title: Transcriptional and morphological effects of tamoxifen on the early development of zebrafish (Danio rerio).
abstract: Tamoxifen is a widely used anticancer drug with both an estrogen agonist and antagonist effect. This study focused on its endocrine disrupting effect, and overall environmental significance. Zebrafish embryos were exposed to different concentrations (0.5, 5, 50 and 500 µg l(-1) ) of tamoxifen for 96 h. The results showed a complex effect of tamoxifen on zebrafish embryo development. For the 500 µg l(-1) exposure group, the heart rate was decreased by 20% and mild defects in caudal fin and skin were observed. Expressions of a series of genes related to endocrine and morphological changes were subsequently tested through quantitative real-time polymerase chain reaction. Bisphenol A as a known estrogen was also tested as an endocrine-related comparison. Among the expression of endocrine-related genes, esr1, ar, cyp19a1b, hsd3b1 and ugt1a1 were all increased by tamoxifen exposure, similar to bisphenol A. The cyp19a1b is a key gene that controls estrogen synthesis. Exposure to 0.5, 5, 50 and 500 µg l(-1) of tamoxifen caused upregulation of cyp19a1b expression to 152%, 568%, 953% and 2024% compared to controls, higher than the effects from the same concentrations of bisphenol A treatment, yet vtg1 was suppressed by 24% from exposure to 500 µg l(-1) tamoxifen. The expression of metabolic-related genes such as cyp1a, cyp1c2, cyp3a65, gpx1a, gstp1, gsr and genes related to observed morphological changes such as krt17 were also found to be upregulated by high concentrations of tamoxifen. These findings indicated the potential environmental effect of tamoxifen on teleost early development. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan North Road, Shanghai, 200062, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan North Road, Shanghai, 200062, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 Zhongshan North Road, Shanghai, 200062, China.
authors.forename: Jun Liang
authors.initials: JL
authors.lastname: Zhou
mesh_terms: D058500:Animal Fins / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009994:Osmolar Concentration; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000196:embryology; D012868:Skin Abnormalities / Q000139:chemically induced / Q000196:embryology / Q000662:veterinary; D013629:Tamoxifen / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity; D014819:Vitellogenins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D020845:Selective Estrogen Receptor Modulators; D013723:Teratogens; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C486450:vtg1 protein, zebrafish; D013629:Tamoxifen; D001141:Aromatase; C440728:Cyp19a1b protein, zebrafish
keywords: Developmental toxicity; Endocrine disrupting chemicals; Gene expression; Tamoxifen; Zebrafish embryos