I obtained my PhD in Physiology (Biology, UB, 2008) at the Institute of Marine Science, CMIMA-CSIC. The research undertaken during my doctoral studies determined the effects of temperature on fish sex differentiation. One of the main findings was that a temperature- induced epigenetic mechanism was responsible for the alterations of sexual differentiation in farmed fish. These results linked, for the first time, epigenetics to sex ratios shifts by temperature. I spent six months working at Cardiff University (UK), learning molecular biology techniques and deepening in the study of regulatory mechanisms of gene expression. In 2009, I joined the TEAMENDO research group at the Center for Advanced Research in Environmental Genomics at University of Ottawa (Canada). In collaboration with a multidisciplinary team, we examined the ecosystem-level effects of pesticide applications on experimental ponds. As a Postdoctoral Fellow, I was involved in the implementation, coordination and supervision of laboratory and field experiments, acquiring experience and knowledge in the area of Ecotoxicology. I joined the Environmental Toxicology group in 2014 at the Institute of Environmental Assessment and Water Research (IDAEA-CSIC), working in the characterization of new mechanisms of toxicity of emerging pollutants on zebrafish development. From this work, I published some papers as a senior author and consolidated my research line in aquatic toxicology. At present, I’m the coordinator of an Individual Fellow Marie Curie project that aims to characterize epigenetic signatures as biomarkers of ecotoxicological effects in fish. This new and independent research line combines my past experience on the epigenetic regulation of reproductive genes in fish and the knowledge of the molecular analysis of endocrine disruption.In the near future, I plan to study the complex effects that environmental pollutants have using novel approaches that include multi-omic studies and integrate research in environmental ecotoxico- epigenetics. I plan to conduct interdisciplinary research with a solid foundation and the talent to integrate different types of information that will also allow addressing the complexity of gene- environment interactions.
Abstract The genome revolution has radically changed our view of biological systems. The quantita... more Abstract The genome revolution has radically changed our view of biological systems. The quantitative determination of changes in all the major molecular components of the living cells, the “omics” approach, opened new fields for essentially all life sciences. Omic techniques generate huge datasets, usually at the high Gb/Tb level, that need to be decoded and interpreted to become understandable and manageable. Whereas multivariant data analyses are very efficient in reducing datasets to limited and workable sets of variables, the analysis of the biological results requires a biological interpretation, not only a statistical one. Ideally, the objective is to link omic data to specific, recognizable phenotypes causally related to the observed omic changes/variations (bottom-up approach), as well as to use them to identify the molecular events that triggered those changes (top-down approach). Fortunately, the existence of massive databases with omic information from thousands of previously published data facilitates to obtain this information, without which most of the omic data would be essentially useless. In this chapter, we explore the challenges, limitations, menaces, and future prospects of converting omic datasets in useful pieces of information, with special emphasis on environmental and human health risk assessment.
The spread of antibiotic resistance in bacteria is a matter of global concern, and the identifica... more The spread of antibiotic resistance in bacteria is a matter of global concern, and the identification of possible sources of the associated genetic elements (antibiotic resistance genes -ARGs-, components of the horizontal gene transfer mechanism), is becoming an urgent need. While the transmission of ARGs in medical settings have been adequately characterized, ARG propagation in agroecosystems remains insufficiently studied. Particularly crucial is the determination of potential risks associated to the use of swine slurries and related products as component of organic fertilizers, an increasingly used farming practice. We determined ARGs and antibiotic loads analyzed from swine slurries and digestates from eight farms from Catalonia (NE Spain), and compared the results with their microbiome composition. Both ARGs and antibiotic were conspicuous in farm organic wastes, and the levels of some antibiotics exceeded currently accepted minimum inhibitory concentrations. Particularly, the presence of high loads of fluoroquinolones was directly correlated to the prevalence of the related qnrS1 ARG in the slurry. We also found evidence that ARG loads were directly correlated to the prevalence of determined bacterial taxa (Actinobacteria, Proteobacteria, Spirochaeta), a parameter that could be potentially modulated by the processing of the raw slurry prior to their use as fertilizer.
The spread of antibiotic resistance genes (ARG) into agricultural soils, products, and foods seve... more The spread of antibiotic resistance genes (ARG) into agricultural soils, products, and foods severely limits the use of organic fertilizers in agriculture. In order to help designing agricultural practices that minimize the spread of ARG, we fertilized, sown, and harvested lettuces and radish plants in experimental land plots for two consecutive agricultural cycles using four types of fertilizers: mineral fertilization, sewage sludge, pig slurry, or composted organic fraction of municipal solid waste. The analysis of the relative abundances of more than 200,000 ASV (Amplicon Sequence Variants) identified a small, but significant overlap (<10%) between soil's and fertilizer microbiomes. Clinically relevant ARG were found in higher loads (up to 100 fold) in fertilized soils than in the initial soil, particularly in those treated with organic fertilizers, and their loads grossly correlated to the amount of antibiotic residues found in the corresponding fertilizer. Similarly, low, but measurable ARG loads were found in lettuce (tetM, sul1) and radish (sul1), corresponding the lowest values to samples collected from minerally fertilized fields. Comparison of soil samples collected along the total period of the experiment indicated a relatively year-round stability of soil microbiomes in amended soils, whereas ARG loads appeared as unstable and transient. The results indicate that ARG loads in soils and foodstuffs were likely linked to the contribution of bacteria from organic fertilizer to the soil microbiomes, suggesting that an adequate waste management and good pharmacological and veterinarian practices may significantly reduce the presence of these ARGs in agricultural soils and plant products.
Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) has been shown to act as an obesogen and t... more Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) has been shown to act as an obesogen and to disrupt lipid metabolism in zebrafish eleutheroembryos (ZE). To characterize the consequences of this disruption, we performed a detailed lipidomic study using ZE exposed to different BPA concentrations (0, 4, 6 and 8 mg/L of BPA) from day 2 to up to day 6 post fertilization (dpf). Total lipids at 4, 5 and 6 dpf were extracted by Folch method and analyzed by high-performance thin layer chromatography (HPTLC) as wide-range preliminary screening. Selected conditions (0 and 6 mg/L of BPA) were used to obtain a high-quality lipid profile using ultra high-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC-TOFMS). BPA exposed ZE exhibited increased amounts of triglycerides (TG), diglycerides (DG), phosphatidylcholines (PC) and phosphatidylinositols (PI), regarding the control group. Analysis of time- and BPA exposure-related patterns of specific lipid species showed a clear influence of unsaturation degree (mostly in DG and PC) and/or fatty acid chain length (mostly in TG and PC derivatives) on their response to the presence of BPA. A decreased yolk-sac and energy consumption in exposed individuals appeared as the main reason for the observed BPA-driven effects. Integration of these results with previous morphological, biochemical, transcriptomic, metabolomic and behavioral data suggests a disruption of different signalling pathways by BPA that starts at very low BPAconcentrations, whose effects propagate across different organization levels, and that cannot be only explained by the relatively weak estrogenic effect of BPA.
Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disrupto... more Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at t...
Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine... more Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach to study the effects of sub-lethal doses of these three EDCs on the metabolic profiles of zebrafish embryos exposed from 48 to 120hpf (hours post fertilization). Advanced chemometric data analysis methods were used to reveal effects on the subjacent regulatory pathways. EDC treatments induced changes in concentrations of about 50 metabolites for TBT and BPA, and of 25 metabolites for PFOS. The analysis of the corresponding metabolic changes suggested the presence of similar underlying zebrafish responses to BPA, TBT and PFOS affecting the metabolism of glycerophospholipids, amino acids, purines and 2-oxocarboxylic acids. We related the changes in glycerophospholipid meta...
Methods in molecular biology (Clifton, N.J.), 2018
The genome revolution represents a complete change on our view of biological systems. The quantit... more The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alteratio...
Amphibian tadpoles develop in aquatic environments where they are susceptible to the effects of p... more Amphibian tadpoles develop in aquatic environments where they are susceptible to the effects of pesticides and other environmental contaminants. Glyphosate-based herbicides are currently the most commonly used herbicide in the world and have been shown to affect survival and development of tadpoles under laboratory and mesocosm conditions. In the present study, whole wetland manipulations were used to determine if exposure to an agriculturally relevant application of Roundup WeatherMax(®), a herbicide formulation containing the potassium salt of glyphosate and an undisclosed surfactant, influences the development of wood frog tadpoles (Lithobates sylvaticus) under natural conditions. Wetlands were divided in half with an impermeable curtain so that each wetland contained a treatment and control side. Tadpoles were exposed to two pulses of this herbicide at an environmentally realistic concentration (ERC, 0.21 mg acid equivalent (a.e.)/L) and the predicted maximum environmental concentration (PMEC, 2.89 mg a.e./L), after which abundance, growth, development, and mRNA levels of genes involved in tadpole metamorphosis were measured. Results present little evidence that exposure to this herbicide affects abundance, growth and development of wood frog tadpoles. As part of the Long-term Experimental Wetlands Area (LEWA) project, this research demonstrates that typical agricultural use of Roundup WeatherMax(®) poses minimal risk to larval amphibian development. However, our gene expression data (mRNA levels) suggests that glyphosate-based herbicides have the potential to alter hormonal pathways during tadpole development.
In many cultured fish species, including the European sea bass, undesirable highly male-biased se... more In many cultured fish species, including the European sea bass, undesirable highly male-biased sex ratios are nevertheless frequent. High temperatures (∼21°C), typically used during the larval and early juvenile stages are thought to cause sex-reversal of genotypic females. Rearing at lower temperatures (&amp;amp;amp;amp;lt;17°C) has been investigated as a possible solution. However, besides reducing growth, they have sometimes resulted in equivocal
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, Jan 31, 2018
While the field of epigenetics is increasingly recognized to contribute to the emergence of pheno... more While the field of epigenetics is increasingly recognized to contribute to the emergence of phenotypes in mammalian research models across different developmental and generational timescales, the comparative biology of epigenetics in the large and physiologically diverse vertebrate infraclass of teleost fish remains comparatively understudied. The cypriniform zebrafish and the salmoniform rainbow trout and Atlantic salmon represent two especially important teleost orders, because they offer the unique possibility to comparatively investigate the role of epigenetic regulation in 3R and 4R duplicated genomes. In addition to their sequenced genomes, these teleost species are well-characterized model species for development and physiology, and therefore allow for an investigation of the role of epigenetic modifications in the emergence of physiological phenotypes during an organism's lifespan and in subsequent generations. This review aims firstly to describe the evolution of the re...
Environmental science and pollution research international, Jan 25, 2017
All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vita... more All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vitamin A that contribute to the normal vertebrate development by affecting gene expression through the retinoic acid signalling pathway. We show transcriptomic effects of the ectopic addition of atRA or 9cRA to zebrafish embryos at the posthatching embryonic stage. Exposure for 24 or 72 h to sublethal concentrations of both isomers resulted in characteristic transcriptome changes, in which many proliferation and development-related genes became underexpressed, whereas genes related to retinoid metabolism and some metabolic functions became overrepresented. While short and long exposures elicit essentially the same set of genes, atRA specifically induced expression of a specific subset of proteases, likely acting at the extracellular level, and of elements of the response to xenobiotics. These results reflect the well-known antiproliferative activity of retinoids, and they suggest a dysregul...
Environmental pollution (Barking, Essex : 1987), Jan 3, 2017
Although bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic conseq... more Although bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic consequences of its exposure are still poorly understood. In this study, we present a non-targeted LC-MS based metabolomic analysis in combination with a full-genome, high-throughput RNA sequencing (RNA-Seq) to reveal the metabolic effects and the subjacent regulatory pathways of exposing zebrafish embryos to BPA during the first 120 hours post-fertilization. We applied multivariate data analysis methods to extract biochemical information from the LC-MS and RNA-Seq complex datasets and to perform testable predictions of the phenotypic adverse effects. Metabolomic and transcriptomic data revealed a similar subset of altered pathways, despite the large difference in the number of identified biomarkers (around 50 metabolites and more than 1000 genes). These results suggest that even a moderate coverage of zebrafish metabolome may be representative of the global metabolic changes. These multi-omic...
Abstract The genome revolution has radically changed our view of biological systems. The quantita... more Abstract The genome revolution has radically changed our view of biological systems. The quantitative determination of changes in all the major molecular components of the living cells, the “omics” approach, opened new fields for essentially all life sciences. Omic techniques generate huge datasets, usually at the high Gb/Tb level, that need to be decoded and interpreted to become understandable and manageable. Whereas multivariant data analyses are very efficient in reducing datasets to limited and workable sets of variables, the analysis of the biological results requires a biological interpretation, not only a statistical one. Ideally, the objective is to link omic data to specific, recognizable phenotypes causally related to the observed omic changes/variations (bottom-up approach), as well as to use them to identify the molecular events that triggered those changes (top-down approach). Fortunately, the existence of massive databases with omic information from thousands of previously published data facilitates to obtain this information, without which most of the omic data would be essentially useless. In this chapter, we explore the challenges, limitations, menaces, and future prospects of converting omic datasets in useful pieces of information, with special emphasis on environmental and human health risk assessment.
The spread of antibiotic resistance in bacteria is a matter of global concern, and the identifica... more The spread of antibiotic resistance in bacteria is a matter of global concern, and the identification of possible sources of the associated genetic elements (antibiotic resistance genes -ARGs-, components of the horizontal gene transfer mechanism), is becoming an urgent need. While the transmission of ARGs in medical settings have been adequately characterized, ARG propagation in agroecosystems remains insufficiently studied. Particularly crucial is the determination of potential risks associated to the use of swine slurries and related products as component of organic fertilizers, an increasingly used farming practice. We determined ARGs and antibiotic loads analyzed from swine slurries and digestates from eight farms from Catalonia (NE Spain), and compared the results with their microbiome composition. Both ARGs and antibiotic were conspicuous in farm organic wastes, and the levels of some antibiotics exceeded currently accepted minimum inhibitory concentrations. Particularly, the presence of high loads of fluoroquinolones was directly correlated to the prevalence of the related qnrS1 ARG in the slurry. We also found evidence that ARG loads were directly correlated to the prevalence of determined bacterial taxa (Actinobacteria, Proteobacteria, Spirochaeta), a parameter that could be potentially modulated by the processing of the raw slurry prior to their use as fertilizer.
The spread of antibiotic resistance genes (ARG) into agricultural soils, products, and foods seve... more The spread of antibiotic resistance genes (ARG) into agricultural soils, products, and foods severely limits the use of organic fertilizers in agriculture. In order to help designing agricultural practices that minimize the spread of ARG, we fertilized, sown, and harvested lettuces and radish plants in experimental land plots for two consecutive agricultural cycles using four types of fertilizers: mineral fertilization, sewage sludge, pig slurry, or composted organic fraction of municipal solid waste. The analysis of the relative abundances of more than 200,000 ASV (Amplicon Sequence Variants) identified a small, but significant overlap (<10%) between soil's and fertilizer microbiomes. Clinically relevant ARG were found in higher loads (up to 100 fold) in fertilized soils than in the initial soil, particularly in those treated with organic fertilizers, and their loads grossly correlated to the amount of antibiotic residues found in the corresponding fertilizer. Similarly, low, but measurable ARG loads were found in lettuce (tetM, sul1) and radish (sul1), corresponding the lowest values to samples collected from minerally fertilized fields. Comparison of soil samples collected along the total period of the experiment indicated a relatively year-round stability of soil microbiomes in amended soils, whereas ARG loads appeared as unstable and transient. The results indicate that ARG loads in soils and foodstuffs were likely linked to the contribution of bacteria from organic fertilizer to the soil microbiomes, suggesting that an adequate waste management and good pharmacological and veterinarian practices may significantly reduce the presence of these ARGs in agricultural soils and plant products.
Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) has been shown to act as an obesogen and t... more Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) has been shown to act as an obesogen and to disrupt lipid metabolism in zebrafish eleutheroembryos (ZE). To characterize the consequences of this disruption, we performed a detailed lipidomic study using ZE exposed to different BPA concentrations (0, 4, 6 and 8 mg/L of BPA) from day 2 to up to day 6 post fertilization (dpf). Total lipids at 4, 5 and 6 dpf were extracted by Folch method and analyzed by high-performance thin layer chromatography (HPTLC) as wide-range preliminary screening. Selected conditions (0 and 6 mg/L of BPA) were used to obtain a high-quality lipid profile using ultra high-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC-TOFMS). BPA exposed ZE exhibited increased amounts of triglycerides (TG), diglycerides (DG), phosphatidylcholines (PC) and phosphatidylinositols (PI), regarding the control group. Analysis of time- and BPA exposure-related patterns of specific lipid species showed a clear influence of unsaturation degree (mostly in DG and PC) and/or fatty acid chain length (mostly in TG and PC derivatives) on their response to the presence of BPA. A decreased yolk-sac and energy consumption in exposed individuals appeared as the main reason for the observed BPA-driven effects. Integration of these results with previous morphological, biochemical, transcriptomic, metabolomic and behavioral data suggests a disruption of different signalling pathways by BPA that starts at very low BPAconcentrations, whose effects propagate across different organization levels, and that cannot be only explained by the relatively weak estrogenic effect of BPA.
Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disrupto... more Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at t...
Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine... more Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach to study the effects of sub-lethal doses of these three EDCs on the metabolic profiles of zebrafish embryos exposed from 48 to 120hpf (hours post fertilization). Advanced chemometric data analysis methods were used to reveal effects on the subjacent regulatory pathways. EDC treatments induced changes in concentrations of about 50 metabolites for TBT and BPA, and of 25 metabolites for PFOS. The analysis of the corresponding metabolic changes suggested the presence of similar underlying zebrafish responses to BPA, TBT and PFOS affecting the metabolism of glycerophospholipids, amino acids, purines and 2-oxocarboxylic acids. We related the changes in glycerophospholipid meta...
Methods in molecular biology (Clifton, N.J.), 2018
The genome revolution represents a complete change on our view of biological systems. The quantit... more The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alteratio...
Amphibian tadpoles develop in aquatic environments where they are susceptible to the effects of p... more Amphibian tadpoles develop in aquatic environments where they are susceptible to the effects of pesticides and other environmental contaminants. Glyphosate-based herbicides are currently the most commonly used herbicide in the world and have been shown to affect survival and development of tadpoles under laboratory and mesocosm conditions. In the present study, whole wetland manipulations were used to determine if exposure to an agriculturally relevant application of Roundup WeatherMax(®), a herbicide formulation containing the potassium salt of glyphosate and an undisclosed surfactant, influences the development of wood frog tadpoles (Lithobates sylvaticus) under natural conditions. Wetlands were divided in half with an impermeable curtain so that each wetland contained a treatment and control side. Tadpoles were exposed to two pulses of this herbicide at an environmentally realistic concentration (ERC, 0.21 mg acid equivalent (a.e.)/L) and the predicted maximum environmental concentration (PMEC, 2.89 mg a.e./L), after which abundance, growth, development, and mRNA levels of genes involved in tadpole metamorphosis were measured. Results present little evidence that exposure to this herbicide affects abundance, growth and development of wood frog tadpoles. As part of the Long-term Experimental Wetlands Area (LEWA) project, this research demonstrates that typical agricultural use of Roundup WeatherMax(®) poses minimal risk to larval amphibian development. However, our gene expression data (mRNA levels) suggests that glyphosate-based herbicides have the potential to alter hormonal pathways during tadpole development.
In many cultured fish species, including the European sea bass, undesirable highly male-biased se... more In many cultured fish species, including the European sea bass, undesirable highly male-biased sex ratios are nevertheless frequent. High temperatures (∼21°C), typically used during the larval and early juvenile stages are thought to cause sex-reversal of genotypic females. Rearing at lower temperatures (&amp;amp;amp;amp;lt;17°C) has been investigated as a possible solution. However, besides reducing growth, they have sometimes resulted in equivocal
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, Jan 31, 2018
While the field of epigenetics is increasingly recognized to contribute to the emergence of pheno... more While the field of epigenetics is increasingly recognized to contribute to the emergence of phenotypes in mammalian research models across different developmental and generational timescales, the comparative biology of epigenetics in the large and physiologically diverse vertebrate infraclass of teleost fish remains comparatively understudied. The cypriniform zebrafish and the salmoniform rainbow trout and Atlantic salmon represent two especially important teleost orders, because they offer the unique possibility to comparatively investigate the role of epigenetic regulation in 3R and 4R duplicated genomes. In addition to their sequenced genomes, these teleost species are well-characterized model species for development and physiology, and therefore allow for an investigation of the role of epigenetic modifications in the emergence of physiological phenotypes during an organism's lifespan and in subsequent generations. This review aims firstly to describe the evolution of the re...
Environmental science and pollution research international, Jan 25, 2017
All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vita... more All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vitamin A that contribute to the normal vertebrate development by affecting gene expression through the retinoic acid signalling pathway. We show transcriptomic effects of the ectopic addition of atRA or 9cRA to zebrafish embryos at the posthatching embryonic stage. Exposure for 24 or 72 h to sublethal concentrations of both isomers resulted in characteristic transcriptome changes, in which many proliferation and development-related genes became underexpressed, whereas genes related to retinoid metabolism and some metabolic functions became overrepresented. While short and long exposures elicit essentially the same set of genes, atRA specifically induced expression of a specific subset of proteases, likely acting at the extracellular level, and of elements of the response to xenobiotics. These results reflect the well-known antiproliferative activity of retinoids, and they suggest a dysregul...
Environmental pollution (Barking, Essex : 1987), Jan 3, 2017
Although bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic conseq... more Although bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic consequences of its exposure are still poorly understood. In this study, we present a non-targeted LC-MS based metabolomic analysis in combination with a full-genome, high-throughput RNA sequencing (RNA-Seq) to reveal the metabolic effects and the subjacent regulatory pathways of exposing zebrafish embryos to BPA during the first 120 hours post-fertilization. We applied multivariate data analysis methods to extract biochemical information from the LC-MS and RNA-Seq complex datasets and to perform testable predictions of the phenotypic adverse effects. Metabolomic and transcriptomic data revealed a similar subset of altered pathways, despite the large difference in the number of identified biomarkers (around 50 metabolites and more than 1000 genes). These results suggest that even a moderate coverage of zebrafish metabolome may be representative of the global metabolic changes. These multi-omic...
The genome revolution has brought about a complete change on our view of biological systems. The ... more The genome revolution has brought about a complete change on our view of biological systems. The quantitative determination of changes in all the major molecular components of the living cells, the "omics" approach, opened new fields for both health sciences and environmental toxicology. Endocrine disruption, i.e., the capacity of anthropogenic pollutants to alter the hormonal balance of the organisms, is one of the fields of Ecotoxicology in which omics has a relevant role. In the first place, the discovery of scores of potential targets in the genome of almost any Metazoan species studied so far, each of them being a putative candidate for interaction with endocrine disruptors. In addition, the understanding that ligands, receptors, and their physiological functions suffered fundamental variations during animal evolution makes it necessary to assess disruption effects separately for each major taxon. Fortunately, the same deal of knowledge on genes and genomes powered the development of new high-throughput techniques and holistic approaches. Genomics,
Teratogenicity Testing: Methods and Protocols, Methods in Molecular Biology, 2018
The genome revolution represents a complete change on our view of biological systems. The quantit... more The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the “omics” approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover, under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal welfare regulations) during the first 5 days after fertilization. Here we review the most important components of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could eventually lead to teratogenesis.
The genome revolution has radically changed our view of biological systems. The quantitative dete... more The genome revolution has radically changed our view of biological systems. The quantitative determination of changes in all the major molecular components of the living cells, the “omics” approach, opened new fields for essentially all life sciences. Omic techniques generate huge datasets, usually at the high Gb/Tb level, that need to be decoded and interpreted to become understandable and manageable. Whereas multivariant data analyses are very efficient in reducing datasets to limited and workable sets of variables, the analysis of the biological results requires a biological interpretation, not only a statistical one. Ideally, the objective is to link omic data to specific, recognizable phenotypes causally related to the observed omic changes/variations (bottom-up approach), as well as to use them to identify the molecular events that triggered those changes (top-down approach). Fortunately, the existence of massive databases with omic information from thousands of previously published data facilitates to obtain this information, without which most of the omic data would be essentially useless. In this chapter, we explore the challenges, limitations, menaces, and future prospects of converting omic datasets in useful pieces of information, with special emphasis on environmental and human health risk assessment.
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Papers by Laia Navarro-Martin
determination of changes in all major molecular components of the living cells, the “omics” approach,
opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics,
and others, together with appropriate prediction and modeling tools, will mark the future of developmental
toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology,
which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement.
Rodents and frogs have been the favorite models for studying human reproductive and developmental
disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a
major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system
to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover,
under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal
welfare regulations) during the first 5 days after fertilization. Here we review the most important
components
of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could
eventually lead to teratogenesis.