Ex vivo assessment of testicular toxicity induced by carbendazim and iprodione, alone or in a mixture
| Autor: | Odette Prat, Philippe Durand, Sébastien Voisin, Cédric Pisani, Philippe Bulet, Karim Arafah, Marie-Roberte Guichaoua, Marie-Hélène Perrard |
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| Přispěvatelé: | Communications Cellulaires et Différenciation (CCD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Atheris Laboratories, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANSES, the French Agency for Food, Environmental and Occupational Health Safety [EST-2010-2-019], École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male 010501 environmental sciences Proteomics 01 natural sciences Transcriptome Toxicology Rats Sprague-Dawley Tissue Culture Techniques rat Sperm motility ComputingMilieux_MISCELLANEOUS Sex Chromosome Aberrations spermatogénèse glande endocrine General Medicine endocrine disruption Seminiferous Tubules infertilité Medical Laboratory Technology Meiosis toxicogenomics testicule biomarker Steroids [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology toxicogénomique biomarqueur Motility Biology Animal Testing Alternatives Testicular Diseases Andrology 03 medical and health sciences Toxicity Tests Animals Spermatogenesis pesticides spermatogenesis pesticide 0105 earth and related environmental sciences Pharmacology fongicide Hydantoins [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology Aminoimidazole Carboxamide Biomarker (cell) Fungicides Industrial Rats 030104 developmental biology ex vivo Benzimidazoles Carbamates [SDE.BE]Environmental Sciences/Biodiversity and Ecology Toxicogenomics Ex vivo |
| Zdroj: | ALTEX-Alternatives to Animal Experimentation ALTEX-Alternatives to Animal Experimentation, 2016, 33 (4), pp.393--413. ⟨10.14573/altex.1601253⟩ ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION, 2016, 33 (4), pp.393--413. ⟨10.14573/altex.1601253⟩ Alternatives to Animal Experimentation 4 (33), 393-413. (2016) Altex-Heidelberg Altex-Heidelberg-, Elsevier, 2016, ⟨10.14573/altex.1601253⟩ |
| ISSN: | 1868-8551 1868-596X 0946-7785 |
| DOI: | 10.14573/altex.1601253⟩ |
| Popis: | International audience; To measure the testicular toxicity of two fungicides (carbendazim and iprodione), alone or in a mixture, we used a rat ex vivo model of seminiferous tubules, greatly reducing the number of rodents used, in accordance with the 3R rule (Replacement, Reduction, and Refinement). This model allows the representation of puberty, a critical life period with regard to endocrine disruptors. The cellular modifications were followed for three weeks through transcriptomic and proteomic profiling analysis. A quantitative and comparative method was developed to estimate how known pathways were disturbed by each substance. This pathway-driven analysis revealed a strong alteration of steroidogenesis and an impairment of meiosis in all cases, albeit the initial molecular events were different for both substances. The ex vivo cytogenetic analysis confirmed that both fungicides alter the course of the first meiotic prophase. In addition, the mixture of both substances triggered effects greater than the sum of their cumulative effects and compromised future sperm motility after a shorter time of exposure compared with the fungicides tested separately. The alliance of an ex vivo culture with omics strategies complemented with a physiological examination is a powerful combination of tools for testing substances, separately or in a mixture, for their testicular toxicity. In particular, proteomics allowed the identification of systematically differentially expressed proteins in the secretomes of exposed cultures, such as FUCO and PEBP1, two proteins linked with the motility and fertilizing ability of spermatozoa, respectively. These proteins may be potential biomarkers of testicular dysfunction and infertility. |
| Databáze: | OpenAIRE |
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