Manioc : Portail | resultats 1 - 1 pour la recherche: CHEMIX-EST-12-171, ChemPSy-EST-13-081, Institut National de la Santé et de la Recherche Médicale (Inserm).

1 document satisfait la requête. Vérifiez les termes recherchés ou relancez la recherche sur le texte intégral

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants
Auteur(s) : Gaudriault, Pierre Mazaud-Guittot, Séverine Lavoué, Vincent Coiffec, Isabelle Lesné, Laurianne Dejucq-Rainsford, Nathalie Scholze, Martin Kortenkamp, Andreas
Auteurs secondaires : Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Service de Gynécologie et Obstétrique [Rennes] ; Université de Rennes 1 (UR1) - CHU Pontchaillou [Rennes] - Hôpital Sud 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).

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Numerous 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014.
Environmental Health Perspectives

hal-01579609
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579609
DOI : 10.1289/EHP1014
PUBMED : 28796631

| Plus