An integrated transcriptomic and proteomic approach characterizing estrogenic and metabolic effects of 17 alpha-ethinylestradiol in zebrafish (Danio rerio).
Nowadays there is much concern about the presence of endocrine disrupting compounds (EDCs) in the environment due to their ability to interfere with the endocrine system. In the presented study, adult zebrafish (Danio rerio) were exposed to 30 ng L(-1) 17alpha-ethinylestradiol (EE2) for 4 and 28 days. The underlying molecular mechanisms of EE2 were studied in the zebrafish liver by applying a combined transcriptomics and proteomics approach. In addition, we assessed the added value of such an integrated-omics approach. Oligo microarrays, spotted with 3479 zebrafish-specific oligos, were employed to generate differential gene expression levels. The proteomic responses were evaluated by means of differential in-gel electrophoresis (DiGE), combined with MALDI-tandem mass spectrometry. Assessment of the major biological functions of the differentially expressed transcripts and proteins illustrated that both individual platforms could profile a clear estrogenic interference, next to numerous metabolism-related effects and stress responses. Cross-comparison of both transcriptomics and proteomics datasets displayed limited concordance, though, thorough revision of the results illustrated that transcriptional effects were projected on protein level as downstream effects of affected signalling pathways. Overall, this study demonstrated that a proteomics approach can lift the biological interpretation of microarrays to a higher level, and moreover, opens a window for identification of possible new biomarkers.
Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Marijke.dewit@ua.ac.be
Marijke
M
De Wit
Dorien
D
Keil
Karlijn
K
van der Ven
Stefaan
S
Vandamme
Erwin
E
Witters
Wim
W
De Coen
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics
D052244:Endocrine Disruptors; D004967:Estrogens; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D004997:Ethinyl Estradiol