title: Effects of low concentrations of the antiprogestin mifepristone (RU486) in adults and embryos of zebrafish (Danio rerio): 1. Reproductive and early developmental effects.
abstract: Effects of synthetic progestins have recently been reported in fish, but potential effects of the synthetic antiprogestin mifepristone (MIF), also called RU486, have not been studied. The present study provides first insights into reproductive effects of MIF in zebrafish in comparison to the progesterone receptor agonist, progesterone (P4). We carried out a reproductive study using breeding groups of adult zebrafish. After a 14 day pre-exposure, zebrafish were exposed for 21 days to 5, 39, 77 ng/L MIF, 25 ng/L P4 and water and solvent controls. In addition, embryos originating from exposed adult fish were continuously exposed to 3, 15, 26 ng/L MIF, and 254 ng/L P4, respectively, for 96 h post fertilization. We found a significant U-shaped increase in egg production after exposure to 5 and 77 ng/L MIF, but no effects at 25 ng/L P4. Levels of sex steroid hormones in blood plasma of adult males (11-ketotestosterone) and females (17 β-estradiol) were not altered. In addition to an increase of mature vitellogenic oocytes in ovaries of females exposed to MIF and P4, we observed several histopathological changes in ovaries, including post-ovulatory follicles, atretic follicles and proteinaceous fluid. Male gonads showed no or less alterations and no histopathological effects. Fertility of eggs and hatching success of embryos (F1 generation) was not affected at 3-26 ng/L MIF and 254 ng/L P4, respectively. The data lead to the conclusion that trace quantities of MIF affect reproduction of zebrafish and ovaries of female zebrafish. Effects on transcriptional changes in adult and embryonic zebrafish of this study in comparison to in vitro effects are reported in the associated report (Blüthgen et al., 2013a).
authors.affiliation: University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Institute for Ecopreneurship, Gründenstrasse 40, 4132 Muttenz, Switzerland; University of Basel, Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Blüthgen
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006066:Gonads / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones; D014874:Water Pollutants, Chemical; D015735:Mifepristone
keywords: Antiprogestin; Mifepristone; Progesterone; RU486; Reproductive effects