title: Reproductive and transcriptional effects of the antiandrogenic progestin chlormadinone acetate in zebrafish (Danio rerio).
abstract: Chlormadinone acetate (CMA) is a frequently used progestin with antiandrogenic activity in humans. Residues may enter the aquatic environment but potential adverse effects in fish are unknown. While our previous work focused on effects of CMA in vitro and in zebrafish eleuthero-embryos, the present study reports on reproductive and transcriptional effects in adult female and male zebrafish (Danio rerio). We performed a reproductive study using breeding groups of zebrafish. After 15 days of pre-exposure, we exposed zebrafish to different measured concentrations between 6.4 and 53,745 ng/L CMA for 21 days and counted produced eggs daily to determine fecundity. Additionally, transcriptional effects of CMA in brains, livers, and gonads were analyzed. CMA induced a slight but statistically significant reduction in fecundity at 65 ng/L and 53,745 ng/L compared to pre-exposure. Furthermore, we observed differential expression for gene transcripts of steroid hormone receptors, genes related to the hypothalamic-pituitary-gonadal axis, and steroidogenesis. In particular, we found a significant decrease of transcript levels of vitellogenin (vtg1) in ovaries and liver, and of cyp2k7 in the liver of males, as well as a significant increase of transcripts of the progesterone receptor (pgr) in testes, and cyp2k1 in the liver of females. The observed effects were weaker than those of other very potent progestins, which is probably related to the lack of interaction of CMA with the zebrafish progesterone receptor.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, FHNW, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Patricia Franziska
authors.initials: PF
authors.lastname: Siegenthaler
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, FHNW, 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, FHNW, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, FHNW, 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. Electronic address: karl.fent@fhnw.ch.
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002715:Chlormadinone Acetate / Q000009:adverse effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000009:adverse effects; D015027:Zebrafish / Q000235:genetics* / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D002715:Chlormadinone Acetate
keywords: Chlormadinone acetate; Endocrine disrupters; Progestins; Reproductive effects; Zebrafish