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Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow
Bencic, D., Dan Villeneuve, A. Biales, L. Blake, E. Durhan, K. Jensen, M. Kahl, L. Makynen, D. Martinovic-Weigelt, AND G. Ankley. Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 32(8):1828-1834, (2013).
The purpose of the present study was to utilize an adaptation of the 21 d FHM reproduction assay developed for the US Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP) [40,41] to examine the effects of FIP on numerous HPG axis and reproductive parameters in adult FHMs, including reproductive output, circulating steroids and vitellogenin, gonadal steroid production, gonadal histology, and targeted gene expression. These data provided the first test of a hypothesized adverse outcome pathway linking antagonism of the GABAAR with reproductive impairments in fish. Additionally, the study provided an opportunity to characterize the utility of the 21 d FHM test for detecting and diagnosing neuroendocrine disruption as a mode of reproductive endocrine disruption. Finally, the study provides useful data concerning the potential hazards associated with environmentally-relevant concentrations of a widely used pesticide frequently detected in the aquatic environment.
Gamma aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic pituitary gonadal (HPG) axis, leading to impaired fish reproduction. The present study used a 21 d fathead minnow (FHM; Pimephales promelas) reproduction assay to investigate the reproductive toxicity of fipronil (FIP), a broad-spectrum phenylpyrazole insecticide that acts as a non-competitive blocker of GABA receptor-gated chloride channels. Continuous exposure to up to 5 µg FIP/L had no significant effect on most of the endpoints measured, including fecundity, secondary sexual characteristics, plasma steroid and vitellogenin concentrations, ex vivo steroid production, and targeted gene expression in gonads or brain. The gonad mass, gonadosomatic index (GSI), and histological stage of the gonad were all significantly different in females exposed to 0.5 µg FIP/L compared to those exposed to 5.0 µg FIP/L; however, there were no other significant effects on these measurements in the controls or any of the other treatments, in either males and females. Overall, our results do not support a hypothesized adverse outcome pathway linking FIP antagonism of the GABA receptor(s) to reproductive impairment in fish.