An integrated omic analysis of hepatic alteration in medaka fish chronically exposed to cyanotoxins with possible mechanisms of reproductive toxicity.
Cyanobacterial blooms threaten human health as well as the population of other living organisms in the aquatic environment, particularly due to the production of natural toxic components, the cyanotoxin. So far, the most studied cyanotoxins are microcystins (MCs). In this study, the hepatic alterations at histological, proteome and transcriptome levels were evaluated in female and male medaka fish chronically exposed to 1 and 5 μg L-1microcystin-LR (MC-LR) and to the extract of MC-producing Microcystis aeruginosa PCC 7820 (5 μg L-1of equivalent MC-LR) by balneation for 28 days, aiming at enhancing our understanding of the potential reproductive toxicity of cyanotoxins in aquatic vertebrate models. Indeed, both MC and Microcystis extract adversely affect reproductive parameters including fecundity and egg hatchability. The liver of toxin treated female fish present glycogen storage loss and cellular damages. The quantitative proteomics analysis revealed that the quantities of 225 hepatic proteins are dysregulated. In particular, a notable decrease in protein quantities of vitellogenin and choriogenin was observed, which could explain the decrease in reproductive output. Liver transcriptome analysis through Illumina RNA-seq reveals that over 100-400 genes are differentially expressed under 5 μg L-1MC-LR and Microcystis extract treatments, respectively. Ingenuity pathway analysis of the omic data attests that various metabolic pathways, such as energy production, protein biosynthesis and lipid metabolism, are disturbed by both MC-LR and the Microcystis extract, which could provoke the observed reproductive impairment. The transcriptomics analysis also constitutes the first report of the impairment of circadian rhythm-related gene induced by MCs. This study contributes to a better understanding of the potential consequences of chronic exposure of fish to environmental concentrations of cyanotoxins, suggesting that Microcystis extract could impact a wider range of biological pathways, compared with pure MC-LR, and even 1 μg L-1MC-LR potentially induces a health risk for aquatic organisms.
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France. Electronic address: qqin@mnhn.fr.
Qin
Q
Qiao
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Séverine
S
Le Manach
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France; Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, BioPôle Alfort, 94700 Maisons-Alfort, France.
Hélène
H
Huet
UMR 7221 CNRS/MNHN, Évolution des Régulations Endocriniennes, Sorbonne Universités, Muséum Nationale d'Histoire Naturelle, Paris, France.
Evelyne
E
Duvernois-Berthet
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Soraya
S
Chaouch
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Charlotte
C
Duval
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Benoit
B
Sotton
UMR 7196 MNHN/CNRS, INSERM U1154, Sorbonne Universités, Museum National d'Histoire Naturelle, Paris, France.
Loïc
L
Ponger
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Arul
A
Marie
Institut de Biologie Paris Seine/FR 3631, Plateforme Spectrométrie de masse et Protéomique, Institut de Biologie Intégrative IFR 83, Sorbonne Universités, Université Pierre et Marie Curie, 75005 Paris, France.
Lucrèce
L
Mathéron
Waters Corporation, Manchester, United Kingdom.
Sarah
S
Lennon
Institut de Biologie Paris Seine/FR 3631, Plateforme Spectrométrie de masse et Protéomique, Institut de Biologie Intégrative IFR 83, Sorbonne Universités, Université Pierre et Marie Curie, 75005 Paris, France.
Gérard
G
Bolbach
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Chakib
C
Djediat
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Cécile
C
Bernard
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France.
Marc
M
Edery
UMR 7245 MNHN/CNRS Molécules de Communication et Adaptation des Micro-organismes, Sorbonne Universités, Muséum National d'Histoire Naturelle, CP 39, 12 Rue Buffon, 75005 Paris, France. Electronic address: bmarie@mnhn.fr.
Benjamin
B
Marie
D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D002457:Cell Extracts / Q000008:administration & dosage / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005393:Fish Diseases / Q000139:chemically induced*; D006003:Glycogen / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D052998:Microcystins / Q000008:administration & dosage / Q000633:toxicity*; D046931:Microcystis / Q000737:chemistry*; D009990:Oryzias / Q000502:physiology*; D052287:Oviparity / Q000187:drug effects / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects; D020543:Proteome / Q000187:drug effects / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects
D001427:Bacterial Toxins; D002457:Cell Extracts; D052998:Microcystins; D020543:Proteome; C078588:microcystin; D006003:Glycogen
Hepatic circadian rhythm perturbation; Ingenuity pathway analysis; Microcystins; Microcystis aeruginosa PCC 7820; Proteomics; Transcriptomics