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Integrated modelling of endocrine disruption in zebrafish at different biological levels (MOZAIC)

Abstract

Certain chemicals possess the ability of modulating the endocrine systems, associated with reproductive and developmental dysfunctions and abnormal levels of circulating steroids hormones. There have been increasing concerns regarding endocrine disrupting chemicals (EDCs) and their potential harmful effects on humans and wildlife, including fish. Among model species for ecotoxicological investigations, zebrafish is a vertebrate organism extensively used for scientific purposes and an increasing amount of (eco)-toxicological data of EDCs toward zebrafish have been gathered during the past years. The translation of subtle functional deficits within individuals into population-level effects is a challenge for the ecotoxicological risk assessment of EDCs. Mathematical models can provide the framework in which the effects on many endpoints and the cross regulations between these endpoints can be integrated. The aim of MOZAIC project is to develop an integrated modelling framework for zebrafish to assess how EDCs modify the level of hormones in individuals (with inclusion of regulations in the model) and how such disruption will impact individual fitness and population dynamics. To this purpose, we propose to develop and to integrate three models: (i) hypothalamicpituitary- gonadal (HPG) axis model for male and female zebrafish, (ii) Physiologically-based pharmacokinetic (PBPK) models for zebrafish for a panel of EDCs, and (iii) an agent-based model for a relevant description of zebrafish population dynamics and of its perturbation due to exposure to EDCs. Our final goal is to relate hormone levels to effects on reproduction in zebrafish using relevant dose responses. The calibration of the models will be based on available data, on new QSAR models and on new experimental data on the zebrafish reproductive physiology. Experimental data will be acquired to fulfil the two main gaps identified in the literature: variation of sex steroid concentrations during the reproductive cycles in control conditions and when exposed to an EDC. In fine, MOZAIC project will provide an integrated generic (i.e. not restricted to a single chemical) model linking the effects of EDCs at cellular, organism and population levels. This model could be applied to different endocrine disruptor compounds to assess long-term consequences of an endocrine disruption.

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Dates and versions

ineris-00971018 , version 1 (02-04-2014)

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Cite

Rémy Beaudouin, François Brion, Alexandre R.R. Pery, Enrico Mombelli, Céline Brochot, et al.. Integrated modelling of endocrine disruption in zebrafish at different biological levels (MOZAIC). 1. European Conference on the Replacement, Reduction and Refinement of Animal Experiments in Ecotoxicology, Jun 2012, Dübendorf, Switzerland. ⟨ineris-00971018⟩

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