title: Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish.
abstract: 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 48hpf (hours post-fertilization) embryos than in the 24hpf embryos. While 24hpf embryos were non-responsive in this regard to 25μM nicotine, a similar exposure of the 48hpf embryos for 24h significantly down-regulated the expression of all four ED biomarker genes indicating that nicotine's anti-estrogenic effects are detectable in the 48hpf zebrafish embryos. These results provide direct molecular evidence that nicotine is an endocrine disruptor in zebrafish.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. jyotshnabala.kanungo@fda.hhs.gov
authors.forename: Jyotshna
authors.initials: J
authors.lastname: Kanungo
authors.forename: Elvis
authors.initials: E
authors.lastname: Cuevas
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guo
authors.forename: Aida G
authors.initials: AG
authors.lastname: Lopez
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Ramirez-Lee
authors.forename: William
authors.initials: W
authors.lastname: Trickler
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D009538:Nicotine / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D004967:Estrogens; D014819:Vitellogenins; D029961:Zebrafish Proteins; D004958:Estradiol; D009538:Nicotine; D001141:Aromatase; C440729:Cyp19a1a protein, zebrafish; C440728:Cyp19a1b protein, zebrafish