title: Tissue-, sex- and development-specific transcription profiles of eight UDP-glucuronosyltransferase genes in zebrafish (Danio rerio) and their regulation by activator of aryl hydrocarbon receptor.
abstract: UDP-Glucuronosyltransferases (Ugts) are phase II biotransformation enzymes that glucuronidate numerous endogenous and xenobiotic substrates. Based on the reported zebrafish Ugt gene repertoire, primers for the Ugt1a and Ugt1b family and for individual Ugt5a1, Ugt5a3, Ugt5a4, Ugt5a5, Ugt5c2 and Ugt5c3 were designed and applied in RT-qPCR analyses. Transcriptional expression profiles of these Ugts were analyzed in intestine, liver, gonad and brain of female and male adult zebrafish and at different embryonic developmental stages. We found tissue-, sex- and developmental-specific expression patterns for all isoforms. Throughout all tissues, the most abundant Ugts were Ugt1a, Ugt1b, Ugt5a1 and Ugt5a3. Expression during embryonic development was assessed between 24 and 120 hpf. Ugts showed a development-dependent expression. The pattern of Ugt1a, Ugt1b, Ugt5a1, Ugt5a3 and Ugt5a4 were similar with highest expression at 24 hpf followed by a decrease and rebound increase up to 120 hpf. To analyze for transcriptional regulation of Ugts by the arylhydrocarbon receptor (ahr2), zebrafish eleuthero-embryos were exposed to 5, 25 and 50μg/L benzo(a)pyrene (BaP), a model ahr2 regulator for cyp1a. Besides transcriptional induction of ahr2 and cyp1a, BaP produced a significant induction of Ugt1a, Ugt5a1, Ugt5a3 and Ugt5a5 as well as a down-regulation of Ugt1b. These data demonstrate the link between ahr2 signalling and transcriptional expression of Ugt genes. This is the first study showing transcriptional expression of eight different Ugts in tissues and during embryonic development and offers new perspectives on the involvement of Ugts in fish xenobiotic metabolism.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Christen
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland; Swiss Federal Institute of Technology Zürich (ETH Zürich), Institute of Biogeochemistry and Pollution Dynamics, Environmental Systems Science, 8092 Zürich, Switzerland. Electronic address: karl.fent@fhnw.ch.
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002460:Cell Line; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012737:Sex Factors; D059467:Transcriptome; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D001564:Benzo(a)pyrene; D014453:Glucuronosyltransferase; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D000099148:UGT1A1 Enzyme
keywords: Aryl hydrocarbon receptor; Developmental expression; Phase II enzymes; Transcription profile; UDP-Glucuronosyltransferases; Ugt; Zebrafish