title: Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish.
abstract: This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea; Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Department of Occupational and Environmental Health, Yongin University, Yongin 449-714, Republic of Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Ji
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Saeram
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kang
authors.affiliation: School of Human & Environmental Sciences, Eulji University, Seongnam 461-713, Republic of Korea.
authors.forename: Younglim
authors.initials: Y
authors.lastname: Kho
authors.affiliation: Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: kyungho@snu.ac.kr.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D006066:Gonads / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012098:Reproduction / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical; D013739:Testosterone; D004958:Estradiol