TY - JOUR
T1 - Environmentally-relevant mixture of pharmaceutical drugs stimulates sex-steroid hormone production and modulates the expression of candidate genes in the ovary of juvenile female rainbow trout
AU - Schmitz, Mélodie
AU - Beghin, Mahaut
AU - Mandiki, Robert
AU - Nott, Katherine
AU - Gillet, Michaël
AU - Ronkart, Sébastien
AU - Robert, Christelle
AU - Baekelandt, Sébastien
AU - Kestemont, Patrick
N1 - Funding Information:
This work was carried out in the framework of the Project DIADEM (Développement d’une Approche Intégrée pour le Diagnostic de la qualité des Eaux de la Meuse) and was supported by the Interreg France-Wallonia-Vlaanderen (European Union) and the Public Service of Wallonia . Thanks are also due to the scientific and technical staff of the Research Unit in Environmental and Evolutionary Biology (URBE) of the University of Namur for their support during fish organ sampling.
Publisher Copyright:
© 2018 Elsevier B.V.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Because of their intrinsic biological activity and ubiquitous environmental occurrence, human pharmaceutical compounds have received increasing attention from health and environmental agencies. In the present study, all-female juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally-realistic concentrations of a mixture of nonsteroidal pharmaceuticals for 42 days, and the effects on plasma levels of sex-steroids and the expression of genes encoding key proteins involved in ovarian development were assessed. Paracetamol, carbamazepine, diclofenac, irbesartan and naproxen were selected, as these have been detected in the Meuse River in Belgium. Fish were exposed to three concentrations of the mixture including the environmental concentration, 10- and 100-times the environmental concentration. Plasma levels of sex-steroid hormones, particularly 11-ketotestosterone, increased in a concentration-dependent way in exposed females. In addition, some key genes involved in ovarian steroidogenesis were significantly overexpressed after 7 days of exposure, such as key genes involved in the maintenance of the ovary. The steady-state mRNA level of genes implicated in germ cell fate were especially affected, such as that of foxl3 which increased by 5 fold at the highest concentration of the mixture. In conclusion, this study highlights that combined occurrence of common pharmaceutical drugs at concentrations present in surface water environments may act as endocrine-disrupting compounds in rainbow trout.
AB - Because of their intrinsic biological activity and ubiquitous environmental occurrence, human pharmaceutical compounds have received increasing attention from health and environmental agencies. In the present study, all-female juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally-realistic concentrations of a mixture of nonsteroidal pharmaceuticals for 42 days, and the effects on plasma levels of sex-steroids and the expression of genes encoding key proteins involved in ovarian development were assessed. Paracetamol, carbamazepine, diclofenac, irbesartan and naproxen were selected, as these have been detected in the Meuse River in Belgium. Fish were exposed to three concentrations of the mixture including the environmental concentration, 10- and 100-times the environmental concentration. Plasma levels of sex-steroid hormones, particularly 11-ketotestosterone, increased in a concentration-dependent way in exposed females. In addition, some key genes involved in ovarian steroidogenesis were significantly overexpressed after 7 days of exposure, such as key genes involved in the maintenance of the ovary. The steady-state mRNA level of genes implicated in germ cell fate were especially affected, such as that of foxl3 which increased by 5 fold at the highest concentration of the mixture. In conclusion, this study highlights that combined occurrence of common pharmaceutical drugs at concentrations present in surface water environments may act as endocrine-disrupting compounds in rainbow trout.
KW - Endocrine-disrupting compounds
KW - Pharmaceutical drugs
KW - Rainbow trout
KW - Reproduction
KW - Acetaminophen/toxicity
KW - Carbamazepine/toxicity
KW - Diclofenac/toxicity
KW - Endocrine Disruptors/toxicity
KW - Testosterone/analogs & derivatives
KW - Ovary/drug effects
KW - Irbesartan/toxicity
KW - Naproxen/toxicity
KW - Oncorhynchus mykiss/blood
KW - Animals
KW - Belgium
KW - Water Pollutants, Chemical/toxicity
KW - Female
KW - Gonadal Steroid Hormones/blood
KW - Gene Expression Regulation/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85055054104&partnerID=8YFLogxK
U2 - 10.1016/j.aquatox.2018.10.006
DO - 10.1016/j.aquatox.2018.10.006
M3 - Article
C2 - 30347285
AN - SCOPUS:85055054104
SN - 0166-445X
VL - 205
SP - 89
EP - 99
JO - Aquatic Toxicology
JF - Aquatic Toxicology
ER -