title: An investigation of the endocrine-disruptive effects of bisphenol a in human and rat fetal testes.
abstract: Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10(-8)M and 10(-5)M for 72 h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48 h in both strains. BPA at 10(-7)-10(-5)M for 72 h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10(-8)M, 10(-7)M, and 10(-5)M for 72 h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Millissia
authors.initials: M
authors.lastname: Ben Maamar
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Laurianne
authors.initials: L
authors.lastname: Lesné
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Desdoits-Lethimonier
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coiffec
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lassurguère
authors.affiliation: CHU Rennes, Service Gynécologie et Obstétrique, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lavoué
authors.affiliation: USC 1329 LABERCA, ONIRIS, Atlanpôle-La Chantrerie, Nantes, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Deceuninck
authors.affiliation: USC 1329 LABERCA, ONIRIS, Atlanpôle-La Chantrerie, Nantes, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Antignac
authors.affiliation: USC 1329 LABERCA, ONIRIS, Atlanpôle-La Chantrerie, Nantes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Le Bizec
authors.affiliation: UMR 1331 TOXALIM, INRA (Institut National de la Recherche Agronomique), Chemin de Tournefeuille, Toulouse, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perdu
authors.affiliation: UMR 1331 TOXALIM, INRA (Institut National de la Recherche Agronomique), Chemin de Tournefeuille, Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zalko
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Pineau
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Chevrier
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dejucq-Rainsford
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Mazaud-Guittot
authors.affiliation: Inserm (Institut national de la santé et de la recherche médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, Rennes, CEDEX, France; Université de Rennes I, Campus de Beaulieu, Rennes, CEDEX, France; EHESP-School of Public Health, Avenue du Professeur Léon Bernard, Rennes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000196:embryology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds