Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

Abstract : Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10(-9)-10(-5) M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10(-9) M; P < 0.05), BPB (10(-9) M; P < 0.05), BPS (10(-9) and 10(-8) M; P < 0.05) and BADGE (10(-5) M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.
Type de document :
Article dans une revue
Human Reproduction, Oxford University Press (OUP), 2017, 32 (7), pp.1465--1473. 〈10.1093/humrep/dex093〉
Liste complète des métadonnées

Littérature citée [17 références]  Voir  Masquer  Télécharger

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582
Contributeur : Laurent Jonchère <>
Soumis le : mardi 24 octobre 2017 - 11:37:58
Dernière modification le : jeudi 21 décembre 2017 - 13:28:03

Fichier

Parallel assessment of the eff...
Fichiers produits par l'(les) auteur(s)

Identifiants

Citation

Christèle Desdoits-Lethimonier, Lauriane Lesné, Pierre Gaudriault, Daniel Zalko, Jean-Philippe Antignac, et al.. Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis. Human Reproduction, Oxford University Press (OUP), 2017, 32 (7), pp.1465--1473. 〈10.1093/humrep/dex093〉. 〈hal-01578582〉

Partager

Métriques

Consultations de la notice

114

Téléchargements de fichiers

16