Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish

Nicotine, a drug of abuse, has been reported to have many adverse effects on the developing nervous system. In rodents, chronic nicotine exposure inhibits estrogen-mediated neuroprotection against cerebral ischemia in females suggesting that nicotine could disrupt endocrine targets. Zebrafish have been used as a model system for examining mechanisms underlying nicotinic effects on neuronal development. Here, using zebrafish embryos, we demonstrate that nicotine alters the expression of the validated endocrine disruption (ED) biomarkers, vitellogenin (vtg 1 and vtg 2) and cytochrome p450 aromatase (cyp19a1a and cyp19a1b) at the transcriptional level. Increased expression of three of these molecular markers (vtg 1, vtg 2 and cyp19a1b) in response to 17β-estradiol (E2) was more pronounced in 48 hpf (hours post-fertilization) embryos than in the 24 hpf embryos. While 24 hpf embryos were non-responsive in this regard to 25 μM nicotine, a similar exposure of the 48 hpf embryos for 24 h significantly down-regulated the expression of all four ED biomarker genes indicating that nicotine's anti-estrogenic effects are detectable in the 48 hpf zebrafish embryos. These results provide direct molecular evidence that nicotine is an endocrine disruptor in zebrafish.

► 17β-Estradiol induces Vtg1/2 and Cyp19a1b expression but not Cyp19a1a in zebrafish. ► Nicotine down regulates ED biomarkers, Vtg1/2 expression in zebrafish. ► Nicotine down regulates ED biomarkers, Cyp19a1a and Cyp19a1b expression in zebrafish.