A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development.

Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats. BPA was orally administered at a daily dose of 5 μg/kg body weight to F0 pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to F1 offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as "non-maternal" behaviors in F0 and F1 dams from parturition until LD 8. The flavor preferences of F1 and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21-34 and PND 86-99. BPA exposure: 1) decreased maternal behavior in F1 dams, 2) caused developmental defects in both F1 and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in F1, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change. Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure.