title: Alteration of neurotransmission and skeletogenesis in sea urchin Arbacia lixula embryos exposed to copper oxide nanoparticles.
abstract: The extensive use of copper oxide nanoparticles (CuO NPs) in many applications has raised concerns over their toxicity on environment and human health. Herein, the embryotoxicity of CuO NPs was assessed in the black sea urchin Arbacia lixula, an intertidal species commonly present in the Mediterranean. Fertilized eggs were exposed to 0.7, 10 and 20ppb of CuO NPs, until pluteus stage. Interferences with the normal neurotransmission pathways were observed in sea urchin embryos. In detail, evidence of cholinergic and serotoninergic systems affection was revealed by dose-dependent decreased levels of choline and N-acetyl serotonin, respectively, measured by nuclear magnetic resonance (NMR)-based metabolomics, applied for the first time to our knowledge on sea urchin embryos. The metabolic profile also highlighted a significant CuO NP dose-dependent increase of glycine, a component of matrix proteins involved in the biomineralization process, suggesting perturbed skeletogenesis accordingly to skeletal defects in spicule patterning observed previously in the same sea urchin embryos. However, the expression of skeletogenic genes, i.e. SM30 and msp130, did not differ among groups, and therefore altered primary mesenchyme cell (PMC) migration was hypothesized. Other unknown metabolites were detected from the NMR spectra, and their concentrations found to be reflective of the CuO NP exposure levels. Overall, these findings demonstrate the toxic potential of CuO NPs to interfere with neurotransmission and skeletogenesis of sea urchin embryos. The integrated use of embryotoxicity tests and metabolomics represents a highly sensitive and effective tool for assessing the impact of NPs on aquatic biota.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cappello
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Vitale
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Oliva
authors.affiliation: CNR-IPCF, Istituto per i Processi Chimico-Fisici, Viale F. Stagno d'Alcontres 37, 98158 Messina, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Villari
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Mauceri
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fasulo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy. Electronic address: mmaisano@unime.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Maisano
mesh_terms: D060105:Animal Shells / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D047308:Arbacia / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002794:Choline / Q000037:antagonists & inhibitors / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005998:Glycine / Q000819:agonists / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008522:Mediterranean Sea; D055432:Metabolomics / Q000379:methods; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009024:Morphogenesis / Q000187:drug effects*; D059326:Serotonergic Neurons / Q000166:cytology / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D012802:Sicily; D013499:Surface Properties; D009435:Synaptic Transmission / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*; D015053:Zygote / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development
chemical_list: D013723:Teratogens; D014874:Water Pollutants, Chemical; D012701:Serotonin; D003300:Copper; D002794:Choline; C006389:N-acetylserotonin; D005998:Glycine; C030973:cupric oxide
keywords: (1)H NMR metabolomics; CuO nanoparticles; Embryotoxicity test; Neurotransmission; Sea urchin; Skeletogenesis; msp130; sm30