Multi- and Transgenerational Consequences of Bisphenol A on Sexually Dimorphic Cell Populations in Mouse Brain.

Bisphenol A (BPA) is an endocrine-disrupting compound used to manufacture plastics; it is present in linings of food cans, bottles, thermal receipts, and many other everyday items and is detectable in human urine and blood. Exposure to BPA during development can disrupt sexual differentiation of some brain regions. Moreover, BPA can have transgenerational effects on gene expression and behaviors. Here, we used a diet and breeding regimen that produces transgenerational effects on behaviors. C57BL/6J mice consumed control or BPA-containing diets during pregnancy. We examined vasopressin (AVP) and estrogen receptor α (ERα) immunoreactivity (ir) in sexually dimorphic brain regions from first-generation (F1) offspring and transgenerational effects of BPA in third-generation offspring. In all but one brain region examined, the expected sex differences were noted in both generations of control mice. In F1 mice, a diet by sex interaction was present for AVP-ir in the lateral septum and posterodorsal medial amygdala. In both regions, BPA exposure reduced immunoreactivity in male brains. An interaction between diet and sex for ERα-ir in the ventromedial hypothalamus was caused by reduced immunoreactivity in BPA-exposed females. Of interest, BPA had transgenerational effects on ERα-ir in the anteroventral periventricular nucleus and bed nucleus of the stria terminalis. Our data show that BPA produces immunoreactive differences in ERα-ir generations after exposure to BPA. We speculate that actions of BPA in utero on ERα-ir in brain have long-term consequences for reproduction and social behavior.