Reversibility of endocrine disruption in zebrafish (Danio rerio) after discontinued exposure to the estrogen 17α-ethinylestradiol.
The aim of the present study was to investigate the persistence of the feminizing effects of discontinued 17α-ethinylestradiol (EE2) exposure on zebrafish (Danio rerio). An exposure scenario covering the sensitive phase of sexual differentiation, as well as final gonad maturation was chosen to examine the estrogenic effects on sexual development of zebrafish. Two exposure scenarios were compared: continuous exposure to environmentally relevant concentrations (0.1-10 ng/L EE2) up to 100 days post-hatch (dph) and developmental exposure up to 60 dph, followed by 40 days of depuration in clean water. The persistence of effects was investigated at different biological organization levels from mRNA to population-relevant endpoints to cover a broad range of important parameters. EE2 had a strong feminizing and inhibiting effect on the sexual development of zebrafish. Brain aromatase (cyp19b) mRNA expression showed no clear response, but vitellogenin levels were significantly elevated, gonad maturation and body growth were inhibited in both genders, and sex ratios were skewed towards females and undifferentiated individuals. To a large extent, all of these effects were reversed after 40 days of recovery, leading to the conclusion that exposure to the estrogen EE2 results in very strong, but reversible underdevelopment and feminization of zebrafish. The present study is the first to show this reversibility at different levels of organization, which gives better insight into the mechanistic basis of estrogenic effects in zebrafish.
Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Bern, PO Box 8466, CH-3001 Bern, Switzerland; Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: lisa.baumann@vetsuisse.unibe.ch.
Lisa
L
Baumann
Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: susanne.knoerr@gmx.de.
Susanne
S
Knörr
Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: susanne.keiter@cos.uni-heidelberg.de.
Susanne
S
Keiter
Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: k.rehberger@stud.uni-heidelberg.de.
Kristina
K
Rehberger
Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: s.volz@stud.uni-heidelberg.de.
Sina
S
Volz
Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, D-52074 Aachen, Germany. Electronic address: schiller@molbiotech.rwth-aachen.de.
Viktoria
V
Schiller
Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, D-52074 Aachen, Germany. Electronic address: martina.fenske@ime.fraunhofer.de.
Martina
M
Fenske
Department of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. Electronic address: hol@biology.sdu.dk.
Henrik
H
Holbech
Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Bern, PO Box 8466, CH-3001 Bern, Switzerland. Electronic address: helmut.segner@vetsuisse.unibe.ch.
Helmut
H
Segner
Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. Electronic address: braunbeck@uni-hd.de.
Thomas
T
Braunbeck
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049628:Body Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D052918:Environmental Restoration and Remediation; D004967:Estrogens / Q000008:administration & dosage / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005262:Feminization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D009928:Organ Specificity; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012733:Sex Differentiation / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D052244:Endocrine Disruptors; D004967:Estrogens; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C486450:vtg1 protein, zebrafish; D004997:Ethinyl Estradiol
Aromatase; Endocrine disruptor; Estrogen; Gonad histology; Sexual differentiation; Vitellogenin