This Article Full Text Full Text (PDF) All Versions of this Article: 147/8/3681    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rubin, B. S. Articles by Soto, A. M. Search for Related Content PubMed PubMed Citation Articles by Rubin, B. S. Articles by Soto, A. M.

Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A

Tufts University, School of Medicine, Boston, Massachusetts 02111

Address all correspondence and requests for reprints to: Beverly S. Rubin, Department of Anatomy and Cellular Biology, 136 Harrison Avenue, Boston, Massachusetts 02111. E-mail: beverly.rubin{at}tufts.edu.

Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable of altering important events during critical periods of brain development.

This article has been cited by other articles:

				G. Rasier, A.-S. Parent, A. Gerard, R. Denooz, M.-C. Lebrethon, C. Charlier, and J.-P. Bourguignon Mechanisms of Interaction of Endocrine-Disrupting Chemicals with Glutamate-Evoked Secretion of Gonadotropin-Releasing Hormone Toxicol. Sci., March 1, 2008; 102(1): 33 - 41. [Abstract] [Full Text] [PDF]

				J. S. Brown Jr Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia Schizophr Bull, January 31, 2008; (2008) sbm147v1. [Abstract] [Full Text] [PDF]

				L. Monje, J. Varayoud, E. H Luque, and J. G Ramos Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor {alpha} transcripts with alternative 5'-untranslated regions in the female rat preoptic area J. Endocrinol., July 1, 2007; 194(1): 201 - 212. [Abstract] [Full Text] [PDF]

				L. N. Vandenberg, M. V. Maffini, P. R. Wadia, C. Sonnenschein, B. S. Rubin, and A. M. Soto Exposure to Environmentally Relevant Doses of the Xenoestrogen Bisphenol-A Alters Development of the Fetal Mouse Mammary Gland Endocrinology, January 1, 2007; 148(1): 116 - 127. [Abstract] [Full Text] [PDF]

				F. S. vom Saal Bisphenol a eliminates brain and behavior sex dimorphisms in mice: how low can you go? Endocrinology, August 1, 2006; 147(8): 3679 - 3680. [Full Text] [PDF]