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Transcriptional regulation in liver and testis associated with developmental and reproductive effects in male zebrafish exposed to natural mixtures of persistent organic pollutants (POP).

Identifieur interne : 000513 ( Main/Exploration ); précédent : 000512; suivant : 000514

Transcriptional regulation in liver and testis associated with developmental and reproductive effects in male zebrafish exposed to natural mixtures of persistent organic pollutants (POP).

Auteurs : Rasoul Nourizadeh-Lillabadi [Norvège] ; Jan L. Lyche ; Camilla Almaas ; Benedicte Stavik ; S Jannicke Moe ; Mona Aleksandersen ; Vidar Berg ; Kjetill S. Jakobsen ; Nils Chr Stenseth ; Janneche Utne Sk Re ; Peter Alestr M ; Erik Ropstad

Source :

RBID : pubmed:19184727

Descripteurs français

English descriptors

Abstract

Persistent organic pollutants (POP) occur as mixtures in nature and it is difficult to predict the toxicity of such mixtures based on knowledge about toxicity and mechanisms of action for single compounds. The present knowledge on the combined toxic effects and modes of actions of exposure to mixtures is limited. Thus, the scientifically based hazard and risk assessment of POP requires analytical and toxicological data from studies with environmental mixtures of POP. The application of genome wide transcription profiling in toxicology, in combination with classical endpoints, will improve the current understanding of the mechanisms of toxic processes. Furthermore, gene expression data may be useful in establishing new hypothesis and discovering new biomarkers for known toxicity as well as not yet recognized toxicity endpoints. In the present study, developmental and reproductive effects of lifelong exposure to environmental relevant concentrations of two natural mixtures of POP were investigated using classical and molecular methods in a controlled zebrafish model. The mixtures used were extracted from burbot (Lota lota) liver originating from freshwater systems in Norway: one mixture with high levels and one mixture with background levels of polybrominated diphenyl ethers (PBD), polychlorinated biphenyls (PCB), and DDT. The concentration of POP in the zebrafish ranged from levels detected in wild fish from Lake Mjøsa, to concentrations reported in human and wildlife populations. Phenotypic effects observed in both exposure groups included (1) reduced survival, (2) earlier onset of puberty, (3) increased male/female sex ratio, and (4) differences in body weight at 5 mo of age. Interestingly, genome-wide transcription profiling showed changes in regulation of genes involved in endocrine signaling and growth. The transcriptomics changes included (1) key regulator genes for steroid and thyroid hormone functions (cga, ncoa3), (2) insulin signaling and metabolic homeostasis (pik3r1, pfkfb3, ptb1), and (3) p53 activation (mdm4). The effects observed in the experimental zebrafish model raise the question of whether chemical pollution represents a risk to the reproductive health of wild fish inhabiting the freshwater system.

DOI: 10.1080/15287390802537255
PubMed: 19184727


Affiliations:


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<name sortKey="Nourizadeh Lillabadi, Rasoul" sort="Nourizadeh Lillabadi, Rasoul" uniqKey="Nourizadeh Lillabadi R" first="Rasoul" last="Nourizadeh-Lillabadi">Rasoul Nourizadeh-Lillabadi</name>
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<nlm:affiliation>Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway. rasoul.nouri@veths.no</nlm:affiliation>
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<name sortKey="Aleksandersen, Mona" sort="Aleksandersen, Mona" uniqKey="Aleksandersen M" first="Mona" last="Aleksandersen">Mona Aleksandersen</name>
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<title level="j">Journal of toxicology and environmental health. Part A</title>
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<term>Animals (MeSH)</term>
<term>Dose-Response Relationship, Drug (MeSH)</term>
<term>Drug Synergism (MeSH)</term>
<term>Female (MeSH)</term>
<term>Fresh Water (MeSH)</term>
<term>Gadiformes (metabolism)</term>
<term>Gene Expression Profiling (MeSH)</term>
<term>Gene Expression Regulation, Developmental (drug effects)</term>
<term>Liver (chemistry)</term>
<term>Liver (drug effects)</term>
<term>Liver (metabolism)</term>
<term>Longevity (drug effects)</term>
<term>Male (MeSH)</term>
<term>Organic Chemicals (toxicity)</term>
<term>Reproduction (drug effects)</term>
<term>Reproduction (genetics)</term>
<term>Sex Ratio (MeSH)</term>
<term>Sexual Maturation (drug effects)</term>
<term>Testis (drug effects)</term>
<term>Testis (metabolism)</term>
<term>Water Pollutants, Chemical (toxicity)</term>
<term>Zebrafish (physiology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Analyse de profil d'expression de gènes (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Composés chimiques organiques (toxicité)</term>
<term>Danio zébré (physiologie)</term>
<term>Eau douce (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Foie (composition chimique)</term>
<term>Foie (effets des médicaments et des substances chimiques)</term>
<term>Foie (métabolisme)</term>
<term>Gadiformes (métabolisme)</term>
<term>Longévité (effets des médicaments et des substances chimiques)</term>
<term>Maturation sexuelle (effets des médicaments et des substances chimiques)</term>
<term>Mâle (MeSH)</term>
<term>Polluants chimiques de l'eau (toxicité)</term>
<term>Relation dose-effet des médicaments (MeSH)</term>
<term>Reproduction (effets des médicaments et des substances chimiques)</term>
<term>Reproduction (génétique)</term>
<term>Régulation de l'expression des gènes au cours du développement (effets des médicaments et des substances chimiques)</term>
<term>Sexe-ratio (MeSH)</term>
<term>Synergie des médicaments (MeSH)</term>
<term>Testicule (effets des médicaments et des substances chimiques)</term>
<term>Testicule (métabolisme)</term>
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<term>Organic Chemicals</term>
<term>Water Pollutants, Chemical</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>Liver</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr">
<term>Foie</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Gene Expression Regulation, Developmental</term>
<term>Liver</term>
<term>Longevity</term>
<term>Reproduction</term>
<term>Sexual Maturation</term>
<term>Testis</term>
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<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Foie</term>
<term>Longévité</term>
<term>Maturation sexuelle</term>
<term>Reproduction</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Testicule</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Reproduction</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Reproduction</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Gadiformes</term>
<term>Liver</term>
<term>Testis</term>
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<term>Foie</term>
<term>Gadiformes</term>
<term>Testicule</term>
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<term>Danio zébré</term>
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<term>Zebrafish</term>
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<term>Polluants chimiques de l'eau</term>
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<term>Eau douce</term>
<term>Femelle</term>
<term>Mâle</term>
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<div type="abstract" xml:lang="en">Persistent organic pollutants (POP) occur as mixtures in nature and it is difficult to predict the toxicity of such mixtures based on knowledge about toxicity and mechanisms of action for single compounds. The present knowledge on the combined toxic effects and modes of actions of exposure to mixtures is limited. Thus, the scientifically based hazard and risk assessment of POP requires analytical and toxicological data from studies with environmental mixtures of POP. The application of genome wide transcription profiling in toxicology, in combination with classical endpoints, will improve the current understanding of the mechanisms of toxic processes. Furthermore, gene expression data may be useful in establishing new hypothesis and discovering new biomarkers for known toxicity as well as not yet recognized toxicity endpoints. In the present study, developmental and reproductive effects of lifelong exposure to environmental relevant concentrations of two natural mixtures of POP were investigated using classical and molecular methods in a controlled zebrafish model. The mixtures used were extracted from burbot (Lota lota) liver originating from freshwater systems in Norway: one mixture with high levels and one mixture with background levels of polybrominated diphenyl ethers (PBD), polychlorinated biphenyls (PCB), and DDT. The concentration of POP in the zebrafish ranged from levels detected in wild fish from Lake Mjøsa, to concentrations reported in human and wildlife populations. Phenotypic effects observed in both exposure groups included (1) reduced survival, (2) earlier onset of puberty, (3) increased male/female sex ratio, and (4) differences in body weight at 5 mo of age. Interestingly, genome-wide transcription profiling showed changes in regulation of genes involved in endocrine signaling and growth. The transcriptomics changes included (1) key regulator genes for steroid and thyroid hormone functions (cga, ncoa3), (2) insulin signaling and metabolic homeostasis (pik3r1, pfkfb3, ptb1), and (3) p53 activation (mdm4). The effects observed in the experimental zebrafish model raise the question of whether chemical pollution represents a risk to the reproductive health of wild fish inhabiting the freshwater system.</div>
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