Illumina methylEPIC arrays on Peruvian individuals with high (>10 ppm) or low (<1 ppm) total hair mercury, a proxy for methylmercury exposure
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE207443 | GEO | 2022/10/06
REPOSITORIES: GEO
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Project description:Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated the direct exposure and transgenerational effects of MeHg, at tissue doses similar to those detected in exposed human populations, on sperm epimutations (i.e., differential DNA methylation regions [DMRs]) and neurobehavior (i.e., visual startle and spontaneous locomotion) in zebrafish, an established human health model. F1 generation embryos were exposed to MeHg (0, 1, 3, 10, 30, and 100 nM) for 24 hours ex vivo. F1 generation control and MeHg-exposed lineages were reared to adults and bred to yield the F2 generation, which was subsequently bred to the F3 generation. Direct exposure (F1 generation) and transgenerational actions (F3 generation) were then evaluated. Hyperactivity and visual deficit were observed in the unexposed descendants (F3 generation) of the MeHg-exposed lineage compared to control. An increase in F3 generation sperm epimutations was observed relative to the F1 generation. Investigation of the DMRs in the F3 generation MeHg-exposed lineage sperm revealed associated genes in the neuroactive ligand-receptor interaction and actin-cytoskeleton pathways being effected, which correlate to the observed neurobehavioral phenotypes. Developmental MeHg-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in F3 generation adult zebrafish. Therefore, mercury has the ability to promote the epigenetic transgenerational inheritance of disease in zebrafish, which significantly impacts its environmental health considerations in all species including humans.
2017-01-24 | GSE89144 | GEO
Project description:In order to investigate the underlying mechanisms of methylmecury (MeHg)-mediated toxicity to Atlantic cod (Gadus morhua), we analyzed the liver proteome of fish exposed in vivo to MeHg (0, 0.5, 2 mg/kg body weight) for 2 weeks. Label-free quantitative mass spectrometry enabled quantification of 1143 proteins, and 125 were differentially regulated between MeHg-treated samples and controls. Six proteins among the top differentially regulated (T23O, GLNA EPS8L2, APOA4, RAP1B, CZTZ) were analyzed using selected reaction monitoring (SRM). Supported by bioinformatics analyses, we conclude that MeHg disrupts mainly redox homeostasis and energy generating metabolic pathways in cod liver, the latter potentially modulated through MeHg-induced oxidative stress.
2016-08-09 | PXD004311 | Pride
Project description:Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge.
2016-12-29 | GSE87426 | GEO
Project description:New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC-PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain adequate levels of the beneficial fatty acids, eicosapentaenoic and docosahexaenoic (EPA and DHA, respectively). The present study investigated the use of an EPA+DHA oil derived from a transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar) containing low levels of fishmeal (35 %) and fish oil (10 %), reflecting current commercial formulations, to determine the impacts on intestinal transcriptome, tissue fatty acid profile and health of farmed salmon. Post-smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil (WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did not affect any of the fish performance or health parameters studied. Analyses of the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels comparable to those found twelve years ago.
2017-05-31 | E-MTAB-5529 | biostudies-arrayexpress
Project description:Three-month old zebrafish were fed Biodiet starter (4% body weight per day) with MeHg added at 0, 0.5, 5 and 50 ppm for six weeks. Atomic absorption spectrometry was applied to measure the level of MeHg in the whole fish body. Zebrafish at six weeks were sampled from each group for gene expression analysis by NimbleGen Gene Expression 12X135K zebrafish microarrays. MeHg-exposed trout and zebrafish did not show overt signs of toxicity, nor were significant differences seen in mortality, length, mass, or condition factor. The chronic accumulation of total Hg in zebrafish exhibited dose- and time-dependent patterns. The dysregulated genes in MeHg-treated fish have multiple functional annotations, such as involving metabolism, cellular development, ion binding, stress response, transcriptional regulation, and apoptotic pathways. These results show that numerous molecular pathways involved in the growth and development of multiple organ systems are disrupted by exposure to moderate levels of dietary MeHg. The dysregulated genes will be selected by further analysis and used as biomarkers for MeHg exposure in aquatic environments. This study will allow us to assess the potential impacts of low-level exposure to environmental MeHg in the food chain and on the health of humans and animals. Three-month old zebrafish (Danio rerio, average body 0.149 g) were fed Biodiet Starter (Bio-Oregon) 4% of body weight per day with MeHg added at 0ppm, 0.5ppm, 5ppm and 50ppm (with ethanol as vehicle). Fish at six weeks were sampled from each group for gene expression analysis. Three fish from each treatment group were used for microarray experiments. Total RNA from individual fish was isolated using Trizol reagent (Invitrogen) and further purified using the RNeasy MiniElute cleanup kit (Qiagen). Double-strand cDNA was synthesized from 10ug total RNA of individual fish by using Superscript Double-Stranded cDNA synthesis Kit (Invitrogen). ). One ug double strand DNA was labeled with Cy3 using One-Color DNA labeling Kit (NimbleGen), then hybridized to NimbleGen 12X135K array. The arrays were scanned at 2um on a NimbleGen MS200 scanner with auto-gain adjust. The TIFF images were gridded and extracted using NimbleScan v. 2.6. Expression data were normalized using the Robust Multichip Average (RMA) algorithm.
2013-06-01 | E-GEOD-32430 | biostudies-arrayexpress
Project description:The use of high levels of marine fish oil in aquafeeds is a non-sustainable practice. However, more sustainable oils sources from terrestrial plants do not contain long-chain polyunsaturated fatty acids (LC-PUFA). Consequently, feeds based on conventional vegetable oils reduce n-3 LC-PUFA levels in farmed fish. Therefore, the aquaculture industry desperately requires new, sustainable oil sources that contain high levels of n-3 LC-PUFA in order to supply the increasing demand for fish and seafood while maintaining the high nutritional quality of the farmed product. One approach to the renewable supply of n-3 LC-PUFA is metabolic engineering oilseed crops with the capacity to synthesize these essential fatty acids in seeds. In the present study, the oilseed Camelina sativa has been transformed with algal genes encoding the n-3 biosynthetic pathway and expression restricted to the seeds via seed-specific promoters to produce an oil containing > 20% eicosapentaenoic acid (EPA). This oil was investigated as a replacement for marine fish oil in feeds for post-smolt Atlantic salmon. In addition, this study with EPA-rich oil will contribute to our understanding of the biochemical and molecular mechanisms involved in the control and regulation of docosahexaenoic acid (DHA) production from EPA, and will thus better inform our understanding of this key part of the LC-PUFA biosynthetic pathway.
2015-12-21 | E-MTAB-2855 | biostudies-arrayexpress
Project description:N-3 long chain polyunsaturated fatty acids (n-3LC-PUFA) are essential components of vertebrate membrane lipids and are now at critically low levels in modern Western diets. The main human dietary source for n-3LC-PUFA is fish and seafood, and over 50% of global fish production is currently supplied by aquaculture. However, increasing pressure to include vegetable oils, which are devoid of n-3LC-PUFA, in aquaculture feeds reduces their content in farmed fish flesh. The aim of this investigation was to infer mechanisms determining flesh n-3LC-PUFA content in Atlantic salmon. The TRAITS / SGP Atlantic salmon 17k feature cDNA microarray (ArrayExpress accession: A-MEXP-1790) was used to compare hepatic mRNA expression in 8 families, reared under common conditions, which exhibited contrasting high and low flesh n-3LC-PUFA levels at harvest. The microarray interrogations incorporated a common pooled reference design, comprising a total of 16 hybridisations (8 families x 2 - dye swap). Each family sample comprised RNA pooled from six sibs.
2010-05-01 | E-TABM-955 | biostudies-arrayexpress
Project description:Novel DHA-enriched oils with high α-linolenic acid (ALA) content will be available in the near future as an alternative for dietary fish oil replacement in aquafeeds. As preliminary validation, we 1) assessed the ability of a diet containing a formulated oil blend (tuna oil + flaxseed oil, TOFX) with high DHA and ALA content to achieve fish oil-like omega-3 long-chain (≥C20) polyunsaturated fatty acids (n-3 LC-PUFA) tissue composition in Atlantic salmon smolts, and 2) applied liver proteomics as exploratory approach to understand the consequent nutritional changes. Comparisons were made on fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish tissue concentration of n-3 LC-PUFA and the n-3:n-6 ratio were significantly higher for TOFX than for FOPO, but not higher than for FO, while tissue retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an unexpected oxidative stress response as the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used blend oil.
2018-03-01 | PXD004114 | Pride
Project description:Three-month old zebrafish were fed Biodiet starter (4% body weight per day) with MeHg added at 0, 0.5, 5 and 50 ppm for six weeks. Atomic absorption spectrometry was applied to measure the level of MeHg in the whole fish body. Zebrafish at six weeks were sampled from each group for gene expression analysis by NimbleGen Gene Expression 12X135K zebrafish microarrays. MeHg-exposed trout and zebrafish did not show overt signs of toxicity, nor were significant differences seen in mortality, length, mass, or condition factor. The chronic accumulation of total Hg in zebrafish exhibited dose- and time-dependent patterns. The dysregulated genes in MeHg-treated fish have multiple functional annotations, such as involving metabolism, cellular development, ion binding, stress response, transcriptional regulation, and apoptotic pathways. These results show that numerous molecular pathways involved in the growth and development of multiple organ systems are disrupted by exposure to moderate levels of dietary MeHg. The dysregulated genes will be selected by further analysis and used as biomarkers for MeHg exposure in aquatic environments. This study will allow us to assess the potential impacts of low-level exposure to environmental MeHg in the food chain and on the health of humans and animals.
2013-06-01 | GSE32430 | GEO
Project description:Vegetable oils (VO) are possible substitutes for fish oil in aquafeeds but are limited by their lack of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). However, oilseed crops can be modified to produce n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, representing a potential option to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil with around 15 % total n-3 LC-PUFA to potentially substitute for fish oil in salmon feeds. Post-smolt Atlantic salmon (Salmo salar) were fed for 11-weeks with one of three experimental diets containing either fish oil (FO), wild-type Camelina oil (WCO) or transgenic Camelina oil (DCO) as added lipid source to evaluate fish performance, nutrient digestibility, tissue n-3 LC-PUFA, and metabolic impact determined by liver transcriptome analysis. The DCO diet did not affect any of the performance or health parameters studied and enhanced apparent digestibility of EPA and DHA compared to the WCO diet. The level of total n-3 LC-PUFA was higher in all the tissues of DCO-fed fish than in WCO-fed fish with levels in liver similar to those in fish fed FO. Endogenous LC-PUFA biosynthetic activity was observed in fish fed both the Camelina oil diets as indicated by the liver transcriptome and levels of intermediate metabolites such as docosapentaenoic acid, with data suggesting that the dietary combination of EPA and DHA inhibited desaturation and elongation activities. Expression of genes involved in phospholipid and triacylglycerol metabolism followed a similar pattern in fish fed DCO and WCO despite the difference in n-3 LC-PUFA contents.
2016-12-05 | E-MTAB-4621 | biostudies-arrayexpress