Effects of bifenthrin exposure on the estrogenic and dopaminergic pathways in zebrafish embryos and juveniles

Abstract

Bifenthrin is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of bifenthrin increased plasma concentrations of 17b-estradiol (E2) and altered the expression of dopaminergic pathway components. The dopaminergic neurons can indirectly regulate E2 biosynthesis, suggesting that bifenthrin may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Because embryos do not have a complete HPG axis, the hypothesis that bifenthrin impairs dopamine regulation was tested in embryonic and 1-mo-old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0.34 and 3.1 mg/L bifenthrin for 96 h. Quantitative reverse transcriptase polymerase chain reaction was used to investigate transcripts of tyrosine hydroxylase (TH), dopamine receptor 1 (DR1) and 2A (DR2A), dopamine active transporter (DAT), estrogen receptor a (ERa), ERb1, ERb2, luteinizing hormone b (LHb), follicle-stimulating hormone b (FSHb), vitellogenin (VTG), cytochrome P450 cyp19a1a, and cyp19a1b. Levels of E2 were measured by enzyme-linked immunosorbent assay (ELISA). Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured by liquid chromatrography-tandem mass spectrometry (LC-MS/MS). Significant decreases in TH and DR1 transcripts and HVA levels, as well as ratios of HVA/dopamine and HVAþDOPAC/dopamine, in zebrafish embryos were observed after bifenthrin treatment. In juveniles, a significant increase in the expression of ERb1 and the DOPAC to dopamine ratio was noted. These results show a possible antiestrogenic effect of bifenthrin in embryos, and estrogenicity in juveniles, indicating life-stage-dependent toxicity in developing fish. Environ Toxicol Chem 2018;37:236-246. C 2017 SETAC

The effects of bifenthrin and temperature on the endocrinology of juvenile Chinook salmon

“…Ratios of dopamine and its metabolite 3,4dihydroxyphenylacetic acid have been shown to increase in juvenile zebrafish exposed to bifenthrin (Bertotto et al 2018). Expression of DR2A mRNA was unchanged with bifenthrin exposure in fry at the higher temperature exposures but increased with bifenthrin exposure at 11 8C.…”

“…Rainbow trout become sexually dimorphic at approximately 35 d postfertilization (Vizziano et al 2007), which is comparable to the same alevin stage in Chinook salmon. Life stage has been shown to be important with regard to the estrogenic effects of bifenthrin, with greater estrogenic activity noted in juveniles relative to embryos in zebrafish (Bertotto et al 2018). The gonads in juvenile salmonids are still developing through smoltification; therefore, gonad and HPG development may be more sensitive to stress from temperature compared with older, mature fish.…”

“…The gonads in juvenile salmonids are still developing through smoltification; therefore, gonad and HPG development may be more sensitive to stress from temperature compared with older, mature fish. Life stage has been shown to be important with regard to the estrogenic effects of bifenthrin, with greater estrogenic activity noted in juveniles relative to embryos in zebrafish (Bertotto et al 2018). Temperature increases the rate of development and growth of juvenile salmonids as long as there is ample food availability (Brett et al 1969;Marine and Cech 2004); however, as juvenile fish approach their critical thermal maximum, nutrient conversion and basic physiological processes are impaired (Brett et al 1969).…”

“…In teleost fish, bifenthrin has been shown to affect the dopaminergic pathway, which plays a vital role in the regulation of estrogen homeostasis (Crago and Schlenk 2015;Bertotto et al 2018). Studies with zebrafish have demonstrated that bifenthrin may alter endocrine responses depending on the developmental timing of neuroendocrine pathways in fish (Bertotto et al 2018). The exact mechanism by which bifenthrin affects endocrine pathways in fish is unclear, particularly at different developmental time points.…”

Review of and Recommendations for Monitoring Contaminants and their Effects in the San Francisco Bay−Delta

“…Alkylphenol ethoxylates and alkylphenols APs also enhanced the estrogenic activity of bifenthrin in Fathead Minnow ; however, this interaction's mechanism is unclear. Recent studies in a number of fish species indicate that bifenthrin may alter upstream steroid biosynthesis through dopaminergic and estrogen-receptor signaling , although direct ligand activation of nuclear estrogen receptors (ERs) may not appear to be involved (Bertotto et al 2018). However, the role of bifenthrin metabolites in activating nuclear ERs is still being investigated (DeGroot and Brander 2014).…”