title: Hepatic transcriptomic and metabolomic responses in the Stickleback (Gasterosteus aculeatus) exposed to ethinyl-estradiol.
abstract: An established three-spined stickleback (Gasterosteus aculeatus) cDNA array was expanded to 14,496 probes with the addition of hepatic clones derived from subtractive and normalized libraries from control males and males exposed to model toxicants. Microarrays and one-dimensional (1)H nuclear magnetic resonance (NMR) spectroscopy, together with individual protein and gene biomarkers were employed to investigate the hepatic responses of the stickleback to ethinyl-estradiol (EE(2)) exposure. Male fish were exposed via the water to EE(2), including environmentally relevant concentrations (0.1-100ng/l) for 4 days, and hepatic transcript and metabolite profiles, kidney spiggin protein and serum vitellogenin concentrations were determined in comparison to controls. EE(2) exposure did not significantly affect spiggin concentration but significantly induced serum vitellogenin protein at the threshold concentration of 32ng/l. (1)H NMR coupled with robust univariate testing revealed only limited changes, but these did support the predicted modulation of the amino acid profile by transcriptomics. Transcriptional induction was found for hepatic vitellogenins and choriogenins as expected, together with a range of other EE(2)-responsive genes. Choriogenins showed the more sensitive responses with statistically significant induction at 10ng/l. Real-time polymerase chain reaction (PCR) confirmed transcriptional induction of these genes. Phosvitinless vitellogenin C transcripts were highly expressed and represent a major form of the egg yolk precursors, and this is in contrast to other fish species where it is a minor component of vitellogenic transcripts. Differences in inducibility between the vitellogenins and choriogenins appear to be in accordance with the sequential formation of chorion and yolk during oogenesis in fish.
authors: Centre for Environment, Fisheries and Aquaculture Science, Cefas Weymouth Laboratory, Weymouth, Dorset, UK. ioanna.katsiadaki@cefas.co.uk
authors: Ioanna
authors: I
authors: Katsiadaki
authors: Tim D
authors: TD
authors: Williams
authors: Jonathan S
authors: JS
authors: Ball
authors: Tim P
authors: TP
authors: Bean
authors: Matthew B
authors: MB
authors: Sanders
authors: Huifeng
authors: H
authors: Wu
authors: Eduarda M
authors: EM
authors: Santos
authors: Margaret M
authors: MM
authors: Brown
authors: Paul
authors: P
authors: Baker
authors: Fernando
authors: F
authors: Ortega
authors: Francesco
authors: F
authors: Falciani
authors: John A
authors: JA
authors: Craft
authors: Charles R
authors: CR
authors: Tyler
authors: Mark R
authors: MR
authors: Viant
authors: James K
authors: JK
authors: Chipman
mesh_terms: D000818:Animals; D015415:Biomarkers; D052244:Endocrine Disruptors / Q000633:toxicity; D004997:Ethinyl Estradiol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D023701:Smegmamorpha / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical; D004997:Ethinyl Estradiol