Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways J. Soares • L. Filipe C. Castro • M. A. Reis-Henriques • N. M. Monteiro • M. M. Santos Accepted: 5 April 2012 Ó Springer Science+Business Media, LLC 2012 Abstract Parental full life-cycle exposure to ethinylest- radiol (EE 2 ) significantly affects embryo development and survival. One of the possible mechanisms of action of EE 2 may involve the impairment of an organism’s ability to repair DNA damage. DNA repair mechanisms have sophistically evolved to overcome DNA damaging hazards that threaten the integrity of the genome. In the present study, changes in the transcription levels of key genes involved in two of the most thoroughly studied DNA repair systems in mammals were evaluated in adult zebrafish (Danio rerio) gonad upon full life-cycle exposure to chronic environmentally low levels of EE 2 (i.e., 0.5, 1 and 2 ng/L EE 2 ). Real time PCR was used to analyse the expression levels of nucleotide excision repair genes (NER) as well as the tumor suppressor p53 and down- stream selected effectors, i.e., p21 (cyclin-dependent kinase inhibitor), GADD45a (growth arrest and DNA damage induced 45, alpha), bax (bcl2-associated X protein) and p53 key regulator MDM2 (murine double minute 2 protein). NER genes transcription levels in gonads did not differ significantly among treatments. In contrast, the number of transcripts of p53 gene was significantly increased in male gonads at all EE 2 exposure concentra- tions and in females at 1 ng/L EE 2 . Despite the increase in p53 transcripts, transcription levels of p21, GADD45a and bax genes were not affected upon EE 2 treatment, whereas MDM2 gene expression significantly increased in females at the intermediate EE 2 dose (1 ng/L). Overall, the present study indicate that chronic low levels of EE 2 significantly modulates the transcription of p53, a key gene involved in DNA repair, particularly in male zebrafish gonads, which supports the hypothesis of an impact of EE2 in male gonad DNA repair pathways. Keywords Zebrafish Á Ethinylestradiol Á Pharmaceutical Á Embryonic development Á p53 Á NER Á Aneuploidy Á Environmental risk assessment Introduction The aquatic environment is the ultimate recipient of an increasing range of anthropogenic contaminants. Among these, endocrine disrupting chemicals (EDCs) are of major J. Soares Á M. A. Reis-Henriques Á M. M. Santos (&) Laboratory of Environmental Toxicology, CIMAR/CIIMAR- Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Rua dos Bragas 177, 4050-123 Porto, Portugal e-mail: santos@ciimar.up.pt J. Soares ICBAS-Institute of biomedical Sciences Abel Salazar, University of Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto, Portugal L. F. C. Castro Laboratory of Cellular, Molecular and Analytical Studies, CIMAR/CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Rua dos Bragas 177, 4050-123 Porto, Portugal N. M. Monteiro CEBIMED, FCS-UFP, Faculty of Health Sciences, University Fernando Pessoa, Oporto, Portugal N. M. Monteiro CIBIO-Research Centre in Biodiversity and Genetic Resources, Campus Agra ´rio de Vaira ˜o, R. Padre Armando Quintas, 4485-661 Vaira ˜o, Portugal M. M. Santos Department of Biology, Faculty of Sciences, University of Porto (FCUP), Rua do Campo Alegre, 4169-007 Porto, Portugal 123 Ecotoxicology DOI 10.1007/s10646-012-0905-4