title: Gonadal transcriptome responses and physiological consequences of exposure to oestrogen in breeding zebrafish (Danio rerio).
abstract: Environmental oestrogens are widespread in the aquatic environment and cause alterations in sexual development and function in vertebrates. The molecular pathways underpinning these effects, however, remain poorly understood. In this study, we aimed at generating a mechanistic understanding of the disruptive effects of exposure to environmentally relevant concentrations of 17 alpha-ethinyloestradiol (EE(2)) on reproduction in zebrafish, by anchoring the transcriptomic alterations induced with the physiological consequences of exposure. Breeding colonies of zebrafish were exposed for a 21-day period to three concentrations of EE(2) (0.05, 0.5 and 5 ng/L) and the gonadal transcriptomic alterations induced (determined using a 17,000 oligonucleotide microarray) were analysed together with physiological effects seen on reproductive output of both males and females. Exposure to 5 ng EE(2)/L resulted in reproductive impairment characterised by a decrease in egg production, alterations in sperm quality and reduced fertilisation success. The effects seen were associated with altered expression of 114 and 131 genes in the gonads of males and females, respectively. The biological processes most affected by the exposure were protein metabolism in males and mitochondria organisation and biogenesis in females. Genes involved in the regulation of cell cycle progression, the ubiquitin system and glutathione peroxidase were affected by the EE(2) exposure and associated with the changes observed in gamete quality in both genders. In summary, we demonstrated that EE(2) exposure compromised the reproductive health of breeding zebrafish at environmentally relevant concentrations. The molecular mechanisms mediating some of these effects were identified and included those impacting processes central to gametogenesis in both males and females.
authors.affiliation: School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, UK. E.Santos@exeter.ac.uk <E.Santos@exeter.ac.uk>
authors.forename: Eduarda M
authors.initials: EM
authors.lastname: Santos
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Paull
authors.forename: Katrien J W
authors.initials: KJ
authors.lastname: Van Look
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Workman
authors.forename: William V
authors.initials: WV
authors.lastname: Holt
authors.forename: Ronny
authors.initials: R
authors.lastname: van Aerle
authors.forename: Peter
authors.initials: P
authors.lastname: Kille
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004781:Environmental Exposure; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005306:Fertilization / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005796:Genes / Q000187:drug effects / Q000502:physiology; D006066:Gonads / Q000187:drug effects*; D008297:Male; D009866:Oogenesis / Q000187:drug effects; D010641:Phenotype; D025341:Principal Component Analysis; D013094:Spermatozoa / Q000187:drug effects; D014867:Water / Q000032:analysis; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D014867:Water; D004997:Ethinyl Estradiol