Species-specific sensitivity of the fetal testis to mild analgesics

Abstract : The number of environmental chemical contaminants suspected to act as endocrine disruptor compounds by interacting with nuclear receptors (NRs) signaling pathway has been continuously increasing (Hotchkiss et al, 2008). To study such interaction, the use of stable reporter gene assays is relevant, but species-specific in vitro screening assays are lacking to address hazard assessment of chemicals in aquatic vertebrates. Although NR transactivation by chemical ligands is a well conserved mechanism, it is greatly influenced by several intracellular factors such as the promoter context, the cellular context, or the origin species of the receptor. Depending on cell type, one chemical could thus elicit differential response in terms of receptor activation and subsequent gene transcription. In addition, the amino acid composition of the NR, notably in the ligand-binding domain, is also an important source of variation of activity of ligands. This composition varies between NR subtypes from the same species but also between species, yielding significant interspecies differences in NR affinity for chemicals (Matthews et al, 2000 ; Pakdel et al, 1990).In this presentation, we describe the development of stable reporter cell lines based on stable expression of subtypes of human and zebrafish estrogen, androgen and peroxysome proliferator activated γ receptors coupled to NR response element-driven luciferase in human cell lines. The screening of various chemicals from different classes in the different models resulted in different luciferase response patterns and confirm the specificity and conveniency of these in vitro tools for comparative assessment of NRs selective activation by chemicals.
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Caroline Pinto, Marina Grimaldi, Abdelhay Boulahtouf, Anne Riu, Farzad Pakdel, et al.. Species-specific sensitivity of the fetal testis to mild analgesics. 27. Conference of European Comparative Endocrinologists (CECE 2014), Aug 2014, Rennes, France. ⟨ineris-01852879⟩



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