title: Effects of the estrogen agonist 17beta-estradiol and antagonist tamoxifen in a partial life-cycle assay with zebrafish (Danio rerio).
abstract: A partial life-cycle assay (PLC) with zebrafish (Danio rerio) was conducted to identify endocrine-disrupting effects of 17beta-estradiol (E2) and tamoxifen (TMX) as reference for estrogen agonist and antagonist activity. Adult zebrafish were exposed for 21 d and offspring for another 42 d, allowing differentiation of gonads in control animals. The assessed end points included reproductive variables (egg production, fertilization, and hatching), gonad differentiation of juveniles, histopathology, and vitellogenin (VTG) expression. With E2, the most sensitive end points were feminization of offspring (at 0.1 nM) and increased VTG production in males (at 0.32 nM). At 1 nM, decreased F, survival, increased F, body length and weight, VTG-related edema and kidney lesions, and inhibited spermatogenesis were observed. Oocyte atresia occurred at even higher concentrations. Exposure to TMX resulted in specific effects at an intermediate test concentration (87 nM), including oocyte atresia with granulosa cell transformation and disturbed spermatogenesis (asynchrony within cysts). In F1, decreased hatching, survival, and body weight and length as well as decreased feminization were observed. Decreased vitellogenesis and egg production in females and clustering of Leydig cells in males occurred at higher concentrations. Toxicological profiles of estrogen agonists and antagonists are complex and specific; a valid and refined characterization of endocrine activity of field samples therefore can be obtained only by using a varied set of end points, including histology, as applied in the presented PLC. Evaluation of only a single end point can easily produce under- or overestimation of the actual hazard.
authors.affiliation: Laboratory for Toxicology, Pathology, and Genetics, National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, PO Box 1, Bilthoven NL-3720BA, The Netherlands. l.van.der.ven@rivm.nl
authors.forename: Leo T M
authors.initials: LT
authors.lastname: van der Ven
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: van den Brandhof
authors.forename: José H
authors.initials: JH
authors.lastname: Vos
authors.forename: Piet W
authors.initials: PW
authors.lastname: Wester
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008018:Life Cycle Stages; D008297:Male; D013629:Tamoxifen / Q000494:pharmacology*; D014819:Vitellogenins / Q000378:metabolism; D015027:Zebrafish
chemical_list: D014819:Vitellogenins; D013629:Tamoxifen; D004958:Estradiol