Multi-omic approach to evaluate the response of gilt-head sea bream (Sparus aurata) exposed to the UV filter sulisobenzone

Sulisobenzone (BP-4) is one of the benzophenone type UVfiltersmost frequently detected in aquatic ecosystems. As a suspected endocrine disrupting compound, scarce information is available yet about other molecular effects and its mechanismof action. Here, we used an integrated transcriptomic and metabolomic approach to improve the current understanding on the toxicity of BP-4 towards aquatic species. Gilt-head sea bream individualswere exposed at environmentally relevant concentrations (10 μg L-1) for 22 days. Transcriptomic analysis revealed 371 differentially expressed genes in liver while metabolomic analysis identified 123 differentially modulated features in plasma and 118 in liver. Integration of transcriptomic and metabolomic data showed disruption of the energy metabolism(>10 pathways related to the metabolismof amino acids and carbohydrateswere impacted) and lipid metabolism (5 glycerophospholipids and the expression of 3 enzymes were affected), suggesting oxidative stress.We also observed, for the first time in vivo and at environmental relevant concentrations, the disruption of several enzymes involved in the steroid and thyroid hormones biosynthesis. DNA and RNA synthesis was also impacted by changes in the purine and pyrimidine metabolisms. Overall, the multiomic workflow presented here increases the evidence on suspected effects of BP-4 exposure and identifies additional modes of action of the compounds that could have been overlooked by using single omic approaches. ©2021 The Authors. Published by Elsevier B.V.This research was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTM2015-70731-R) and the FPI fellowship (BES-2016-078593). The authors also would like to acknowledge the Laboratory of Aquaculture at the Faculty of Marine and Environmental Sciences (University of Cádiz), Thibaut Dumas and David Rosain (UMR HydroSciences, Université Montpellier, France) for their support

Coherent combining of two high-brightness laser diodes phase-locked by a Michelson-type external cavity (Orale)

International audienceWe describe a new coherent beam combin- ing architecture based on the passive phase- locking of two laser diodes in a Michelson external cavity on their rear side, and their coherent combination on their front side

Etude des effets de la venlafaxine sur Mytilus galloprovincialis par une approche métabolomique

National audienceLa problématique des contaminants émergents fait l'objet d'une considération croissante depuis leur mise en évidence dans l'environnement grâce aux avancées techniques. Parmi ces contaminants, les produits pharmaceutiques sont continuellement rejetés dans l’environnement au travers des stations d'épuration du fait de leur consommation (Santos et al., 2010). La venlafaxine (VEN) est un antidépresseur utilisé pour soigner la dépression et divers troubles de l'anxiété (Noordam et al., 2015). Son mode d'action (MoA) thérapeutique la modulation de la neurotransmission du cerveau humain en bloquant les transporteurs de sérotonine et noradrénaline sur les neurones présynaptiques pour augmenter leur disponibilité (Nelson, 2010). Bien que peu détectée dans l'eau de mer (Alygizakis et al., 2016), la VEN a pu être quantifiée à des concentrations comprises entre 3,0 ng/g (Martínez Bueno et al., 2014) et 36,1 ng/g dans des mollusques collectés sur les côtes européennes avec un taux de détection de 100% (Alvarez-Muñoz et al., 2015a; Álvarez-Muñoz et al., 2015b). La présence de résidus de VEN dans des mollusques marins pose la question de ses effets chez ces organismes même à de faibles doses d’exposition. Il a été montré que la VEN pouvait avoir un impact sur la reproduction (Galus et al., 2013), le comportement de prédation (Bidel et al., 2016 ; Bisesi et al., 2014 ; Painter et al., 2009) et la réponse au stress (Best et al., 2014 ; Ings et al., 2012).L'objectif de cette étude est d'étudier les effets moléculaires de la VEN sur Mytilus galloprovincialis par une approche métabolomique, ce type d’étude ayant déjà démontré son potentiel pour mettre en évidence les effets moléculaires d’une exposition à un xénobiotique (Campillo et al., 2019; Ji et al., 2016). Pour cet objectif, 49 moules ont été acclimatées 7 jours puis 26 ont été exposées pendant 3 jours à 10 µg/L de venlafaxine. Les dissections ont eu lieu à J1 et J3 pour prélever les glandes digestives et l’analyse a été réalisée par LC-HRMS pour générer des empreintes métaboliques à comparer entre contrôles et exposés.Après tri des données, 1336 signaux ont été détectés en mode négatif, dont 451 sont sur-modulés et 309 sous-modulés lorsqu'on compare les exposés aux contrôles sur les deux jours. La sérotonine ainsi que la dopamine ont été annotées, ce qui permet de supposer que le MoA de la VEN chez la moule est semblable à celui chez l’Homme. Il semblerait donc qu'une exposition à la VEN ait un effet sur le métabolome de Mytilus galloprovincialis, malgré la courte période d'exposition. Il convient maintenant de définir plus précisément l’identité des métabolites modulés pour mettre en avant les principales voies métaboliques impactées et ainsi émettre des hypothèses sur les fonctions biologiques pouvant être perturbées par une exposition

Early Biological Modulations Resulting from 1-Week Venlafaxine Exposure of Marine Mussels Mytilus galloprovincialis Determined by a Metabolomic Approach

International audienceThere is growing evidence of the presence of pharmaceuticals in natural waters and their accumulation in aquatic organisms. While their mode of action on non-target organisms is still not clearly understood, their effects warrant assessment. The present study assessed the metabolome of the Mediterranean mussel (Mytilus galloprovincialis) exposed to a 10 µg/L nominal concentration of the antidepressant venlafaxine (VLF) at 3 time-points (1, 3, and 7 days). Over the exposure period, we observed up- or down-modulations of 113 metabolites, belonging to several metabolisms, e.g., amino acids (phenylalanine, tyrosine, tryptophan, etc.), purine and pyrimidine metabolisms (adenosine, cyclic AMP, thymidine, etc.), and several other metabolites involved in diverse functions. Serotonin showed the same time-course modulation pattern in both male and female mussels, which was consistent with its mode of action in humans, i.e., after a slight decrease on the first day of exposure, its levels increased at day 7 in exposed mussels. We found that the modulation pattern of impacted metabolites was not constant over time and it was gender-specific, as male and female mussels responded differently to VLF exposure

Mixture effects of pharmaceuticals carbamazepine, diclofenac and venlafaxine on Mytilus galloprovincialis mussel probed by metabolomics and proteogenomics combined approach

The technical assistance of Mélodie Kielbasa (Atomic Energy and Alternative Energies Commission, CEA, Bagnols-sur-Cèze, France) and proof-reading assistance of David Manley are gratefully acknowledged.International audienceExposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active compounds (PhACs) on non-target organisms. However, not taking the co-occurrence of contaminants in the environment and their possible interactions into account may lead to underestimation of their impacts. In this study, we combined untargeted metabolomics and proteogenomics approaches to assess the mixture effects of diclofenac, carbamazepine and venlafaxine on marine mussels (Mytilus galloprovincialis). Our multi-omics approach and data fusion strategy highlighted how such xenobiotic cocktails induce important cellular changes that can be harmful to marine bivalves. This response is mainly characterized by energy metabolism disruption, fatty acid degradation, protein synthesis and degradation, and the induction of endoplasmic reticulum stress and oxidative stress. The known MeOAs and molecular signatures of PhACs were taken into consideration to gain insight into the mixture effects, thereby revealing a potential additive effect. Multi-omics approaches on mussels as sentinels offer a comprehensive overview of molecular and cellular responses triggered by exposure to contaminant mixtures, even at environmental concentrations