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dc.contributor.authorGaudriault, P-
dc.contributor.authorMazaud-Guittot, S-
dc.contributor.authorLavoué, V-
dc.contributor.authorCoiffec, I-
dc.contributor.authorLesné, L-
dc.contributor.authorDejucq-Rainsford, N-
dc.contributor.authorScholze, M-
dc.contributor.authorKortenkamp, A-
dc.contributor.authorJégou, B-
dc.identifier.citationEnvironmental Health Perspectives, 2017, 125 (8)en_US
dc.description.abstractNumerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.en_US
dc.description.sponsorshipWe thank all the staff of the Department of Obstetrics and Gynecology and the Department of Pediatric Surgery of the Rennes Sud Hospital (Rennes, France) and the participating women, without whom this study would not have been possible. We acknowledge the financial supports from the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES) ; CHEMIX-EST-12-171, ChemPSy- EST-13-081, Institut National de la Santé et de la Recherche Médicale (Inserm). P.Gaudriault is a recipient of a stipend of the Fondation pour la Recherche Médicale.en_US
dc.titleEndocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutantsen_US
dc.relation.isPartOfEnvironmental Health Perspectives-
Appears in Collections:Dept of Clinical Sciences Research Papers

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