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EMSG46: Characterization of testicular toxicity using traditional and omic tools

Principal Investigator

Dr. David Rouquié
355, Rue Dostoí¯evski, BP 153
06560 Sophia Antipolis Cedex
France
Tel: + 33 4 92 94 34 76
Fax: + 33 4 93 95 84 54

Collaborators

Helen Tinwell, Rémi Bars - BCS, France
Pascal  Girard, Pascal Roy - Centre Hospitalier Lyon - Sud, France
Claire Mauduit, Mohamed Benahmed - INSERM U670
Peter Mc Cahon, Dominique Rosati, Patrick Bardel - BCS-D-ROCS

Description

The aim of this project is to characterize adult rat testicular toxicity induced by compounds that have either an estrogenic or a non-estrogenic mode of action. To fully realise this goal, the differentiation between normal background variability (ie no effect), an adaptive change and an adverse effect due to treatment (both in terms of dose level and treatment duration) must be established for each of the compounds investigated. The type of data collected will include gravimetric and hormonal changes, assessment of histopathological lesions and identifying changes in gene expression. At the end of the project, therefore, a comprehensive profile of rat testicular toxicity as a function of time and dose level will have been established, using traditional and molecular tools, for three compounds.  To succeed in this endeavour, a number of objectives, as described below, must be achieved:

1. Establish background variation in gene expression (for genes found to be affected by compounds investigated in the project)

2. Establish a dose-response progression from no effect to adaptive change to adverse toxicological effects

3. Establish a time dependent progression from no effect to adaptive change to adverse toxicological effects

4. Comparison of estrogenic and non-estrogenic modes of action on the testis

5. Comparison of strong and weak estrogenic compounds

6. Establishment of biomarkers of testicular toxicity

Related Publications

Sophie Ludwig, Helen Tinwell, Frédéric Schorsch, Christel Cavaillé, Marc Pallardy, David Rouquié,  Rémi Bars (2011).  A molecular and phenotypic integrative approach to identify a no-effect dose level for anti-androgen induced testicular toxicity.  Toxicological Sciences. Jul; 122 (1): 52-63.

Sophie Ludwig, Helen Tinwell, David Rouquié, Frédéric Schorsch, Marc Pallardy, Rémi Bars Potential new targets involved in 1,3-dinitrobenzene induced testicular toxicity.  In preparation

Timeline: January 2008 > December 2010

LRI funding: €1,300,000

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