Identifying the gaps: Resources and perspectives on the use of nuclear receptor based-assays to improve hazard assessment of emerging contaminants.

Biological control of key processes, such as development and reproduction, is largely ascribed to a superfamily of ligand-dependent and independent transcription factors named Nuclear Receptors (NRs). Given their ability to accommodate ligands, NRs are prime targets of man-made compounds that mimic or antagonise the action of endogenous ligands. Accordingly, NRs occupy a prominent role in OECD and EPA guidelines for testing and assessment of Endocrine disrupting chemicals (EDCs). Although NR assays are already a key instrument in the OECD Conceptual Framework for Testing and Assessment of EDCs, the focus is mostly on vertebrate NRs. Here, we address the chief knowledge gaps in the field. More specifically, we (1) verify the growing availability of genomes/transcriptome projects, (2) highlight gaps in the identification and characterization of metazoan NR and in the establishment of (3) life cycle and (4) toxicity testing protocols. An overall bias towards vertebrates and selected invertebrate groups, notably Arthropoda, Annelida and Mollusca, was observed. Hence, if we aim to improve risk assessment of EDCs and emerging pollutants at an ecosystems scale, and understand their mode of action (MOA), we must establish a framework to include a broad phylogenetic sampling of Metazoans.

The cycling gonad: retinoic-acid synthesis and degradation patterns during adult zebrafish Danio rerio oogenesis.

The expression pattern of genes coding for enzymes of the retinoic acid (RA) synthetic and degradation pathways was characterized in adult female zebrafish Danio rerio. Females were conditioned until maturation and post-spawn expression dynamics were determined. A striking upregulation of cyp26b1, but not cyp26a1, was observed following egg deposition, decreasing to initial levels during recovery. A similar, yet lower, fluctuation was observed for aldh1a2 and rdh10a, the enzymes participating in the two-step RA biosynthesis cascade. The present work highlights the dynamics of the adult D. rerio oogenesis and uncovers novel, yet elusive, metabolic contributors. Possible compartmentalized roles for the different gene paralogue isoforms are discussed.