Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.

Institut National de l'Environnement Industriel et des Risques Unité d'Ecotoxicologie in vitro et in vivo UMR 1 02 SEBIO Verneuil en Halatte France

University of South Bohemia in České Budějovice Faculty of Fisheries and Protection of Waters Vodňany Czech Republic

University of South Bohemia in České Budějovice Faculty of Fisheries and Protection of Waters Vodňany Czech Republic; Department of Aquatic Sciences and Assessment Swedish University of Agricultural Sciences Box 7050 SE 750 07 Uppsala Sweden

Wageningen University Animal Breeding and Genomics Centre Wageningen the Netherlands

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