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Effect of in vivo chronic exposure to clotrimazole on zebrafish testis function.
MedLine Citation:
PMID:  23340899     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Clotrimazole is an azole fungicide used as a human pharmaceutical that is known to inhibit cytochrome P450 (CYP) enzymatic activities, including several steroidogenic CYP. In a previous report, we showed that a 7-day exposure to clotrimazole induced the expression of genes related to steroidogenesis in the testes as a compensatory response, involving the activation of the Fsh/Fshr pathway. In this context, the aim of the present study was to assess the effect of an in vivo 21-day chronic exposure to clotrimazole (30-197 μg/L) on zebrafish testis function, i.e., spermatogenesis and androgen release. The experimental design combined (1) gene transcript levels measurements along the brain-pituitary-gonad axis, (2) 11-ketotestosterone (11-KT) quantification in the blood, and (3) histology of the testes, including morphometric analysis. The chronic exposure led to an induction of steroidogenesis-related genes and fshr in the testes as well as fshβ in the pituitary. Moreover, increases of the gonadosomatic index and of the volume proportion of interstitial Leydig cells were observed in clotrimazole-exposed fish. In accordance with these histological observations, the circulating concentration of 11-KT had increased. Morphometric analysis of the testes did not show an effect of clotrimazole on meiotic (spermatocytes) or postmeiotic (spermatids and spermatozoa) stages, but we observed an increase in the number of type A spermatogonia, in agreement with an increase in mRNA levels of piwil1, a specific molecular marker of type A spermatogonia. Our study demonstrated that clotrimazole is able to affect testicular physiology and raised further concern about the impact of clotrimazole on reproduction.
Authors:
Damien Baudiffier; Nathalie Hinfray; Catherine Ravaud; Nicolas Creusot; Edith Chadili; Jean-Marc Porcher; Rüdiger W Schulz; François Brion
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Environmental science and pollution research international     Volume:  -     ISSN:  1614-7499     ISO Abbreviation:  Environ Sci Pollut Res Int     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9441769     Medline TA:  Environ Sci Pollut Res Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Direction des Risques Chroniques, Pôle VIVA, Unité d'écotoxicologie in vitro et in vivo, INERIS, Parc Technologique Alata, BP2, 60550, Verneuil-en-Halatte, France.
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