title: Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice.
abstract: There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)7224 (M.P., L.N., C.M.-L., K.R., V.G.-M., S.M.-K.), Inserm 952 (M.P., L.N., C.M.-L., K.R., V.G.-M., S.M.-K.), and Physiopathologie des Maladies du Système Nerveux Central (M.P., L.N., C.M.-L., K.R., V.G.-M., S.M.-K.), Université Pierre et Marie Curie, F-75005 Paris, France; Institut National de la Recherche Agronomique UMR85 Physiologie de la Reproduction et des Comportements (M.M., I.F., M.K.) and CNRS UMR7247 (M.M., I.F., M.K.), F-37380 Nouzilly, France; and Université François Rabelais (M.M., I.F., M.K.), F-37000 Tours, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Picot
authors.forename: Lydie
authors.initials: L
authors.lastname: Naulé
authors.forename: Clarisse
authors.initials: C
authors.lastname: Marie-Luce
authors.forename: Mariangela
authors.initials: M
authors.lastname: Martini
authors.forename: Kalina
authors.initials: K
authors.lastname: Raskin
authors.forename: Valérie
authors.initials: V
authors.lastname: Grange-Messent
authors.forename: Isabelle
authors.initials: I
authors.lastname: Franceschini
authors.forename: Matthieu
authors.initials: M
authors.lastname: Keller
authors.forename: Sakina
authors.initials: S
authors.lastname: Mhaouty-Kodja
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects; D059648:Kisspeptins / Q000378:metabolism; D008297:Male; D051379:Mice; D009415:Nerve Net / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage*; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D012903:Smell / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D059648:Kisspeptins; D010636:Phenols; D011944:Receptors, Androgen; C006780:bisphenol A; D000098826:Bisphenol A Compounds