Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.

International audienceFetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk

Impacts of endocrine disrupting chemicals on reproduction in wildlife and humans

Endocrine disrupting chemicals (EDCs) are ubiquitous in aquatic and terrestrial environments. The main objective of this review was to summarize the current knowledge of the impacts of EDCs on reproductive success in wildlife and humans. The examples selected often include a retrospective assessment of the knowledge of reproductive impacts over time to discern how the effects of EDCs have changed over the last several decades. Collectively, the evidence summarized here within reinforce the concept that reproduction in wildlife and humans is negatively impacted by anthropogenic chemicals, with several altering endocrine system function. These observations of chemicals interfering with different aspects of the reproductive endocrine axis are particularly pronounced for aquatic species and are often corroborated by laboratory-based experiments (i.e. fish, amphibians, birds). Noteworthy, many of these same indicators are also observed in epidemiological studies in mammalian wildlife and humans. Given the vast array of reproductive strategies used by animals, it is perhaps not surprising that no single disrupted target is predictive of reproductive effects. Nevertheless, there are some general features of the endocrine control of reproduction, and in particular, the critical role that steroid hormones play in these processes that confer a high degree of susceptibility to environmental chemicals. New research is needed on the implications of chemical exposures during development and the potential for long-term reproductive effects. Future emphasis on field-based observations that can form the basis of more deliberate, extensive, and long-term population level studies to monitor contaminant effects, including adverse effects on the endocrine system, are key to addressing these knowledge gaps

Effects of endocrine disrupting chemicals on gonad development: Mechanistic insights from fish and mammals

Over the past century, evidence has emerged that endocrine disrupting chemicals (EDCs) have an impact on reproductive health. An increased frequency of reproductive disorders has been observed worldwide in both wildlife and humans that is correlated with accidental exposures to EDCs and their increased production. Epidemiological and experimental studies have highlighted the consequences of early exposures and the existence of key windows of sensitivity during development. Such early in life exposures can have an immediate impact on gonadal and reproductive tract development, as well as on long-term reproductive health in both males and females. Traditionally, EDCs were thought to exert their effects by modifying the endocrine pathways controlling reproduction. Advances in knowledge of the mechanisms regulating sex determination, differentiation and gonadal development in fish and rodents have led to a better understanding of the molecular mechanisms underlying the effects of early exposure to EDCs on reproduction. In this manuscript, we review the key developmental stages sensitive to EDCs and the state of knowledge on the mechanisms by which model EDCs affect these processes, based on the roadmap of gonad development specific to fish and mammals

How to design an efficient and robust pipeline for 16S rRNA-gene sequence analysis to improve our understanding on microbial communities?

Voici la composition du Comité d'Organisation (CO) de JOBIM 2015Le Comité Logistique (CL) est présidé par : Philippe LEROY (UMR 1095 INRA/UBP, Unité Génétique, Diversité et Ecophysiologie des Céréales - GDEC, Clermont-Ferrand) Eric PEYRETAILLADE (Université d'Auvergne, Unité EA-CIDAM, Clermont-Ferrand)Trois personnes clefs: Secrétariat JOBIM2015 - Manon MARTINET (LB2MN-EA.CIDAM 4678, Université d'Auvergne) Gestion Administrative - Cathy RESSOT (Direction de la Recherche de l’Innovation et de la valorisation, Université d'Auvergne) Gestion Financière - Isabelle DELPIT (Direction de la Recherche de l’Innovation et de la valorisation, Université d'Auvergne) Le Comité Scientifique (CS) est présidé par : Pierre PEYRET (Université d'Auvergne, Unité EA-CIDAM, Clermont-Ferrand) Jérôme SALSE (MR 1095 INRA/UBP, Unité Génétique, Diversité et Ecophysiologie des Céréales - GDEC, Clermont-Ferrand)Microorganisms are considered one of the most important players involved in different environmental processes and services including nutrient cycling, pollutants attenuation as well as plant, animal and human health. In order to understand the functioning of microbial ecosystems and their impact on ecosystem processes we need to accurately assess their composition and response to environmental constraints. The application of high-throughput sequencing technologies to the study of 16S/18S rRNA-genes has revolutionized the characterization of complex microbial ecosystems. However, although it is now possible to generate hundreds of thousands of sequence reads at low costs, the analysis of the obtained data is still challenging: potential source errors including amplification biases, technical contamination, sequencing artifacts and taxonomical affiliation mistakes can lead to misinterpretations of microbial community diversity. Furthermore, progresses in sequencing technologies produce larger number of sequences at lower cost, but many tools are not scalable and pipelines have to be adapted for huge dataset. With the objective of defining best practices to analyze 16S/18S rRNA-gene sequence data, the Metagenomics, species identification, phylogeny pole of INRA was created to put together experience of biologist, bioinformaticians and statisticians of different laboratories

Guide pratique à destination des biologistes, bioinformaticiens et statisticiens qui souhaitent s’initier aux analyses métabarcoding: Partage de pratiques et retours d'expérience des membres du pôle métagénomique du PEPI IBIS

National audienceLes méthodes d’analyse métabarcoding (également appelées métagénomique ciblée ou amplicon) sontde plus en plus utilisées pour étudier la diversité des espèces présentes dans un écosystème (micro organismes,plantes, animaux). Le principe consiste à extraire l’ADN d’un échantillon environnemental puis à amplifier par PCR un fragment cible à l’aide d’un couple d’amorces prédéfini. Ces produits PCR, après ajouts de barcodes(oligonucléotides uniques pour chaque échantillon) et adaptateurs de séquençage, sont ensuite séquencés. Après le séquençage, les séquences sont triées par échantillon grâce aux barcodes puis assignées à des taxons par comparaison avec des séquences de référence. Beaucoup de méthodes et outils d’analyse ont été développés pour obtenir une vision la plus précise possible des écosystèmes étudiés. Les techniques de préparation puis d’analyse des échantillons dépendent de l’écosystème, des questions auxquelles on souhaite répondre et de la technologie de séquençage utilisée. Nous proposons des conseils issus de nos expériences, discussions et lectures bibliographiques afin de guider les lecteurs depuis la planification expérimentale jusqu’à l’analyse des données, en détaillant les points de vigilance à chaque étape