Gadolinium toxicity on sea urchin embryos of geographically and phylogenetically distant species

Pharmaceuticals are a class of emerging environmental contaminants. Gadolinium (Gd) is a metal of the lanthanide series of the elements whose chelates are commonly employed as contrast agents for magnetic resonance imaging, and subsequently released into the aquatic environment. We investigated the consequences of sea urchin embryo exposure to sublethal Gd concentrations, comparing the effects on the development of four phylogenetically and geographically distant species: two Mediterranean species, Paracentrotus lividus and Arbacia lixula, and two species living in the East coast of Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Measures of the Gd and Ca content inside e…

Toxicity of vanadium during development of sea urchin embryos: bioaccumulation, calcium depletion, ERK modulation and cell-selective apoptosis

Vanadium toxicology is a topic of considerable importance as this metal is widely used in industrial and biomedical fields. However, it represents a potential emerging environmental pollutant because wastewater treatment plants do not adequately remove metal compounds that are subsequently released into the environment. Vanadium applications are limited due to its toxicity, so it is urgent to define this aspect. This metal is associated with sea urchin embryo toxicity as it perturbs embryogenesis and skeletogenesis, triggering several stress responses. Here we investigated its bioaccumulation and the correlation with cellular and molecular developmental pathways. We used cytotoxic concentra…

Vanadium perturbs the fertilization outcome and the metalloproteinase activity in sea urchin embryos

Metal toxicology represents a current major topic due to the disper- sion of these elements in the environment. Metals are released from both natural sources and industrial activities. Some of them have also a clinical interest due to their application as metallodrugs (i.e., Pt, Cu, Au, Ru, and Y) or in medical diagnosis (Gd).1,2 Recently, V derivatives are considered as potential therapeutic factors in some diseases (e.g., obesity, diabetes, cancer, neurodegenerative and heart disorders). As a consequence, pharmaceutical residues could repre- sent emerging pollutants of aquatic environments, as wastewater treatment plants do not sufficiently remove these compounds3. Embryonic models repres…

The toxic effect of gadolinium ions on sea urchin embryos: comparison among phylogenetically distant species and focus on mechanisms regulating stress response and skeletogenesis.

Gadolinium (Gd) is a metal of the lanthanide series of the elements whose chelates are commonly employed as contrast agents for magnetic resonance imaging, and subsequently released into the aquatic environment. We investigated the consequences of sea urchin embryo exposure to sublethal Gd concentrations, comparing the effects on the development of four phylogenetically and geographically distant species: two Mediterranean species, Paracentrotus lividus and Arbacia lixula, and two species living in the East coast of Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Measures of the Gd content inside embryos by ICP-MS showed a time- and dose-dependent increase. In all these s…

Gadolinium-induced stress response causes a time-dependent miss-expression of regulative and structural genes involved in the development of the sea urchin P. lividus

Vanadium Toxicity Monitored by Fertilization Outcomes and Metal Related Proteolytic Activities in Paracentrotus lividus Embryos

Metal pharmaceutical residues often represent emerging toxic pollutants of the aquatic environment, as wastewater treatment plants do not sufficiently remove these compounds. Recently, vanadium (V) derivatives have been considered as potential therapeutic factors in several diseases, however, only limited information is available about their impact on aquatic environments. This study used sea urchin embryos (Paracentrotus lividus) to test V toxicity, as it is known they are sensitive to V doses from environmentally relevant to very cytotoxic levels (50 nM; 100 nM; 500 nM; 1 µM; 50 µM; 100 µM; 500 µM; and 1 mM). We used two approaches: The fertilization test (FT) and …

Effects of exposure to gadolinium on the development of geographically and phylogenetically distant sea urchins species.

Gadolinium (Gd), a metal of the lanthanide series used as contrast agent for magnetic resonance imaging, is released into the aquatic environment. We investigated the effects of Gd on the development of four sea urchin species: two from Europe, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Exposure to Gd from fertilization resulted in inhibition or alteration of skeleton growth in the plutei. The similar morphological response to Gd in the four species indicates a similar mechanism underlying abnormal skeletogenesis. Sensitivity to Gd greatly varied, with the EC50 ranging from 56 nM to 132 μM across the four species…

Sperm DNA fragmentation: An early and reliable marker of air pollution.

Environmental factors could have a key role in the continuous and remarkable decline of sperm quality observed in the last decades. This study compared the seminal parameters and sperm DFI in men living in areas with different levels of air pollution. Results demonstrate that both steel plants workers and patients living in a high polluted area show a mean percentage of sperm DNA fragmentation above 30%, highlighting a clear sperm damage. In this work, two different techniques were used to measure sperm DNA damage in patients’ groups, finding in both cases a high sperm DFI in patients living in polluted areas. We candidate sperm DNA fragmentation as a valuable early marker of the presence…

CELLULAR AND MOLECULAR MECHANISMS ACTIVATED IN SEA URCHIN EMBRYOS EXPOSED TO GADOLINIUM, EMERGING ENVIRONMENTAL CONTAMINANT

Toxic effects induced by vanadium on sea urchin embryos

Vanadium, a naturally occurring element widely distributed in soil, water and air, has received considerable interest because its compounds are often used in different applications, from industry to medicine. While the possible medical use of vanadium compounds is promising, its potential harmful effects on living organisms are still unclear. Here, for the first time, we provide a toxicological profile induced by vanadium on Paracentrotus lividus sea urchin embryos, reporting an integrated and comparative analysis of the detected effects reflecting vanadium-toxicity. At the morphological level we found a dose-dependent induction of altered phenotypes and of skeletal malformations. At the mo…

Asimmetric skeleton patterns induced by gadolinium ions in sea urchin embryos: focus on mechanisms regulating skeletogenesis and comparison among phylogenetically distant species

Autophagy is required for sea urchin oogenesis and early development.

SummaryAutophagy is a major intracellular pathway for the degradation and recycling of cytosolic components. Emerging evidence has demonstrated its crucial role during the embryo development of invertebrates and vertebrates. We recently demonstrated a massive activation of autophagy in Paracentrotus lividus embryos under cadmium stress conditions, and the existence of a temporal relationship between induced autophagy and apoptosis. Although there have been numerous studies on the role of autophagy in the development of different organisms, information on the autophagic process during oogenesis or at the start of development in marine invertebrates is very limited. Here we report our recent …

Gadolinium induces autophagy in sea urchin embryos

Interactive effects of increased temperature and gadolinium pollution in Paracentrotus lividus sea urchin embryos: a climate change perspective

Gradual ocean warming and marine heatwaves represent major threats for marine organisms already facing other anthropogenic-derived hazards, such as chemical contamination in coastal areas. In this study, the combined effects of thermal stress and exposure to gadolinium (Gd), a metal used as a contrasting agent in medical imaging which enters the aquatic environment, were investigated in the embryos and larvae of the sea urchin Paracentrotus lividus. Embryos were exposed to six treatments of three temperatures (18 °C, 21 °C, 24 °C) and two Gd concentrations (control: 0 μM; treated: 20 μM). With respect to developmental progression, increased temperature accelerated development and achievemen…

HUMAN SPERM CELL AS EARLY BIOINDICATOR OF MALE HEALTH AND REPRODUCTION

Environmental factors could have a key role in the remarkable and continuous decline of sperm quality observed in the last fifty years. This study addressed the gap of knowledge on the effect of air pollutants on sperm DNA fragmentation, comparing the seminal parameters from men living in locations with different levels of air pollution. The detrimental effects of environmental pollution in the Taranto area are alarming: the high level of pollutants released from the steel plants in the atmosphere can cause health and fertility issues. Our study analyzed sperm samples from three groups of patients: i) workers of Taranto steel plants; ii) Taranto residents; iii) Palermo residents, assumed as…

Gadolinium perturbs expression of skeletogenic genes, calcium uptake and larval development in phylogenetically distant sea urchin species

Chelates of Gadolinium (Gd), a lanthanide metal, are employed as contrast agents for magnetic resonance imaging and are released into the aquatic environment where they are an emerging contaminant. We studied the effects of environmentally relevant Gd concentrations on the development of two phylogenetically and geographically distant sea urchin species: the Mediterranean Paracentrotus lividus and the Australian Heliocidaris tuberculata. We found a general delay of embryo development at 24 h post-fertilization, and a strong inhibition of skeleton growth at 48 h. Total Gd and Ca content in the larvae showed a time- and concentration-dependent increase in Gd, in parallel with a reduction in C…

Regolazione genica e biomineralizzazione in embrioni di riccio di mare.

Gli echinodermi possiedono un esteso endoscheletro composto da calcite di magnesio, una forma di carbonato di calcio che contiene piccole quantità di carbonato di magnesio e di proteine occluse nella matrice [1]. Nell’ambito del progetto europeo del 7FP Biomintec 2008-2012 (http://www.biomintec.de/), focalizzato sui meccanismi molecolari che stanno alla base dei processi di biomineralizzazione e volto alla futura applicazione di nuovi biomateriali, abbiamo studiato gli effetti della deprivazione di magnesio sullo sviluppo dell’embrione di riccio di mare Arbacia lixula. Gli embrioni sono stati analizzati morfologicamente, valutando l’impatto sullo sviluppo a vari stadi (3, 6, 24, 48 e 72 ore…

Vanadium Modulates Proteolytic Activities and MMP-14-Like Levels during Paracentrotus lividus Embryogenesis

The increasing industrial use of vanadium (V), as well as its recent medical use in various pathologies has intensified its environmental release, making it an emerging pollutant. The sea urchin embryo has long been used to study the effects induced by metals, including V. In this study we used an integrated approach that correlates the biological effects on embryo development with proteolytic activities of gelatinases that could better reflect any metal-induced imbalances. V-exposure caused morphological/morphometric aberrations, mainly concerning the correct distribution of embryonic cells, the development of the skeleton, and the embryo volume. Moreover, V induced a concentration change …

The Role of Autophagy and Apoptosis During Embryo Development

Programmed cell death (PCD) and cell survival are two sides of the same coin. Autopha‐ gy and apoptosis are crucial processes during embryo development of Invertebrates and Vertebrates organisms, as they are necessary for the formation of a new organism, start‐ ing from a fertilized egg. Fertilization triggers cell remodeling from each gamete to a toti‐ potent zygote. During embryogenesis, the cells undergo various processes, thus allowing the transformation of the embryo into an adult organism. In particular, cells require the appropriate tools to suddenly modify their morphology and protein content in order to respond to intrinsic and external stimuli. Autophagy and apoptosis are involved…

Cadmium stress effects indicating marine pollution in different species of sea urchin employed as environmental bioindicators

In recent years, researches about the defense strategies induced by cadmium stress have greatly increased, invading several fields of scientific research. Mechanisms of cadmium-induced toxicity continue to be of interest for researchers given its ubiquitous nature and environmental distribution, where it often plays the role of pollutant for numerous organisms. The presence in the environment of this heavy metal has been constantly increasing because of its large employment in several industrial and agricultural activities. Cadmium does not have any biological role and, since it cannot be degraded by living organisms, it is irreversibly accumulated into cells, interacting with cellular comp…

Effects of magnesium deprivation on development and biomineralization in the sea urchin Arbacia lixula

Echinoderms have an extensive endoskeleton composed of magnesian calcite and occluded matrix proteins. As biomineralization in sea urchin larvae is sensitive to the Magnesium:Calcium ratio of seawater, we investigated the effects of magnesium deprivation on development and skeletogenesis in the sea urchin Arbacia lixula. We focused on the localization of the skeletogenic cells (primary mesenchyme cells) and the spatial expression of associated genes. Embryos reared in Mg-free seawater exhibited developmental delay from 6-h post-fertilization and at 24 h embryos showed complete lack of biomineral formation. Larvae (48–72 h) exhibited severe skeleton malformations. Fluorescent labelling revea…

Vanadium induces calcium depletion and cell selective apoptosis during development of sea urchin embryos

Vanadium (V) is a metal widely distributed in soil, water and air. It has recently received growing interest because its compounds are often used in different applications, from industry to medicine.1 Here, using atomic absorption spectrometry, we demonstrate the predisposition of V to accumulate directly into embryonic cells, interfering with Ca uptake. At the morphological level, we observed dose- and time-dependent effects on phenotypes and on skeletal malformations. At the molecular level, V-exposed embryos showed the activation of the cellular stress response, inducing Hsp 60 and Hsp 70 synthesis and the activation of autophagy and apoptosis. The Hsps-mediated stress response to V appe…

Autophagy induction in sea urchin embryos exposed to gadolinium ions

Sea urchin embryos are highly sensitive to several kinds of stressors, and able to activate different defense strategies. Gadolinium (Gd) is a metal of the lanthanide series of the elements: its chelates are employed as contrast agents for magnetic resonance imaging since the 1980s. Gd complexes are released in the aquatic environment, making Gd an emergent environmental pollutant. In this study we focused on the effects of Gd ions on sea urchin embryos development. The study was conducted looking at three different processes: general development, apoptosis and autophagy. At the whole morphological level, Paracentrotus lividus sea urchin embryos continuously exposed to Gd ions displayed mor…

Toxicological Impact of Rare Earth Elements (REEs) on the Reproduction and Development of Aquatic Organisms Using Sea Urchins as Biological Models

The growing presence of lanthanides in the environment has drawn the attention of the scientific community on their safety and toxicity. The sources of lanthanides in the environment include diagnostic medicine, electronic devices, permanent magnets, etc. Their exponential use and the poor management of waste disposal raise serious concerns about the quality and safety of the ecosystems at a global level. This review focused on the impact of lanthanides in marine organisms on reproductive fitness, fertilization and embryonic development, using the sea urchin as a biological model system. Scientific evidence shows that exposure to lanthanides triggers a wide variety of toxic insults, includi…

Autophagy as a defense strategy against stress: focus on Paracentrotus lividus sea urchin embryos exposed to cadmium

Autophagy is used by organisms as a defense strategy to face environmental stress. This mechanism has been described as one of the most important intracellular pathways responsible for the degradation and recycling of proteins and organelles. It can act as a cell survival mechanism if the cellular damage is not too extensive or as a cell death mechanism if the damage/stress is irreversible; in the latter case, it can operate as an independent pathway or together with the apoptotic one. In this review, we discuss the autophagic process activated in several aquatic organisms exposed to different types of environmental stressors, focusing on the sea urchin embryo, a suitable system recently in…

Induction of skeletal abnormalities and autophagy in Paracentrotus lividus sea urchin embryos exposed to gadolinium.

Abstract Gadolinium (Gd) concentration is constantly increasing in the aquatic environment, becoming an emergent environmental pollutant. We investigated the effects of Gd on Paracentrotus lividus sea urchin embryos, focusing on skeletogenesis and autophagy. We observed a delay of biomineral deposition at 24 hours post fertilization (hpf), and a strong impairment of skeleton growth at 48 hpf, frequently displayed by an asymmetrical pattern. Skeleton growth was found partially resumed in recovery experiments. The mesodermal cells designated to biomineralization were found correctly migrated at 24 hpf, but not at 48 hpf. Western blot analysis showed an increase of the LC3-II autophagic marker…

Toxicity induced by Gadolinium ions on sea urchin embryos: comparison among phylogenetically distant species and focus on stress response and skeletogenesis.

Pharmaceuticals are a class of emerging environmental contaminants. Gadolinium (Gd) is a lanthanide metal whose chelates are employed as contrast agents for magnetic resonance imaging, and subsequently released into the aquatic environment. We investigated the effects of exposure to sublethal Gd concentrations on the development of four phylogenetically and geographically distant sea urchin species: two Mediterranean, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Sensitivity to Gd greatly varied, with EC50 ranging from 56 nM to 132 µM across the four species. Measures of the Gd and Ca content inside embryos showed a…

Gene expression and stress response in sea urchin embryos with skeleton defects caused by magnesium deprivation.

Echinoderms have an extensive endoskeleton composed of magnesian calcite, a form of calcium carbonate that contains small amounts of magnesium carbonate and occluded matrix proteins [1]. In the frame of the Biomintec European Project focused on the understanding of basic biomineralization mechanisms for the design of novel strategies in nano-biotechnology, we studied the effects of magnesium deprivation on Arbacia lixula sea urchin embryo development. Embryos were morphologically monitored, evaluating developmental abnormalities at different endpoints (3, 6, 24, 48 and 72 hours). In parallel, the spatial transcriptional levels of a skeleton matrix protein (msp130) and the protein synthesis …

Developmental abnormalities induced by Gadolinium causes a time-dependent miss-expression of regulative and structural genes in P. lividus sea urchin embryos

Gadolinium (Gd) is a metal of the lanthanide series of the elements whose chelates are commonly used as contrast agents for magnetic resonance imaging. Its release into the aquatic milieu has posed serious concerns regarding its noxious effects, and therefore Gd is now considered an emerging environmental pollutant. The sea urchin embryo is an excellent model used in both toxicological and developmental research. We analysed the consequences of embryo exposure to sublethal concentrations of Gd on embryo development, focusing on skeletogenesis and developmental symmetry. We observed a strong inhibition of skeleton growth, frequently displayed by an asymmetrical pattern. Continuous exposure t…

Proteolytic activity and MMP-14-like protein levels are affected by Vanadium in Paracentrotus lividus Embryo

The increasing industrial use of vanadium (V), as well as its recent medical use in various pathologies has intensified its environmental release, making it an emerging pollutant [1]. The sea urchin embryo has long been used to study the effects induced by metals, including V. In this study we used an integrated approach that correlates the biological effects on embryo development with proteolytic activities of gelatinases that could better reflect any metal induced imbalances. V-exposure caused morphological/morphometric aberrations, mainly concerning the correct dis-tribution of embryonic cells, the development of the skeleton and the embryo volume [2]. Moreover, V induced a concentration…