Citation:

Doering, J., G. Ankley, B. Blackwell, J. Cavalliin, K. Dean, K. Fay, D. Feifarek, K. Jensen, M. Kahl, C. LaLone, S. Poole, E. Randolph, C. Tilton, AND Dan Villeneuve. Cross-species applicability of a quantitative AOP describing inhibition of aromatase activity leading to reproductive dysfunction in fathead minnow. SETAC North America, Sacramento, CA, November 04 - 08, 2018.

Impact/Purpose:

This is a presentation showing that a previously developed quantitative adverse outcome pathway model based on data collected from the fathead minnow is applicable to some, but not all species of fish. Specifically, this presentation shows that the model is likely applicable to asynchronous spawning fishes, which includes many small-bodied fish such as minnows. However, the model is unlikely to be applicable to group-synchronous or synchronous spawning fishes, which includes most species including catfish, trout, and sturgeon. This work supports aims of CSS project 17.01 towards cross-species extrapolation of adverse effects towards guiding more objective ecological risk assessments of native species of ecological and economic importance in the US.

Description:

Chemicals in the environment can prevent proper reproduction in fish. However, it was unknown whether models developed using data collected from the commonly studied fathead minnow could accurately predict adverse effects to other fish species. Results of our study suggest that the current model can predict adverse effects to certain fish, but not all species of ecological and economic importance in the US. This information will assist in improving models for the regulation of chemicals and in preventing declines in populations of fish.Quantitative adverse outcome pathways (qAOPs) describe quantitative response-response relationships linking the molecular initiating event (MIE) and adverse outcome (AO) to enable quantitative prediction of the probability of occurrence or severity of an AO for a given magnitude of chemical interaction with a MIE. A qAOP has been developed for inhibition of cytochrome P450 aromatase (CYP19) leading to reproductive dysfunction through decreased reduction in circulating estradiol (E2) thereby reducing circulating vitellogenin (VTG). This qAOP was developed based on quantitative data from the fathead minnow (Pimephales promelas). However, different reproductive physiologies exist among fishes and whether a qAOP developed for fathead minnow can predict reproductive dysfunction in other fishes was unknown. Therefore, this study investigated whether this qAOP could accurately predict adverse responses to the model CYP19 inhibitor fadrozole for three other fishes, namely Japanese medaka (Oryzias latipes), zebrafish (Danio rerio), and mosquitofish (Gambusia affinis). Japanese medaka and zebrafish have asynchronous oocyte development in common with fathead minnow, while mosquitofish has group-synchronous oocyte development. In vitro CYP19 inhibition assays demonstrate similar sensitivity to fadrozole among fathead minnow, Japanese medaka, and zebrafish, while CYP19 of mosquitofish was 16-fold more sensitive. Results of 21-day reproductive assays demonstrate quantitatively comparable responses to fadozole for E2, VTG, and egg production among the three asynchronous fishes. In contrast, fadrozole did not reduce E2 or VTG in mosquitofish at any tested concentration and reduction fecundity by only 20% at the greatest concentration tested. In mosquitofish, expression of CYP19 increased by up to 20-fold in the gonad relative to up to 2.5-fold in fathead minnow suggesting that mosquitofish, and potentially other group-synchronous and synchronous species, have greater capacity to compensate through up-regulation of CYP19. Overall, results of this study suggest that the qAOP developed for fathead minnow might be broadly applicable to fishes with asynchronous oocyte development, which includes numerous small-bodied fishes. But, the qAOP is unlikely to be applicable to fishes with group-synchronous or synchronous oocyte development. This information could be essential in guiding more objective ecological risk assessments of aromatase inhibiting chemicals among fishes. The content of this presentation neither constitute nor necessarily reflect US EPA policy.

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