title: Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio).
abstract: Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhao
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 (ETH Zürich), Institute of Biogeochemistry and Pollution Dynamics, Department of Environmental System Sciences, CH-8092 Zürich, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000736:Androstenes / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D052244:Endocrine Disruptors / Q000633:toxicity; D005123:Eye / Q000187:drug effects / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006066:Gonads / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000096:biosynthesis
chemical_list: D000736:Androstenes; D052244:Endocrine Disruptors; D011372:Progestins; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D011374:Progesterone; C035144:drospirenone