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

Humans are routinely exposed to bisphenol A (BPA), an es- trogenic chemical present in food and beverage containers, dental composites, and many products in the home and work- place. 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 d8o fgestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hy- droxylase (TH) neurons in the rostral periventricular preop- tic 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 dimin- ished 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 sex- ual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Datafromthesestudiesrevealedsignificantsexdifferencesin the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capableofalteringimportanteventsduringcriticalperiodsof brain development. (Endocrinology 147: 3681-3691, 2006)