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Differential sensitivity to in vitro inhibition of cytochrome P450 aromatase (CYP19) activity among 18 freshwater fishes
Citation:
Doering, J., Dan Villeneuve, K. Fay, E. Randolph, K. Jensen, M. Kahl, C. LaLone, AND G. Ankley. Differential sensitivity to in vitro inhibition of cytochrome P450 aromatase (CYP19) activity among 18 freshwater fishes. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 170(2):394-403, (2019). https://doi.org/10.5061/dryad.nn94830
Impact/Purpose:
This publication shows that intrinsic differences in sensitivity to inhibition of aromatase could be greater than 50-fold among species of fish. Further, this publication shows that species of fish of significant ecological or economic importance in the US, such as catfish, trout, perch, and sturgeon, could be much more sensitive to impairment of reproduction relative to the laboratory model species typically used for toxicity assessments, such as fathead minnows. This work supports aims of CSS project 17.01 toward understanding cross-species differences in sensitivity to anthropogenic contaminants and the mechanisms that drive those differences in order to guide more objective ecological risk assessments.
Description:
There is significant concern regarding potential impairment of fish reproduction associated with endocrine disrupting chemicals. Aromatase (CYP19) is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase by chemicals can result in reduced concentrations of estrogens leading to adverse reproductive effects. These effects have been extensively investigated in a small number of laboratory model fishes, but differences in sensitivity among species is largely unknown. Therefore, this study took a first step towards understanding potential differences in sensitivity to aromatase inhibitors among fishes. Specifically, a standard in vitro aromatase inhibition assay using subcellular fractions of whole tissue homogenates was used to evaluate the potential sensitivity of eighteen phylogenetically diverse species of freshwater fish to the nonsteroidal aromatase inhibitor fadrozole. Sensitivity to fadrozole ranged by more than 52-fold among these species. Five species were further investigated for sensitivity to up to four additional nonsteroidal aromatase inhibitors, letrozole, imazalil, prochloraz, and propiconazole. Potencies of each of these chemicals relative to fadrozole ranged by up to two orders of magnitude among the five species. Commonly investigated laboratory model species were among the least sensitive to all the investigated chemicals; therefore, ecological risks of aromatase inhibitors derived from these species might not be adequately protective of more sensitive native fishes. This information could guide more objective ecological risk assessments of native fishes to chemicals that inhibit aromatase.
URLs/Downloads:
DOI: Differential sensitivity to in vitro inhibition of cytochrome P450 aromatase (CYP19) activity among 18 freshwater fishes