title: Microarray analysis of di-n-butyl phthalate and 17α ethinyl-oestradiol responses in three-spined stickleback testes reveals novel candidate genes for endocrine disruption.
abstract: Phthalate esters are plasticizers frequently found in wastewater effluents. Previous studies on phthalates have reported anti-androgenic activity in mammals, causing concerns of their potential effects on the reproduction of aquatic organisms. Another group of environmental endocrine disrupters, steroidal estrogens, are known to inhibit steroid biosynthesis in the gonads, but the effects related to spermatogenesis are not well understood in fish. In this study, three-spined sticklebacks were exposed to di-n-butyl phthalate (DBP) and 17α ethinyl-oestradiol (EE2) at nominal concentrations 35μg/L and 40ng/L, respectively, for four days. The aim of the study was to obtain insight into the acute transcriptional responses putatively associated with endocrine disruption. RNA samples from eight individual male fish per treatment (including controls) were used in microarray analysis, covering the expression of approximately 21,000 genes. In the EE2 treatment the results show transcriptional downregulation of genes associated with steroid biosynthesis pathway and up-regulation of genes involved in pathways related to epidermal growth factor signaling and xenobiotic metabolism. The transcriptional response to DBP was in general weaker than to EE2, but based on enrichment analysis, we suggest adverse effects on retinoid metabolism, creatine kinase activity and cell adhesion. Among the genes showing highest fold changes after DBP treatment compared to control was the teleost fish -specific cytochrome P450 17A2. Overall, this study promotes our understanding on molecular responses to anti-androgens and estrogens in fish testes.
authors.affiliation: Department of Biology, University of Turku, 20014 Turku, Finland. Electronic address: jmprok@utu.fi.
authors.forename: Jenni M
authors.initials: JM
authors.lastname: Prokkola
authors.affiliation: Centre for Environment, Fisheries and Aquaculture Science, Weymouth, UK.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Katsiadaki
authors.affiliation: Centre for Environment, Fisheries and Aquaculture Science, Weymouth, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Sebire
authors.affiliation: Centre for Environment, Fisheries and Aquaculture Science, Weymouth, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Elphinstone-Davis
authors.affiliation: Department of Biology, University of Turku, 20014 Turku, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Pausio
authors.affiliation: Department of Biology, University of Turku, 20014 Turku, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Nikinmaa
authors.affiliation: Department of Biology, University of Turku, 20014 Turku, Finland; Natural History Museum, University of Oslo, Oslo NO-0318, Norway.
authors.forename: Erica H
authors.initials: EH
authors.lastname: Leder
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity; D000818:Animals; D003993:Dibutyl Phthalate / Q000633:toxicity*; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D046228:Microarray Analysis; D010968:Plasticizers / Q000633:toxicity*; D023701:Smegmamorpha / Q000235:genetics*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D004967:Estrogens; D010968:Plasticizers; D014874:Water Pollutants, Chemical; D003993:Dibutyl Phthalate; D004997:Ethinyl Estradiol
keywords: Endocrine disruption; Gonads; Reproduction; Spermatogenesis; Transcriptomics