title: Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice.
abstract: Bisphenol A (BPA) is a widespread estrogenic compound. We investigated the effects of maternal exposure to BPA at reference doses on sexual behavior and neuroendocrine functions of female offspring in C57BL/6J mice. The dams were orally exposed to vehicle alone or vehicle-containing BPA at doses equivalent to the no observed adverse effect level (5 mg/kg body weight per day) and tolerable daily intake (TDI, 0.05 mg/kg body weight per day) level from gestational day 15 until weaning. Developmental exposure to BPA increased the lordosis quotient in naive females exposed to BPA at the TDI dose only. BPA exposure had no effect on olfactory preference, ability to express masculine behaviors or number of calbindin-positive cells, a sexually dimorphic population of the preoptic area. BPA at both doses selectively increased kisspeptin cell number in the preoptic periventricular nucleus of the rostral periventricular area of the third ventricle in adult females. It did not affect the number of GNRH-positive cells or percentage of kisspeptin appositions on GNRH neurons in the preoptic area. These changes were associated with higher levels of estradiol (E2) at the TDI dose while levels of LH, estrus cyclicity, ovarian and uterine weights, and fertility remained unaffected. Delay in the time of vaginal opening was observed during the postnatal period at TDI dose, without any alteration in body growth. This shows that developmental exposure to BPA at reference doses did not masculinize and defeminize the neural circuitry underlying sexual behavior in female mice. The TDI dose specifically exacerbated responses normally induced by ovarian E2, through estrogen receptor α, during the postnatal/prepubertal period.
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UMR 7224Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 952 and Centre National de la Recherche Scientifique (CNRS) UMR 7224, Physiopathologie des Maladies du Système Nerveux Central (PMSNC), Université Pierre et Marie Curie, <br/>9 Quai St Bernard Bât B 2ème Étage, F75005 Paris, France Institut National de la Recherche Agronomique (INRA) UMR85, Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR 7247, F-37380 Nouzilly, France Université François Rabelais, F-37000 Tours, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Naulé
authors.forename: Marie
authors.initials: M
authors.lastname: Picot
authors.forename: Mariangela
authors.initials: M
authors.lastname: Martini
authors.forename: Caroline
authors.initials: C
authors.lastname: Parmentier
authors.forename: Hélène
authors.initials: H
authors.lastname: Hardin-Pouzet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Keller
authors.forename: Isabelle
authors.initials: I
authors.lastname: Franceschini
authors.forename: Sakina
authors.initials: S
authors.lastname: Mhaouty-Kodja
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism / Q000523:psychology*; D011301:Preoptic Area / Q000187:drug effects; D012726:Sexual Behavior, Animal / Q000187:drug effects; D014599:Uterus / Q000254:growth & development / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: behaviors; bisphenol A; female mice; kisspeptin; nervous system; reproduction