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Regulators and industry are actively seeking improvements and alternatives to current models and approaches to evaluate potential carcinogenicity of gene therapies (GTs). A meeting of invited experts was organized by NC3Rs/UKEMS (London, March 2023) to discuss this topic. This article describes the consensus reached among delegates on the definition of vector genotoxicity, sources of uncertainty, suitable toxicological endpoints for genotoxic assessment of GTs, and future research needs. The collected recommendations should inform the further development of regulatory guidelines for the nonclinical toxicological assessment of GT products.
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Terapia Genética , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Humanos , Fatores de Risco , Animais , Vetores Genéticos/efeitos adversos , Consenso , Neoplasias/terapia , Neoplasias/genética , Medição de RiscoRESUMO
This study presents the first comprehensive analysis of anthropogenic debris on the riverbanks of the Ciliwung River, covering upstream to downstream areas. The mean of debris found in each measurement was 32.79 ± 15.38 items/m2 with a weight of 106.00 ± 50.23 g/m2. Plastic debris accounted for over 50 % of all litter items identified and represents 55 % by weight, signifying a significantly high prevalence compared to global studies examining litter along riverbanks. The majority of the plastics found originated from Single-use applications and were predominantly made from Styrofoam. This investigation demonstrated the importance of actions to reduce single use applications and to improve waste management strategies. This can be achieved through proactive initiatives coupled with adaptable approaches, such as implementing effective urban planning and enhancing waste collection capacity.
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Despite their ban and restriction under the 2001 Stockholm Convention, persistent organic pollutants (POPs) are still widespread and pervasive in the environment. Releases of these toxic and bioaccumulative chemicals are ongoing, and their contribution to population declines of marine mammals is of global concern. To safeguard their survival, it is of paramount importance to understand the effectiveness of mitigation measures. Using one of the world's largest marine mammals strandings data sets, we combine published and unpublished data to examine pollutant concentrations in 11 species that stranded along the coast of Great Britain to quantify spatiotemporal trends over three decades and identify species and regions where pollutants pose the greatest threat. We find that although levels of pollutants have decreased overall, there is significant spatial and taxonomic heterogeneity such that pollutants remain a threat to biodiversity in several species and regions. Of individuals sampled within the most recent five years (2014-2018), 48% of individuals exhibited a concentration known to exceed toxic thresholds. Notably, pollutant concentrations are highest in long-lived, apex odontocetes (e.g., killer whales (Orcinus orca), bottlenose dolphins (Tursiops truncatus), and white-beaked dolphins (Lagenorhynchus albirostris)) and were significantly higher in animals that stranded on more industrialized coastlines. At the present concentrations, POPs are likely to be significantly impacting marine mammal health. We conclude that more effective international elimination and mitigation strategies are urgently needed to address this critical issue for the global ocean health.
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Golfinho Nariz-de-Garrafa , Caniformia , Poluentes Ambientais , Bifenilos Policlorados , Poluentes Químicos da Água , Orca , Animais , Poluentes Químicos da Água/toxicidade , Monitoramento AmbientalRESUMO
Endocrine disruption of wild fish, primarily resulting in the feminization of males, has been reported in English river sites for several decades. Estrogenic activity emanating from wastewater treatment works (WwTW) has been conclusively demonstrated to be the main driver of these feminized phenotypes. Here, we revisit 10 English river sites previously surveyed in the late 1990s and early 2000s to assess how the frequency and severity of feminization now compare with the historical surveys. In the contemporary assessment, 60% of the sites revisited still showed endocrine disruption at the tissue organization level (oocytes present in otherwise male gonads; intersex) and 90% of sites had average male plasma vitellogenin concentrations (female-specific yolk protein; a sensitive biomarker of estrogen exposure) above natural baseline levels. In contrast to the historic surveys, none of the males sampled in the contemporary survey had ovarian cavities. At one of the larger WwTW, improvements to treatment technology may have driven a significant reduction in intersex induction, whereas at several of the smaller WwTW sites, the frequencies of feminization did not differ from those observed in the late 1990s. In conclusion, we show that although the severity of feminization is now reduced at many of the revisited sites, endocrine-disrupting chemicals are still impacting wild fish living downstream of WwTW in England.
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Cyprinidae , Disruptores Endócrinos , Feminino , Masculino , Animais , Humanos , Feminização , Estrogênios , TestículoRESUMO
Experimental exposures aimed at assessing the risks posed by estrogens in waste-water treatment work (WwTW) effluents to fish populations have rarely considered whether populations differ in their sensitivity to estrogenic compounds. This is despite evidence that selection at genes involved in the estrogen response has occurred in wild populations, and evidence that genotype can influence estrogen-response. In this study we compare the effects of a two-year exposure to a low measured concentration (1.3 ng/L) of ethinylestradiol (EE2) on the sexual development of roach (Rutilus rutilus) whose parental generation was sampled from two river stretches heavily contaminated with WwTW effluent and from two without any known WwTW effluent contamination. Exposure to EE2 significantly reduced the proportion of genetic males and induced a range of feminized phenotypes in males. Significantly, exposure also increased the proportion of genetic females with vitellogenic oocytes from 51 to 96%, raising the possibility that estrogen pollution could impact populations of annually spawning fish species through advancing female reproduction by at least a year. However, there was no evidence that river origin affected sensitivity to estrogens in either sex. Thus, we conclude that chronic exposure to low level EE2 has reproductive health outcomes for both male and female roach, but we find no evidence that the nature or magnitude of the response is affected by the population origin.
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Cyprinidae , Poluentes Químicos da Água , Animais , Estrogênios/toxicidade , Etinilestradiol/toxicidade , Feminino , Masculino , Rios , Poluentes Químicos da Água/toxicidadeRESUMO
Lentiviral vectors (LV) are attractive for permanent and effective gene therapy. However, integration into the host genome can cause insertional mutagenesis highlighting the importance of understanding of LV integration. Insertion site (IS) tethering is believed to involve cellular proteins such as PSIP1/LEDGF/p75, which binds to the virus pre-integration complexes (PICs) helping to target the virus genome. Transcription factors (TF) that bind both the vector LTR and host genome are also suspected influential to this. To determine the role of TF in the tethering process, we mapped predicted transcription factor binding sites (pTFBS) near to IS chosen by HIV-1 LV using a narrow 20 bp window in infected human induced pluripotent stem cells (iPSCs) and their hepatocyte-like cell (HLC) derivatives. We then aligned the pTFBS with these sequences found in the LTRs of native and self-inactivated LTRs. We found significant enrichment of these sequences for pTFBS essential to HIV-1 life cycle and virus survival. These same sites also appear in HIV-1 patient IS and in mice infected with HIV-1 based LV. This in silco data analysis suggests pTFBS present in the virus LTR and IS sites selected by HIV-1 LV are important to virus survival and propagation.
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Infecções por HIV , HIV-1 , Células-Tronco Pluripotentes Induzidas , Humanos , Camundongos , Animais , Lentivirus/genética , HIV-1/genética , Integração Viral/genética , Fatores de Transcrição/genética , Sítios de LigaçãoRESUMO
Polychlorinated biphenyls (PCBs) are highly toxic and persistent aquatic pollutants that are known to bioaccumulate in a variety of marine mammals. They have been associated with reduced recruitment rates and population declines in multiple species. Evidence to date documents effects of PCB exposures on female reproduction, but few studies have investigated whether PCB exposure impacts male fertility. Using blubber tissue samples of 99 adult and 168 juvenile UK-stranded harbour porpoises (Phocoena phocoena) collected between 1991 and 2017, here we show that PCBs exposures are associated with reduced testes weights in adults with good body condition. In animals with poor body condition, however, the impact of PCBs on testes weights was reduced, conceivably due to testes weights being limited by nutritional stress. This is the first study to investigate the relationship between PCB contaminant burden and testes weights in cetaceans and represents a substantial advance in our understanding of the relationship between PCB exposures and male reproductive biology in cetaceans. As testes weight is a strong indicator of male fertility in seasonally breeding mammals, we suggest the inclusion of such effects in population level impact assessments involving PCB exposures. Given the re-emergent PCB threat our findings are globally significant, with potentially serious implications for long-lived mammals. We show that more effective PCB controls could have a substantial impact on the reproductive health of coastal cetacean species and that management actions may need to be escalated to ensure adequate protection of the most vulnerable cetacean populations.
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Phocoena , Bifenilos Policlorados , Toninhas , Testículo/efeitos dos fármacos , Poluentes Químicos da Água , Animais , Masculino , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Exposure of male fish to estrogenic substances from wastewater treatment works (WwTWs) results in feminization and reduced reproductive fitness. Nevertheless, self-sustaining populations of roach (Rutilus rutilus) inhabit river stretches polluted with estrogenic WwTW effluents. In this study, we examine whether such roach populations have evolved adaptations to tolerate estrogenic pollution by comparing frequency differences in single-nucleotide polymorphisms (SNPs) between populations sampled from rivers receiving either high- or low-level WwTW discharges. SNPs within 36 "candidate" genes, selected for their involvement in estrogenic responses, and 120 SNPs in reference genes were genotyped in 465 roaches. There was no evidence for selection in highly estrogen-dependent candidate genes, including those for the estrogen receptors, aromatases, and vitellogenins. The androgen receptor (ar) and cytochrome P450 1A genes were associated with large shifts in allele frequencies between catchments and in individual populations, but there is no clear link to estrogen pollution. Selection at ar in the effluent-dominated River Lee may have resulted from historical contamination with endocrine-disrupting pesticides. Critically, although our results suggest population-specific selection including at genes related to endocrine disruption, there was no strong evidence that the selection resulted from exposure to estrogen pollution.
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Cyprinidae , Poluentes Químicos da Água , Animais , Cyprinidae/genética , Estrogênios , Estrona , Humanos , Masculino , Rios , Vitelogeninas , Poluentes Químicos da Água/análiseRESUMO
Polychlorinated biphenyls (PCBs) are toxic, persistent, and lipophilic chemical compounds that accumulate to high levels in harbor porpoises (Phocoena phocoena) and other cetaceans. It is important to monitor PCBs in wildlife, particularly in highly exposed populations to understand if concentrations are declining and how levels relate to toxicological thresholds and indices of health like infectious disease mortality. Here we show, using generalized additive models and tissue samples of 814 U.K.-stranded harbor porpoises collected between 1990 and 2017, that mean blubber PCB concentrations have fallen below the proposed thresholds for toxic effects. However, we found they are still associated with increased rates of infectious disease mortality such that an increase in PCB blubber concentrations of 1 mg kg-1 lipid corresponds with a 5% increase in risk of infectious disease mortality. Moreover, rates of decline and levels varied geographically, and the overall rate of decline is slow in comparison to other pollutants. We believe this is evidence of long-term preservation in the population and continued environmental contamination from diffuse sources. Our findings have serious implications for the management of PCB contamination in the U.K. and reinforce the need to prevent PCBs entering the marine environment to ensure that levels continue to decline.
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Phocoena , Bifenilos Policlorados , Toninhas , Poluentes Químicos da Água , Tecido Adiposo , Animais , Animais SelvagensRESUMO
Polychlorinated biphenyls (PCBs) are a group of 209 persistent and bio-accumulative toxic pollutants present as complex mixtures in human and animal tissues. Harbor porpoises accumulate some of the highest levels of PCBs because they are long-lived mammals that feed at a high trophic level. Studies typically use the sum of a suite of individual chlorobiphenyl congeners (CBs) to investigate PCBs in wildlife. However, toxic effects and thresholds of CB congeners differ, therefore population health risks of exposure may be under or over-estimated dependent on the congener profiles present. In this study, we found congener profiles varied with age, sex and location, particularly between adult females and juveniles. We found that adult females had the highest proportions of octa-chlorinated congeners whilst juveniles had the highest proportions of tri- and tetra-chlorinated congeners. This is likely to be a consequence of pollutant offloading between mothers and calves during lactation. Analysis of the individual congener toxicities found that juveniles were exposed to a more neurotoxic CB mixture at a time when they were most vulnerable to its effects. These findings are an important contribution towards our understanding of variation in congener profiles and the potential effects and threats of PCB exposure in cetaceans.
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Phocoena , Animais , Animais Selvagens , Poluentes Ambientais , Feminino , Bifenilos Policlorados , Reino UnidoRESUMO
In vertebrates, the steroidogenesis enzyme 5α-reductase converts testosterone to the more potent androgen 5α-dihydrotestosterone. Homologues of 5α-reductase genes have been identified in molluscs. However, recent findings suggest that vertebrate-type steroid androgens are not utilised in molluscan reproductive development. Genomic searches have revealed that molluscs do not possess many of the steroidogenic enzymes required to make testosterone, nor a nuclear androgen receptor. Consequently, the role of 5α-reductase in molluscs presents a mystery. Here, developmental exposures of Biomphalaria glabrata to selective pharmaceutical 5α-reductase inhibitors elicited a strong, highly reproducible phenotypic response characterised by the development of elongated "banana-shaped" shell morphology. In comparison to untreated snails, the shells are open-coiled and the whorls are unattached. Dutasteride (5α-reductase inhibitor) is approximately 10-times more potent at provoking the banana-shaped shell phenotype than finasteride, paralleling the pharmaceuticals' efficacy in humans. Other enzyme inhibitors with different modes of action were tested to investigate the specificity of the phenotype. However, only the pharmaceutical 5α-reductase inhibitors provoked the response. Dutasteride elicited the same phenotype in a second gastropod, Physella acuta. In the absence of evidence for de novo androgen steroidogenesis in molluscs, these findings suggest that novel substrates for 5α-reductase exist in gastropods, lending support to the contention that molluscan endocrinology differs from the well-characterised vertebrate endocrine system.
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Inibidores de 5-alfa Redutase/farmacologia , Exoesqueleto/anatomia & histologia , Colestenona 5 alfa-Redutase/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Gastrópodes/anatomia & histologia , Gastrópodes/efeitos dos fármacos , Exoesqueleto/embriologia , Animais , Água Doce , Gastrópodes/embriologia , Gastrópodes/enzimologia , HumanosRESUMO
Endocrine disrupting chemicals (EDCs) are substances that alter the function of the endocrine system and consequently cause adverse effects to humans or wildlife. The release of particular EDCs into the environment has been shown to negatively affect certain wildlife populations and has led to restrictions on the use of some EDCs. Current chemical regulations aim to balance the industrial, agricultural and/or pharmaceutical benefits of using these substances with their demonstrated or potential harm to human health or the environment. A summary is provided of the natural science evidence base informing the regulation of chemicals released into the environment that may have endocrine disrupting effects on wildlife. This summary is in a format (a 'restatement') intended to be policy-neutral and accessible to informed, but not expert, policy-makers and stakeholders.
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Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Invertebrados/efeitos dos fármacos , Vertebrados , Animais , Animais Selvagens , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidadeRESUMO
The reproduction of vertebrates is regulated by endocrine and neuro-endocrine signaling molecules acting along the brain-pituitary-gonad (BPG) axis. The understanding of the neuroendocrine role played in reproductive function has been recently revolutionized since the KiSS1/GPR54 (KiSS1r) system was discovered in 2003 in human and mice. Kisspeptins, neuropeptides that are encoded by the KiSS genes, have been recognized as essential in the regulation of the gonadotropic axis. They have been shown to play key roles in puberty onset and reproduction by regulating the gonadotropin secretion in mammals while physiological roles in vertebrates are still poorly known. In order to provide new knowledge on basic reproductive physiology in fish as well as new tools to assess impacts of endocrine disrupting compounds (EDCs), the neurotransmitter system, i.e., gene/receptor, KISS/GPR54 might constitute an appropriate biomarker. This study provides new understandings on the neuroendocrine regulation of roach reproduction as well as new molecular tools to be used as biomarkers of endocrine disruption. This work completes the set of biomarkers already validated in this species.
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Cyprinidae/metabolismo , Disruptores Endócrinos/toxicidade , Kisspeptinas/metabolismo , Sistemas Neurossecretores/metabolismo , Receptores de Kisspeptina-1/genética , Reprodução/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Feminino , Kisspeptinas/genética , Masculino , Sistemas Neurossecretores/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Understanding the environmental factors driving species-genetic diversity correlations (SGDCs) is critical for designing appropriate conservation and management strategies to protect biodiversity. Yet, few studies have explored the impact of changing land use patterns on SGDCs specifically in aquatic communities. This study examined patterns of genetic diversity in roach (Rutilus rutilus L.) together with fish species composition across 19 locations in a large river catchment, spanning a gradient in land use. Our findings show significant correlations between some, but not all, species and genetic diversity end points. For example, genetic and species differentiation showed a weak but significant linear relationship across the Thames catchment, but additional diversity measures such as allelic richness and fish population abundance did not. Further examination of patterns in species and genetic diversity indicated that land use intensification has a modest effect on fish diversity compared to the combined influence of geographical isolation and land use intensification. These results indicate that environmental changes in riparian habitats have the potential to amplify shifts in the composition of stream fish communities in poorly connected river stretches. Conservation and management strategies for fish populations should, therefore, focus on enhancing connectivity between river stretches and limit conversion of nearby land to arable or urban use to maintain current levels of biodiversity.
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Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria.
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Ecotoxicologia/legislação & jurisprudência , Disruptores Endócrinos/toxicidade , Animais , União Europeia , Regulamentação Governamental , Humanos , Medição de Risco/legislação & jurisprudênciaRESUMO
Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters. Much of the estrogenic potency of wastewater treatment plant (WWTP) effluents can be attributed to the discharge of steroid estrogens including estradiol (E2), EE2 and E1 due to incomplete removal of these substances at the treatment plant. An evaluation of the efficacy of wastewater treatment processes requires the quantitative determination of individual substances most often undertaken using chemical analysis methods. Most frequently used methods include Gas Chromatography-Mass Spectrometry (GCMS/MS) or Liquid Chromatography-Mass Spectrometry (LCMS/MS) using multiple reaction monitoring (MRM). Although very useful for regulatory purposes, targeted chemical analysis can only provide data on the compounds (and specific metabolites) monitored. Ecotoxicology methods additionally ensure that any by-products produced or unknown estrogenic compounds present are also assessed via measurement of their biological activity. A number of in vitro bioassays including the Yeast Estrogen Screen (YES) are available to measure the estrogenic activity of wastewater samples. Chemical analysis in conjunction with in vivo and in vitro bioassays provides a useful toolbox for assessment of the efficacy and suitability of wastewater treatment processes with respect to estrogenic endocrine disrupting compounds. This paper utilizes a battery of chemical and ecotoxicology tests to assess conventional, advanced and emerging wastewater treatment processes in laboratory and field studies.
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Ecotoxicologia/métodos , Estrogênios/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , Cromatografia Líquida/métodos , Disruptores Endócrinos/análise , Disruptores Endócrinos/isolamento & purificação , Monitoramento Ambiental/métodos , Estrogênios/análise , Espectrometria de Massas/métodos , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. METHODS: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. RESULTS: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. CONCLUSIONS: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.
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Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Medição de Risco/métodos , Animais , Exposição Ambiental , Humanos , Modelos Teóricos , Testes de ToxicidadeRESUMO
Gastropod mollusks have been proposed as alternative models for male reproductive toxicity testing, due to similarities in their reproductive anatomy compared to mammals, together with evidence that endocrine disrupting chemicals can cause effects in some mollusks analogous to those seen in mammals. To test this hypothesis, we used the freshwater pulmonate snail, Biomphalaria glabrata, for which various genetic tools and a draft genome have recently become available, to investigate the effects of two steroid androgens on the development of mollusk secondary sexual organs. Here we present the results of exposures to two potent androgens, the vertebrate steroid; 5α-dihydrotestosterone (DHT) and the pharmaceutical anabolic steroid; 17α-methyltestosterone (MT), under continuous flow-through conditions throughout embryonic development and up to sexual maturity. Secondary sexual gland morphology, histopathology and differential gene expression analysis were used to determine whether steroid androgens stimulated or inhibited organ development. No significant differences between tissues from control and exposed snails were identified, suggesting that these androgens elicited no biologically detectable response normally associated with exposure to androgens in vertebrate model systems. Identifying no effect of androgens in this mollusk is significant, not only in the context of the suitability of mollusks as alternative model organisms for testing vertebrate androgen receptor agonists but also, if applicable to other similar mollusks, in terms of the likely impacts of androgens and anti-androgenic pollutants present in the aquatic environment.
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Androgênios/farmacologia , Biomphalaria/efeitos dos fármacos , Biomphalaria/fisiologia , Exposição Ambiental , Reprodução/efeitos dos fármacos , Androgênios/efeitos adversos , Animais , Di-Hidrotestosterona/farmacologia , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Metiltestosterona/farmacologiaRESUMO
Environmental estrogens originate from a variety of sources including sewage treatment plant (STP) effluents and adverse physiological effects (endocrine disruption) have been observed in several fish species sampled downstream of STP discharges. In this study we examined common carp (Cyprinus carpio) and roach (Rutilis rutilis) for signs of exposure to environmental estrogens in the iconic Yarra River, Melbourne, Australia. The Yarra River flows through the city of Melbourne and more than 2 million people live within the catchment. Two STPs discharge water into the Yarra River within the middle reaches, and the areas immediately downstream of these discharge locations were the focus of this study. Carp and roach were chosen as test species since both have been utilised extensively for endocrine disruption research throughout Europe, North America and Asia, and data from various international studies was used for comparison with the results of the present study. Neither species showed evidence of exposure to environmental estrogens, with no elevation of plasma vitellogenin levels in males and no incidence of intersex gonads. Most physiological endpoints in both species from this study were within ranges reported in carp and roach from reference sites in other studies, however some degenerative histological changes in both male and female gonads were observed. Surface water samples showed no estrogenic activity (measured by the yeast-estrogen screen, YES), but did display strong anti-estrogenic and weak androgenic activity (measured by the yeast-androgen screen, YAS). Whilst the results show no evidence of impacts from environmental estrogens in the Yarra River, the presence of both anti-estrogenic and androgenic activity in water samples, as well as some gonadal changes in carp is concerning and indicates that our focus needs to broaden, in order to look for biological impacts in resident fauna that might be due to environmental pollutants other than environmental estrogens.