Reciprocal inhibiting interactive mechanism between the estrogen receptor and aryl hydrocarbon receptor signaling pathways in goldfish (Carassius auratus) exposed to 17β-estradiol and benzo[a]pyrene

Yan, Zhenhua; Lu, Guanghua; He, Junjie

doi:10.1016/j.cbpc.2012.03.001

Cited by 16 publications

(8 citation statements)

References 65 publications

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“…These ubiquitous chemicals are found in complex mixtures and exert similar cross–talk inhibition of vitellogenin expression in a number of teleosts, including zebrafish, rainbow trout, sea bass, and goldfish (Anderson et al, 1996b; Vaccaro et al, 2005; Yan et al, 2012; Bugel et al, 2013). AHR cross–talk inhibition of normal estrogen receptor functions may occur through several distinct mechanisms, including (1) direct competition for xenobiotic response elements (EREs and DREs) in gene promoters, (2) squelching of common cofactors, (3), AHR-dependent induction of inhibitory factors (e.g.…”

Section: 0 Discussionmentioning

confidence: 99%

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

et al. 2014

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Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen–responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β–estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β–estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi–chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng/g 17β–estradiol, inhibition of gene induction ranged from 62% to 97% for all genes tested in the Newark Bay population, relative to induction levels in the reference population. The basis for this recalcitrant phenotype could not be explained by a change in 17β– estradiol metabolism, nuclear estrogen receptor expression, promoter methylation (gene silencing) or SNPs, all of which were unaltered and normal in the Newark Bay population. The decreased transcriptional sensitivity of estrogen–responsive genes is suggestive of a broad effect on estrogen receptor pathway signaling, and provides insight into the mechanisms of the endocrine disrupting effects in the Newark Bay population.

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Section: 0 Discussionmentioning

confidence: 99%

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

et al. 2014

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“…Residue levels of pesticides like endosulfan and chlorpyrifos have been reported in products from plants such as soya or maize [33] , [49] which are commonly used as ingredients in salmon feeds [4] . Both PAH and pesticides have been shown in several in vitro and in vivo experiments to cause lipid and endocrine disturbances and to induce cytochrome P450 enzymes in teleost fish [43] , [53] , [68] , [79] , [100] , [102] . PAHs are genotoxic [16] , [86] , [35] and exposure has been suggested to cause vitamin D signalling disruption [79] as well as an effect on cell membrane integrity [65] , [70] .…”

Section: Introductionmentioning

confidence: 99%

Omega-3 and alpha-tocopherol provide more protection against contaminants in novel feeds for Atlantic salmon ( Salmo salar L.) than omega-6 and gamma tocopherol

Søfteland¹,

Berntssen²,

Kirwan

et al. 2016

Toxicology Reports

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Extended use of plant ingredients in Atlantic salmon farming has increased the need for knowledge on the effects of new nutrients and contaminants in plant based feeds on fish health and nutrient-contaminant interactions. Primary Atlantic salmon hepatocytes were exposed to a mixture of PAHs and pesticides alone or in combination with the nutrients ARA, EPA, α-tocopherol, and γ-tocopherol according to a factorial design. Cells were screened for effects using xCELLigence cytotoxicity screening, NMR spectroscopy metabolomics, mass spectrometry lipidomics and RT-qPCR transcriptomics. The cytotoxicity results suggest that adverse effects of the contaminants can be counteracted by the nutrients. The lipidomics suggested effects on cell membrane stability and vitamin D metabolism after contaminant and fatty acid exposure. Co-exposure of the contaminants with EPA or α-tocopherol contributed to an antagonistic effect in exposed cells, with reduced effects on the VTG and FABP4 transcripts. ARA and γ-tocopherol strengthened the contaminant-induced response, ARA by contributing to an additive and synergistic induction of CYP1A, CYP3A and CPT2, and γ-tocopherol by synergistically increasing ACOX1. Individually EPA and α-tocopherol seemed more beneficial than ARA and γ-tocopherol in preventing the adverse effects induced by the contaminant mixture, though a combination of all nutrients showed the greatest ameliorating effect.

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“…The main toxicological effects of PAHs, however, are in their genotoxicity and potential endocrine disruption in teleosts (Donnelly and Naufal, 2010;van der Oost et al, 2003;Johnson et al, 2008). Suppressed steroid levels and steroid synthesis inhibition (Monteiro et al, 2000;Seruto et al, 2005;Yan et al, 2012) have been detected in PAH-exposed teleosts as well as retinoid signalling disruption (Benisek et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Toxicological effect of single contaminants and contaminant mixtures associated with plant ingredients in novel salmon feeds

Søfteland¹,

Kirwan

Hori

et al. 2014

Food and Chemical Toxicology

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Increasing use of plant feed ingredients may introduce contaminants not previously associated with farming of salmonids, such as pesticides and PAHs from environmental sources or from thermal processing of oil seeds. To screen for interaction effects of contaminants newly introduced in salmon feeds, Atlantic salmon primary hepatocytes were used. The xCELLigence cytotoxicity system was used to select optimal dosages of the PAHs benzo(a)pyrene and phenanthrene, the pesticides chlorpyrifos and endosulfan, and combinations of these. NMR and MS metabolic profiling and microarray transcriptomic profiling was used to identify novel biomarkers. Lipidomic and transcriptomic profiling suggested perturbation of lipid metabolism, as well as endocrine disruption. The pesticides gave the strongest responses, despite having less effect on cell viability than the PAHs. Only weak molecular responses were detected in PAH-exposed hepatocytes. Chlorpyrifos suppressed the synthesis of unsaturated fatty acids. Endosulfan affected steroid hormone synthesis, while benzo(a)pyrene disturbed vitamin D3 metabolism. The primary mixture effect was additive, although at high concentrations the pesticides acted in a synergistic fashion to decrease cell viability and down-regulate CYP3A and FABP4 transcription. This work highlights the usefulness of 'omics techniques and multivariate data analysis to investigate interactions within mixtures of contaminants with different modes of action.

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Reciprocal inhibiting interactive mechanism between the estrogen receptor and aryl hydrocarbon receptor signaling pathways in goldfish (Carassius auratus) exposed to 17β-estradiol and benzo[a]pyrene

Cited by 16 publications

References 65 publications

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

Omega-3 and alpha-tocopherol provide more protection against contaminants in novel feeds for Atlantic salmon ( Salmo salar L.) than omega-6 and gamma tocopherol

Toxicological effect of single contaminants and contaminant mixtures associated with plant ingredients in novel salmon feeds

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