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Project title
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Assessment of the effects of aromatase inhibitors and solvents by means of an in vitro assay
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Project management
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Prof. Dr. Patricia Holm, Head of MGU and Maria a Marca, PhD student, both Department of Environmental Sciences, University of Basel |
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Abstract
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The aim of this project is to develop an in vitro assay to assess the effects of endocrine disruptors that target the steroidogenic pathway. Gonadal organ cultures will be obtained from two species, the brown trout (Salmo trutta, a representative Swiss species) and the fathead minnow (Pimephales promelas, a laboratory standard species). The culture will be carried out collecting the immature gonads from these two species and their relative sensitivity to several endocrine disruptors will be studied. Endocrine disruptors are widely distributed in the environment and show high activity even at low concentrations. This raises concern about potential impairment of the wildlife. The in vitro systems have the advantages to be valuable to study toxicological effects and to reduce the numerous unknown factors that occur during in vivo studies. Moreover they are rapid and cost-effective tools.
The organ culture will be used to determine the effects of aromatase inhibitors (AIs). The cytochrome P450 aromatase enzyme is responsible for the final step of the biosynthesis of estrogens and its activity can be blocked by the AIs. Several in vivo studies on fish showed that AIs could generate adverse reproductive and developmental effects in fishes such as oocyte atresia, reduction of fecundity and masculinization. On this basis negative effects of AIs are expected on the gonadal organ culture. The in vitro assay of immature gonads will allow to identify potential immediate morphological alterations and some physiological and molecular processes induced by the AIs during the gonadal differentiation.
Later on the organ culture will also serve to test the effects of selected organic solvents. These compounds are currently used in aquatic toxicity testing in order to achieve more effective dispersion of low soluble toxicants. The OECD recommends a maximum solvent concentration of 100 μl/L. However several studies revealed that some of these carrier solvents might affect the reproduction of certain fish species at very low concentrations and therefore complicate the interpretation and defence of studies on endocrine disruptors. The mechanisms of action these organic solvents have not been fully elucidated. There is some evidence that carrier solvents can have a consequence on cytochrome P450 enzymes activity. Combinations of solvents and AIs will consequently be tested on the organ culture to investigate the potential action of these mixtures on the steroidogenic pathway. The organ culture in vitro assay will permit to better understand the mode of action of some solvents and to inform on the appropriateness of carrier solvents for use in fish endocrine assay. |
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