A cross-species model for predicting reproductive dysfunction in fishes exposed to aromatase inhibiting chemicals
Citation:
Doering, J., G. Ankley, B. Blackwell, J. Cavallin, A. Cole, K. Dean, K. Fay, D. Feifarek, K. Jensen, M. Kahl, A. Kittelson, C. Lalone, S. Poole, E. Randolph, C. Tilton, AND D. Villeneuve. A cross-species model for predicting reproductive dysfunction in fishes exposed to aromatase inhibiting chemicals. Twin Ports Early-Career Researchers Symposium, Duluth, MN, March 28, 2019.
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 an MIE. A qAOP has been developed for inhibition of cytochrome P450 aromatase (CYP19) leading to reproductive dysfunction through decreased circulating estradiol (E2) thereby reducing circulating vitellogenin (VTG). This qAOP was developed based on quantitative data from the fathead minnow (Pimephales promelas). However, whether a qAOP developed based on data from fathead minnow could 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. In contrast, mosquitofish have group-synchronous oocyte development which is the prominent strategy among fishes. In vitro CYP19 inhibition assays demonstrate comparable sensitivities to fadrozole among fathead minnow, Japanese medaka, and zebrafish, while CYP19 of mosquitofish is 13-fold more sensitive. Results of 21-day reproductive assays demonstrate comparable quantitative response-response relationships describing fadrozole to E2, E2 to VTG, and VTG to egg production among the asynchronous fishes. However, mosquitofish have complex profiles of sex steroids and steroidogenic enzymes characteristic of group-synchronous oocyte development and exposure to fadrozole causes compensatory responses unique from asynchronous fishes. Overall, these results suggest that the qAOP developed for fathead minnow can broadly predict reproductive dysfunction among fishes with asynchronous oocyte development, which includes numerous small-bodied fishes. But, fishes with group-synchronous oocyte development have different compensatory responses and other modeling challenges which require further investigation towards development of an applicable qAOP. The results of this study could be essential in guiding more objective ecological risk assessments of fishes to aromatase inhibiting chemicals.