Neurosciences
Program

Bernstein, J.E., Kircher, D.M., and Brady, A.M.  (2011, June).  Developmental exposure to low doses of bisphenol-A:  Sex-dependent effects in adult offspring. 

Poster presented at the Organization for the Study of Sex Differences Annual Meeting, Oklahoma City, OK.

Abstract 

The endocrine-disrupting chemical bisphenol-A (BPA) is a common component of food containers and baby bottles.  BPA is known to leach out of these containers into food and drink, and evidence for long-term deleterious effects of BPA exposure, particularly during development, is beginning to emerge.  In animals, developmental exposure to low doses of BPA can lead to enduring changes in physiology and behavior in adulthood.  Here, we examined the effects of indirect, perinatal exposure to low doses of BPA (20 or 50 µg/kg/day) on dopamine-driven locomotion and on spatial cognition in adult male and female Sprague-Dawley rats.  Both doses of BPA are at or below the EPA’s estimated safe oral exposure level of 50 µg/kg/day.  BPA was administered orally to pregnant and lactating dams from embryonic day 14 through postnatal day (PD) 20.  Male and female offspring were weaned at PD21, and were assessed on a battery of behavioral tests beginning on or around PD60.  Perinatal exposure to BPA increased spontaneous locomotor activity in both males and female adult offspring.  However, the most effective dose of BPA differed in males and females; exposure to the lower dose (BPA-20) increased locomotor activity most strongly in adult females, while the higher dose (BPA-50) was more effective in males.  In control animals, acute administration of the dopamine-releasing psychostimulant drug amphetamine (0, 1 and 2 mg/kg, in counterbalanced order) increased locomotion more robustly in females than in males, but dose-dependent effects of amphetamine were observed in males only.  Developmental exposure to BPA had qualitatively different effects on amphetamine-induced locomotion in adult male and female offspring.  In males, the dose-dependency of amphetamine’s effects was abolished by exposure to the higher dose of BPA (BPA-50); in females, exposure to the lower dose of BPA (BPA-20) enhanced amphetamine’s stimulatory effect on locomotion, and elicited a dose-dependency that was not present in control females.  The effects of BPA exposure on spatial learning and memory, assessed in the Morris water maze, were also sex-dependent.  Spatial learning and recall in adult males was impaired by exposure to BPA-50, while spatial cognition in females appeared to be enhanced by exposure to BPA-20.  Control females performed worse than control males in the water maze.  Two main themes emerge from these results.  First, female offspring were more sensitive to the lower level of perinatal BPA exposure (BPA-20), while males were generally more sensitive to the higher dose (BPA-50).  Second, females developmentally exposed to BPA displayed behaviors that were typical of control males, particularly for spatial cognition, suggesting a masculinizing effect of perinatal BPA.  Together, these results provide further evidence that even indirect exposure to low levels of the endocrine disruptor BPA can have lasting effects on dopamine-dependent behaviors and cognition, and that such effects are strongly sex-dependent.