title: Meta-Analysis of Microarray Data of Rainbow Trout Fry Gonad Differentiation Modulated by Ethynylestradiol.
abstract: Sex differentiation in fish is a highly labile process easily reversed by the use of exogenous hormonal treatment and has led to environmental concerns since low doses of estrogenic molecules can adversely impact fish reproduction. The goal of this study was to identify pathways altered by treatment with ethynylestradiol (EE2) in developing fish and to find new target genes to be tested further for their possible role in male-to-female sex transdifferentiation. To this end, we have successfully adapted a previously developed bioinformatics workflow to a meta-analysis of two datasets studying sex reversal following exposure to EE2 in juvenile rainbow trout. The meta-analysis consisted of retrieving the intersection of the top gene lists generated for both datasets, performed at different levels of stringency. The intersecting gene lists, enriched in true positive differentially expressed genes (DEGs), were subjected to over-representation analysis (ORA) which allowed identifying several statistically significant enriched pathways altered by EE2 treatment and several new candidate pathways, such as progesterone-mediated oocyte maturation and PPAR signalling. Moreover, several relevant key genes potentially implicated in the early transdifferentiation process were selected. Altogether, the results show that EE2 has a great effect on gene expression in juvenile rainbow trout. The feminization process seems to result from the altered transcription of genes implicated in normal female gonad differentiation, resulting in expression similar to that observed in normal females (i.e. the repression of key testicular markers cyp17a1, cyp11b, tbx1), as well as from other genes (including transcription factors) that respond specifically to the EE2 treatment. The results also showed that the bioinformatics workflow can be applied to different types of microarray platforms and could be generalized to (eco)toxicogenomics studies for environmental risk assessment purposes.
authors.affiliation: University of Namur (UNamur), Research Unit in Environmental and Evolutionary Biology (URBE-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Depiereux
authors.affiliation: Institut National de la Recherche Agronomique, INRA-LPGP, UPR1037, Campus de Beaulieu, 35042, Rennes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Le Gac
authors.affiliation: University of Namur (UNamur), Research Unit in Molecular Biology (URBM-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: De Meulder
authors.affiliation: University of Namur (UNamur), Research Unit in Molecular Biology (URBM-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Pierre
authors.affiliation: University of Namur (UNamur), Research Unit in Molecular Biology (URBM-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Helaers
authors.affiliation: Institut National de la Recherche Agronomique, INRA-LPGP, UPR1037, Campus de Beaulieu, 35042, Rennes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Guiguen
authors.affiliation: University of Namur (UNamur), Research Unit in Environmental and Evolutionary Biology (URBE-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kestemont
authors.affiliation: University of Namur (UNamur), Research Unit in Molecular Biology (URBM-NARILIS), 61 rue de Bruxelles, B-5000, Namur, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Depiereux
mesh_terms: D000818:Animals; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D006066:Gonads / Q000187:drug effects* / Q000254:growth & development*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017686:Oncorhynchus mykiss / Q000235:genetics* / Q000254:growth & development*; D012733:Sex Differentiation / Q000187:drug effects* / Q000235:genetics
chemical_list: D004997:Ethinyl Estradiol