Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice Lydie Naule ´ 1,2,3 , Marie Picot 1,2,3 , Mariangela Martini 4,5,6 , Caroline Parmentier 1,2,3 , He ´le `ne Hardin-Pouzet 1,2,3 , Matthieu Keller 4,5,6 , Isabelle Franceschini 4,5,6 and Sakina Mhaouty-Kodja 1,2,3 1 Sorbonne Universite ´ s, UPMC University Paris 06, UMR 7224, 2 Institut National de la Sante ´ et de la Recherche Me ´ dicale (INSERM) UMR_S 952 and 3 Centre National de la Recherche Scientifique (CNRS) UMR 7224, Physiopathologie des Maladies du Syste ` me Nerveux Central (PMSNC), Universite ´ Pierre et Marie Curie, 9 Quai St Bernard Ba ˆ t B 2e ` me E ´ tage, F75005 Paris, France 4 Institut National de la Recherche Agronomique (INRA) UMR85, Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France 5 CNRS UMR 7247, F-37380 Nouzilly, France 6 Universite ´ Franc ¸ois Rabelais, F-37000 Tours, France Correspondence should be addressed to S Mhaouty-Kodja Email sakina.mhaouty-kodja@ snv.jussieu.fr 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 (E 2 ) 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 E 2 , through estrogen receptor a, during the postnatal/prepubertal period. Key Words " bisphenol A " female mice " nervous system " reproduction " behaviors " kisspeptin Journal of Endocrinology (2014) 220, 375–388 Introduction Bisphenol A (BPA) is one of the most abundant endocrine disrupters. It is used in epoxy resins and a wide variety of polycarbonate containers for the storage of foods and beverages. Environmental and health concerns about the extensive use of polycarbonate plastic have been raised, in particular, concerning BPA leaching from plastic. Journal of Endocrinology Research L NAULE ´ and others Gestational and lactational BPA in female mice 220 :3 375–388 http://joe.endocrinology-journals.org Ñ 2014 Society for Endocrinology DOI: 10.1530/JOE-13-0607 Printed in Great Britain Published by Bioscientifica Ltd.