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Cytochrome P450 1A transcript is a suitable biomarker of both exposure and response to diluted bitumen in developing frog embryos
2019
Lara-Jacobo, Linda R. | Willard, Brianna | Wallace, Sarah J. | Langlois, Valerie S.
In order for Alberta's thick bitumen to be transported through pipelines, condensates are added creating a diluted bitumen (dilbit) mixture. Recent pipeline expansion projects have generated concern about potential dilbit spills on aquatic wildlife health. Studies have suggested that polycyclic aromatic compounds (PACs) are toxic to aquatic vertebrates and could potentially also interfere with their endocrine system. The research objectives of this study were to investigate the toxicity of dilbit to developing frog embryos and to identify the molecular mechanisms of action involved. Fertilized embryos of Western clawed frog (Silurana tropicalis) were exposed for 72 h to water accommodated fractions (WAF; 0.7–8.9 μg/L TPACs) and chemically-enhanced WAFs (CEWAF; 0.09–56.7 μg/L TPACs) of Access Western Blend (AWB) and Cold Lake Blend (CLB) dilbits. Both dilbit's CEWAFs significantly increased embryonic mortality and malformation incidence in the highest treatments tested, while WAF treatments led to no visible toxic effects. Increases of the cytochrome P450 1A (cyp1a) mRNA levels were observed for all WAF and CEWAF dilbit treatments suggesting that phase I detoxification is activated in the dilbit-exposed larvae. When exposed to PAC concentrations ranging from 0.09 to 8.9 μg/L, the frogs displayed no observable malformations, but expressed significant increases of cyp1a mRNA levels (2- to 25-fold; indicating a suitable biomarker of exposure); however, when concentrations were of 46.6 μg/L or higher, both malformed frog phenotype and induction of cyp1a mRNA level (>250-fold) were measured (indicating a suitable biomarker of response). The expression of several genes related to cellular detoxification and endocrine disruption were also measured, but were not significantly altered by the treatments. In sum, cyp1a mRNA level is a highly sensitive endpoint to measure subtle molecular changes induced by PAC exposure in the frog embryos and larvae, and data suggest that PAC concentration higher than 46 μg/L would be toxic to the developing S. tropicalis.
اظهر المزيد [+] اقل [-]Genes associated with Parkinson's disease respond to increasing polychlorinated biphenyl levels in the blood of healthy females
2019
Bohler, Sacha | Krauskopf, Julian | Espín-Pérez, Almudena | Gebel, Stephan | Palli, Domenico | Rantakokko, Panu | Kiviranta, Hannu | Kyrtopoulos, Soterios A. | Balling, Rudi | Kleinjans, Jos
Polychlorinated biphenyls (PCBs) are a class of widespread environmental pollutants, commonly found in human blood, that have been suggested to be linked to the occurrence of sporadic Parkinson's disease (PD). It has been reported that some non-coplanar PCBs accumulate in the brains of female PD patients. To improve our understanding of the association between PCB exposure and PD risk we have applied whole transcriptome gene expression analysis in blood cells from 594 PCB-exposed subjects (369 female, 225 male).Interestingly, we observe that in females, blood levels of non-coplanar PCBs appear to be associated with expression levels of PD-specific genes. However, no such association was detected in males. Among the 131 PD-specific genes affected, 39 have been shown to display similar changes in expression levels in the substantia nigra of deceased PD patients. Especially among the down-regulated genes, transcripts of genes involved in neurotransmitter vesicle-related functions were predominant.
اظهر المزيد [+] اقل [-]Atrazine induced transgenerational reproductive effects in medaka (Oryzias latipes)
2019
Cleary, Jacob A. | Tillitt, Donald E. | Vom Saal, Frederick S. | Nicks, Diane K. | Claunch, Rachel A. | Bhandari, Ramji K.
Atrazine is presently one of the most abundantly used herbicides in the United States, and a common contaminant of natural water bodies and drinking waters in high-use areas. Dysregulation of reproductive processes has been demonstrated in atrazine exposed fish, including alteration of key endocrine pathways on hypothalamic-pituitary-gonadal (HPG) axis. However, the potential for atrazine-induced transgenerational inheritance of reproductive effects in fish has not been investigated. The present study examined the effects of early developmental atrazine exposure on transgenerational reproductive dysregulation in Japanese medaka (Oryzias latipes). F0 medaka were exposed to atrazine (ATZ, 5 or 50 μg/L), 17α-ethinylestradiol (EE2, 0.002 or 0.05 μg/L), or solvent control during the first twelve days of development with no subsequent exposure over three generations. This exposure overlapped with the critical developmental window for embryonic germ cell development, gonadogenesis, and sex determination. Exposed males and females of the F0 generation were bred to produce an F1 generation, and this was continued until the F2 generation. Sperm count and motility were not affected in F0 males; however, both parameters were significantly reduced in the males from F2 Low EE2 (0.002 μg/L), Low ATZ (5 μg/L), and High ATZ (50 μg/L) lineages. Fecundity was unaffected by atrazine or EE2 in F0 through F2 generations; however, fertilization rate was decreased in low atrazine and EE2 exposure lineages in the F2 generation. There were significant transgenerational differences in expression of the genes involved in steroidogenesis and DNA methylation. These results suggest that although early life exposure to atrazine did not cause significant phenotypes in the directly exposed F0 generation, subsequent generations of fish were at greater risk of reproductive dysfunction.
اظهر المزيد [+] اقل [-]TAK1 knock-down in macrophage alleviate lung inflammation induced by black carbon and aged black carbon
2019
Cheng, Zhiyuan | Chu, Hongqian | Wang, Siqi | Huang, Yao | Hou, Xiaohong | Zhang, Qi | Zhou, Wenjuan | Jia, Lixia | Meng, Qinghe | Shang, Lanqin | Song, Yiming | Hao, Weidong | Wei, Xuetao
Black carbon (BC) can combine with organic matter and form secondary pollutants known as aged BC. BC and aged BC can cause respiratory system inflammation and induce lesions at relevant sites, but the underlying mechanism has remained unknown. To gain insight into the potential mechanisms, we focused on macrophages and transforming growth factor β-activated kinase 1 (TAK1) which are a crucial factor in inflammation. Our research aims to determine the role of TAK1 in macrophages in pulmonary inflammation induced by particulate matter. In this study, BC and 1,4-naphthoquinone were mixed to model aged BC (1,4NQ-BC) in atmosphere. BC induced mice lung inflammation model, lung macrophage knock-down TAK1 animal model and primary macrophage knock-down TAK1 model were used to explore whether TAK1 in macrophage is a critical role in the process of inflammation. The results showed that the expressions of inflammatory cytokines (IL-1β, IL-6, IL-33) mRNA were significantly increased and the phosphorylation of MAPK and NF-κB signaling pathway related proteins were enhanced in RAW 264.7 cell lines. In vivo studies revealed that the indicators of pulmonary inflammation (pathology, inflammatory cell numbers) and related cytokines (IL-1β, IL-6, IL-33) mRNA expressions in CD11c-Map3k7⁻/⁻ animals were significantly lower than wild-type animals after mice were instilled particles. In mice primary macrophages, the expressions of IL-6, IL-33 mRNA were inhibited after TAK1 gene was knock-down. These results unequivocally demonstrated that TAK1 plays a crucial role in BC induced lung inflammation in mice, and we can infer that BC and 1,4NQ-BC cause these inflammatory responses by stimulating pulmonary macrophages.
اظهر المزيد [+] اقل [-]Molecular insights into ovary degeneration induced by environmental factors in female oriental river prawns Macrobrachium nipponense
2019
Fu, Chunpeng | Li, Fajun | Wang, Lifang | Li, Tingting
The oriental river prawn, Macrobrachium nipponense, is an important breeding species in China. The ovary development of this prawn is regulated by the genetic factors and external environmental factors and has obvious seasonal regularity. However, the molecular mechanism of regulating ovary degradation in M. nipponense remains unclear. To address this issue, we performed transcriptome sequencing and gene expression analyses of eyestalks, cerebral ganglia (CG) and thoracic ganglia (TG) of female M. nipponense between the full ovary stage and degenerate ovary stage. Differentially expressed genes enrichment analysis results identified several important pathways such as “phototransduction-fly,” “circadian rhythm-fly” and “steroid hormone biosynthesis secretion.” In the period of ovarian degeneration, the expressions of Tim, Per2 and red pigment concentration hormone (RPCH) were significantly decreased in the eyestalk, CG and TG. And expression of 7 genes in the steroid synthesis pathway, including steryl-sulfatase, cytochrome P450 family 1 subfamily A polypeptide 1, estradiol 17β-dehydrogenase 2, glucuronosyltransferase, 3-oxo-5-alpha-steroid 4-dehydrogenase 1, estradiol 17-dehydrogenase 1 and estrone sulfotransferase was significantly decreased in the CG. Food and light signals affect the expression of clock genes and thereby decrease the expression of RPCH and the estradiol synthesis-related genes in the nervous system, which may be the main cause of ovarian degeneration in M. nipponense. The results will contribute to a better understanding of the molecular mechanisms of ovarian development regulation in crustaceans.
اظهر المزيد [+] اقل [-]Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring
2019
Ren, Xin | Dai, Pengyuan | Perveen, Aneela | Tang, Qian | Zhao, Liangyu | Qingyangwanxi, | Li, Yansen | Li, Chunmei
Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARα, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes.
اظهر المزيد [+] اقل [-]Neurotoxicity of nonylphenol exposure on Caenorhabditis elegans induced by reactive oxidative species and disturbance synthesis of serotonin
2019
Cao, Xue | Wang, Xiaoli | Chen, Haibo | Li, Hui | T̤āriq, Muḥammad | Wang, Chen | Zhou, Yuanyuan | Liu, Yongdi
The present study was performed to evaluate the neurobehavioural deficit induced by nonylphenol (NP), a well-known xenobiotic chemical. The neurotoxic mechanism from oxidative stress and serotonin-related progress was also investigated. Caenorhabditis elegans was exposed at different levels of NP ranging from 0 to 200 μg L⁻¹ for 10 days. The results revealed that from a relatively low concentration (i.e., 10 μg L⁻¹), significant effects including decreased head thrashes, body bends and forging behaviour could be observed, along with impaired learning and memory behaviour plasticity. The level of reactive oxygen species (ROS) in head was significantly elevated with the increase of NP concentrations from 10 to 200 μg L⁻¹. Through antioxidant experiment, the oxidative damage caused by NP restored to some extent. At a NP concentration of 200 μg L⁻¹, the significant increased expression of stress-related genes, including sod-1, sod-3, ctl-2, ctl-3 and cyp-35A2 gene, was observed from integrated gene expression profiles. In addition, in comparison with wild-type N2 worms, the ROS accumulation was increased significantly with the mutation of sod-3. Tryptophan hydroxylase (TPH) in ADF and NSM neurons sharply decreased at the concentrations of 10–200 μg L⁻¹. The transcription of TPH synthesis-related genes and serotonin-related genes were both suppressed, including tph-1, cat-1, cat-4, ser-1, and mod-5. Overall, these results indicated that NP could induce neurotoxicity on Caenorhabditis elegans through excessive induction of ROS and disturbance synthesis of serotonin. The conducted research opened up new avenues for more effective exploration of neurotoxicity caused by NP.
اظهر المزيد [+] اقل [-]Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems
2019
Routti, Heli | Diot, Béatrice | Panti, Cristina | Duale, Nur | Fossi, Maria Cristina | Harju, Mikael | Kovacs, Kit M. | Lydersen, Christian | Scotter, Sophie E. | Villanger, Gro D. | Bourgeon, Sophie
Marine mammals in the Barents Sea region have among the highest levels of contaminants recorded in the Arctic and the Atlantic walrus (Odobenus rosmarus rosmarus) is one of the most contaminated species within this region. We therefore investigated the relationships bewteen blubber concentrations of lipophilic persistent organic pollutants (POPs) and plasma concentrations of perfluoroalkyl substances (PFASs) and markers of endocrine and immune functions in adult male Atlantic walruses (n = 38) from Svalbard, Norway. To do so, we assessed plasma concentrations of five forms of thyroid hormones and transcript levels of genes related to the endocrine and immune systems as endpoints; transcript levels of seven genes in blubber and 23 genes in blood cells were studied. Results indicated that plasma total thyroxine (TT4) concentrations and ratio of TT4 and reverse triiodothyronine decreased with increasing blubber concentrations of lipophilic POPs. Blood cell transcript levels of genes involved in the function of T and B cells (FC like receptors 2 and 5, cytotoxic T-lymphocyte associated protein 4 and protein tyrosine phosphatase non-receptor type 22) were increased with plasma PFAS concentrations. These results suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure.
اظهر المزيد [+] اقل [-]Multi-omics response of Pannonibacter phragmitetus BB to hexavalent chromium
2019
Chai, Liyuan | Ding, Chunlian | Li, Jiawei | Yang, Zhihui | Shi, Yan
The release of hexavalent chromium [Cr(VI)] into water bodies poses a major threat to the environment and human health. However, studies of the biological response to Cr(VI) are limited. In this study, a toxic bacterial mechanism of Cr(VI) was investigated using Pannonibacter phragmitetus BB (hereafter BB), which was isolated from chromate slag. The maximum Cr(VI) concentrations with respect to the resistance and reduction by BB are 4000 mg L−1 and 2500 mg L−1, respectively. In the BB genome, more genes responsible for Cr(VI) resistance and reduction are observed compared with other P. phragmitetus strains. A total of 361 proteins were upregulated to respond to Cr(VI) exposure, including enzymes for Cr(VI) uptake, intracellular reduction, ROS detoxification, DNA repair, and Cr(VI) efflux and proteins associated with novel mechanisms involving extracellular reduction mediated by electron transfer, quorum sensing, and chemotaxis. Based on metabolomic analysis, 174 metabolites were identified. Most of the upregulated metabolites are involved in amino acid, glucose, lipid, and energy metabolisms. The results show that Cr(VI) induces metabolite production, while metabolites promote Cr(VI) reduction. Overall, multi-enzyme expression and metabolite production by BB contribute to its high ability to resist/reduce Cr(VI). This study provides details supporting the theory of Cr(VI) reduction and a theoretical basis for the efficient bioremoval of Cr(VI) from the environment.
اظهر المزيد [+] اقل [-]Chronic exposure to dietary selenomethionine dysregulates the genes involved in serotonergic neurotransmission and alters social and antipredator behaviours in zebrafish (Danio rerio)
2019
Attaran, Anoosha | Salahinejad, Arash | Crane, Adam L. | Niyogi, Som | Chivers, Douglas P.
Selenium (Se) is a metalloid of potential interest from both a toxicological and nutritional perspective, having a range of safe intake. The adverse neuro-behavioural effects of Se have been investigated in both humans and fishes, but little is known about its effects on social behaviours or the serotonergic signaling pathway in the brain. In the present study, we investigated the effects of chorionic dietary exposure to Se (as selenomethionine) at different concentrations (control, 2.1, 11.6 or 31.5 μg/g dry wt.) on antipredator avoidance, shoaling behaviour, and social group preferences in adult zebrafish (Danio rerio). In addition, we also measured the expression of important genes in the serotonergic pathway that influence social behaviours. After 60 days of exposure, the highest dose (31.5 μg/g dry wt.) caused the highest level of baseline fear behaviour, with fish swimming lower in the water column and in tighter shoals compared to fish in the other treatments. With high levels of baseline fear, these fish did not significantly intensify fear behaviours in response to predation risk in the form of exposure to chemical alarm cues. When individual fish were given an opportunity to shoal with groups of differing sizes (3 vs. 4 individuals), fish exposed to the high dose spent less time with groups in general, and only control fish showed a significant preference for the larger group. In the zebrafish brain, we found significant upregulation in the mRNA expression of serotonin receptors (htr1aa and htr1b), a transporter (slc6a4a), and tryptophan hydroxylase-2 (tph2), whereas there was a downregulation of the monoamine oxidase (mao) gene. The results of this study suggest that disruption of serotonergic neurotransmission might have been responsible for Se-induced impairment of antipredator and social behaviour in zebrafish.
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