title: Persistent endocrine disruption effects in medaka fish with early life-stage exposure to a triazole-containing aromatase inhibitor (letrozole).
abstract: Letrozole (LET) is a triazole-containing drug that can inhibit the activity of cytochrome P450 aromatase. It is an environmentally emerging pollutant because of its broad use in medicine and frequent occurrence in aquifers receiving the effluent of municipal or hospital wastewater. However, the toxic impact of LET on fish populations remains unclear. We exposed medaka fish (Oryzias latipes) at an early stage of sexual development to a continuous chronic LET at environmentally relevant concentrations and assessed the endocrine disruption effects in adulthood and the next generation. LET exposure at an early life stage persistently altered phenotypic sex development and reproduction in adults and skewed the sex ratio in progeny. As well, LET exposure led to a gender-different endocrine disruption as seen by the interruption in gene expression responsible for estrogen synthesis and metabolism and fish reproduction. LET interfering with the aromatase system in early life stages of medaka can disrupt hormone homeostasis and reproduction. This potent aromatase inhibitor has potential ecotoxicological impact on fish populations in aquatic environments.
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Pei-Han
authors.initials: PH
authors.lastname: Liao
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Szu-Hung
authors.initials: SH
authors.lastname: Chu
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Tu
authors.affiliation: Institute of Environmental Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Xiao-Huan
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Institute of Environmental Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Angela Yu-Chen
authors.initials: AY
authors.lastname: Lin
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan. Electronic address: chenpj@ntu.edu.tw.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D007814:Larva; D000077289:Letrozole; D009570:Nitriles / Q000633:toxicity*; D009990:Oryzias / Q000254:growth & development* / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects; D014230:Triazoles / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D047072:Aromatase Inhibitors; D052244:Endocrine Disruptors; D009570:Nitriles; D014230:Triazoles; D014874:Water Pollutants, Chemical; D000077289:Letrozole
keywords: Aromatase inhibitor; Cytochrome P450 (CYP); Letrozole; Medaka (Oryzias latipes)