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Assessing effects of aromatase inhibition on fishes with group-synchronous oocyte development using western mosquitofish (Gambusia affinis) as a model
Citation:
Doering, J., Dan Villeneuve, C. Tilton, A. Kittelson, B. Blackwell, M. Kahl, K. Jensen, S. Poole, J. Cavallin, A. Cole, K. Dean, C. LaLone, AND G. Ankley. Assessing effects of aromatase inhibition on fishes with group-synchronous oocyte development using western mosquitofish (Gambusia affinis) as a model. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 232:105741, (2021). https://doi.org/10.1016/j.aquatox.2020.105741
Impact/Purpose:
Predictive models and frameworks for linking inhibition of the enzyme aromatase, as measured in non-animal high throughput screening assays, to adverse effects on reproduction in fish have been established. However, those models were established using data from several fish species commonly reared in the laboratory that employ a particular reproductive strategy involving asynchronous oocyte development and repeat spawning. Many fish species employ synchronous oocyte development and spawn annually. This product was intended to help address the question of whether the current approaches for predicting impacts of aromatase inhibitors are applicable to fish with a synchronous/annual spawning reproduction strategy. The study establishes the mosquitofish as a viable laboratory model with synchronous oocyte development and provides preliminary evidence that exposure to aromatase inhibitors during a critical period of the reproductive cycle can lead to adverse effects on fish reproduction. This research aids the understanding of the capabilities and limitations of the current predictive models for aromatase inhibition which can help EPA scientists from OPPT, OW, and the Regions better utilize high throughput screening information pertaining to aromatase inhibition to make decisions regarding putative endocrine active chemicals.
Description:
Exposure to certain anthropogenic chemicals can inhibit the activity to cytochrome P450 aromatase (CYP19) in fishes leading to decreased plasma 17β-estradiol (E2), plasma vitellogenin (VTG), and egg production. Reproductive dysfunction resulting from exposure to aromatase inhibitors has been extensively investigated in several laboratory model species of fish. These model species have ovaries that undergo asynchronous oocyte development, but many native fishes of regulatory concern have ovaries with group-synchronous oocyte development. Fishes with group-synchronous oocyte development have dynamic reproductive cycles which typically occur annually and are often triggered by complex environmental cues which has resulted in a lack of test data and uncertainty regarding sensitivities to and adverse effects of aromatase inhibition. The present study used the western mosquitofish (Gambusia affinis) as a laboratory model to investigate adverse effects of chemical aromatase inhibition on group-synchronous oocyte development. Adult female western mosquitofish were exposed to either 0, 2, or 30 μg/L of the model nonsteroidal aromatase inhibiting chemical, fadrozole, for a complete reproductive cycle. Fish were sampled at four time-points representing pre-vitellogenic resting, early vitellogenesis, late vitellogenesis/early ovarian recrudescence, and late ovarian recrudescence. Temporal changes in numerous reproductive parameters were measured, including gonadosomatic index (GSI), plasma sex steroids, and expression of selected genes in the brain, liver, and gonad that are important for reproduction. In contrast to fish from the control treatment, fish exposed to 2 and 30 μg/L of fadrozole had persistent elevated expression of CYP19 in the ovary, depressed expression of VTG in the liver, and a low GSI. These responses suggest that completion of a group-synchronous reproductive cycle was unsuccessful during the assay in fish from either fadrozole treatment. This adverse effects data suggests that exposure to aromatase inhibitors has the potential to cause reproductive dysfunction in a wide range of native fishes with both asynchronous and group-synchronous reproductive strategies.
URLs/Downloads:
DOI: Assessing effects of aromatase inhibition on fishes with group-synchronous oocyte development using western mosquitofish (Gambusia affinis) as a model