In search for molecular players underlying altered physiology and behavior caused by (neuro)endocrine disrupting compounds in zebrafish by differential peptidomics and proteomics.

The increasing impact of human activities on the environment has world-wide consequences, especially when chemical pollutions are concerned. Endocrine disruptors are considered as Substances of Very High Concern (SVHC) because they interfere with endocrine systems or lead to adverse developmental, reproductive or neurological effects in both wildlife and humans. These endocrine disrupting compounds (EDCs) can be found in many products including toys, detergents, flame retardants, cosmetics and pesticides and have a widespread presence in aquatic environments. Though effects on organismal physiology and behavior have been studied for some EDCs, it remains a major challenge to understand underlying molecular or cellular mechanisms which are often required to determine guidelines for hazard and risk assessment. A second major challenge in ecotoxicology is to find valid biomarkers (at molecular, physiological or behavioral level) to assess the environmental status and to develop bio-assays that are predictive for aversive effects at higher levels of organization in an early stage.Peptidergic signaling molecules can be found in all metazoans, where they regulate diverse physiological processes and behaviors. Therefore, disturbances in peptide homeostasis (e.g. as a consequence of pollutions) are often reflected on the level of overall physiology and behavior (growth, fitness, feeding, reproduction,...). Therefore, (bioactive) peptides might be attributed as valid biomarkers. We will use LC-MS-based differential peptidomics approaches to identify, characterize and quantify peptides in zebrafish that were challenged with selected (neuro)EDC. In addition, changes on the protein level will be assessed by differential proteomics techniques while swimming behavior, critical swimming speed, instant fuel use and aerobic scope will be determined to monitor physiological and behavioral effects. By adopting these interdisciplinary approaches, we aim at identifying and characterizing (physiological and molecular) biomarkers, as early warning systems of disturbance due to EDC exposure. Because the zebrafish Danio rerio is an important vertebrate model system, our mechanistic results are likely to provide important insights of toxicological or biomedical relevance as well.

Keywords:PROTEOMICS, ENDOCRINE DISRUPTION, MASS SPECTROMETRY, NEUROPEPTIDES

Disciplines:Animal biology, Biochemistry and metabolism, General biology, Medical biochemistry and metabolism, Veterinary medicine