Genotoxicity was examined in human lymphocytes exposed to RF for 1 h and 3 h using complimentary endpoints such as induction of ROS by imaging flow cytometry, DNA damage by alkaline comet assay, mutations in TP53 gene by RSM assay, preleukemic fusion genes (PFG) by RT-qPCR, and apoptosis by flow cytometry. No effects of RF exposure on ROS, apoptosis, PFG, and mutations in TP53 gene were revealed regardless the UMTS frequency while inhibition of a bulk RNA expression was found. On the other hand, we found relatively small but statistically significant induction of DNA damage in dependence on UMTS frequency channel with maximal effect at 1977.0 MHz. Our data support a notion that each specific signal used in mobile communication should be tested in specially designed experiments to rule out that prolonged exposure to RF from mobile communication would induce genotoxic effects and affect the health of human population.
Mostrar más [+] Menos [-]Toxic effects and mechanisms of three commonly used fungicides on the human colon adenocarcinoma cell line Caco-2
2020
Tao, Huaping | Bao, Zhiwei | Jin, Cuiyuan | Miao, Wenyu | Fu, Zhengwei | Jin, Yuanxiang
Fungicides, usually refer to the chemical agents that can effectively control or kill the pathogenic microorganisms. Here, we revealed the effects of three different fungicides, imazalil (IMZ), chlorothalonil (CTL) and carbendazim (CBZ), which are typical broad-spectrum fungicides that are detected at high levels in the natural environment, on heterogeneous human epithelial colorectal cells (Caco-2 cells). All three fungicides had the potential to induce different degrees of toxicity, cause apoptosis, reactive oxygen species (ROS) and even change the cell cycle in the cells. The half maximal inhibitory concentration (IC50) of CTL is the lowest among these three fungicides, suggesting that it may have the highest exposure risk, followed by IMZ, and CBZ. The results of the real-time PCR, Western blotting, and mitochondrial membrane potential (MMP) assays and the activities of key enzymes suggested that CTL induced apoptosis in Caco-2 cells via a mitochondrial-dependent pathway, as indicated by the upregulation of the expression of the apoptotic p53 and bax genes, the increase of the apoptosis marker cytochrome-c, the decrease of mRNA level of bcl-2 gene, and the decrease in the MMP. Exposure to two other fungicides also upregulated the transcriptional level of bax and the expression of cytochrome-c, but the mRNA level of bcl-2 was increased (IMZ) or unchanged (CBZ), suggesting that other pathways may be involved in the induction of cellular apoptosis by these two fungicides. In addition, all three of the fungicides could induce oxidative stress in Caco-2 cells. Our data showed that the three different kinds of fungicides all caused toxic effects in Caco-2 cells through various pathways.
Mostrar más [+] Menos [-]Time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens in response to elevated CO2
2020
Zhao, Mu-Hua | Zheng, Xiao-Xu | Liu, Jin-Ping | Zeng, Yun-Yun | Yang, Feng-Lian | Wu, Gang
To assess the time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens nymphs in response to elevated CO₂, we measured the time-dependent allocation of nutrient compositions and physiological metabolism in the bodies of N. lugens at 1h, 4h and 12h under elevated CO₂. Elevated CO₂ significantly increased the contents of nutrient compositions (protein, glucose and total amino acids) and catalase (CAT) enzyme activity in the body of N. lugens at 12h relative to 1h and 4h (P < 0.05). Significantly higher genes expression levels of acetylcholinesterase (AChE), heat shock protein (HSP70) and vitellogenin gene (vg) were observed in the body of N. lugens compared with those in ambient CO₂ at 4h (P < 0.05). These results showed that there was an instantaneous reaction of N. lugens nymphs to elevated CO₂, which indicated N. lugens may enhance stress defense response to future increasing CO₂ levels.
Mostrar más [+] Menos [-]Genome-wide DNA methylation analysis reveals significant impact of long-term ambient air pollution exposure on biological functions related to mitochondria and immune response
2020
Wang, Maiqiu | Zhao, Junsheng | Wang, Yan | Mao, Ying | Chao, Shin-Yi | Huang, Peng | Liu, Qiang | Ma, Yunlong | Yao, Yinghao | Yang, Zhongli | Yuan, Wenji | Cui, Wenyan | Payne, Thomas J. | Li, Ming D.
Exposure to long-term ambient air pollution is believed to have adverse effects on human health. However, the mechanisms underlying these impacts are poorly understood. DNA methylation, a crucial epigenetic modification, is susceptible to environmental factors and likely involved in these processes. We conducted a whole-genome bisulfite sequencing study on 120 participants from a highly polluted region (HPR) and a less polluted region (LPR) in China, where the HPR had much higher concentrations of five air pollutants (PM₂.₅, PM₁₀, SO₂, NO₂, and CO) (fold difference 1.6 to 6.6 times; P value 1.80E-07 to 3.19E-23). Genome-wide methylation analysis revealed 371 DMRs in subjects from the two areas and these DMRs were located primarily in gene regulatory elements such as promoters and enhancers. Gene enrichment analysis showed that DMR-related genes were significantly enriched in diseases related to pulmonary disorders and cancers and in biological processes related to mitochondrial assembly and cytokine production. Further, HPR participants showed a higher mtDNA copy number. Of those identified DMRs, 15 were significantly correlated with mtDNA copy number. Finally, cytokine assay indicated that an increased plasma interleukin-5 level was associated with greater air pollution. Taken together, our findings suggest that exposure to long-term ambient air pollution can lead to alterations in DNA methylation whose functions relate to mitochondria and immune responses.
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