Gestational exposure to bisphenol A and cross-fostering affect behaviors in juvenile mice

Abstract

Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern has been raised about its potential negative effects on human health. BPA is an estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined effects of gestational exposure to BPA on several behaviors in C57BL/6J mice. Because BPA affects maternal care, which, may have long-lasting effects on offspring behavior, we tested mice raised by either biological or fostered dams. Both diet and dam affected behavior in juvenile mice in a social novelty task and the elevated plus maze (EPM). In a social novelty task, the amount of time spent interacting with an adult male was affected by sex and gestational diet, but only in juveniles raised by a foster dam. Control females spent less time sniffing a novel adult than did control males or females exposed to BPA during gestation. In the EPM, juveniles reared by foster dams and exposed to BPA during gestation spent less time in the distal half of the open arm as compared with juveniles gestated on a control diet. Adult offspring raised by their biological dams showed the same response pattern; gestational BPA increased anxiety as compared with control diet. Our results show that prenatal BPA exposure affects social behavior and anxiety in the EPM. Moreover, some facet(s) of the infant-maternal interaction may modify these effects.

Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A

“…In our experiments, maternal diet exposure to BPA was 50 mg BPA/kg feed weight, which is consistent with prior studies that have demonstrated that such a dose can induce epigenetic (21) and behavioral changes (22) in laboratory rodents. It was designed to be well below the diet-administered maximum nontoxic dose for rodents (200 mg/kg body weight per day), within the presumptive no observed effect level for mice (23), and likely to provide circulating serum concentrations close to those observed for humans (24).…”

Bisphenol S (BPS) alters maternal behavior and brain in mice exposed during pregnancy/lactation and their daughters

“…It is important to note that effects on the mother may affect her offsprings' behavioral and neural development (97). One major challenge is to distinguish the direct effects of EDC exposures on the pups from indirect effects observed in pups due to altered maternal behaviors (28,29,98). In a small number of studies, cross-fostering has been used to isolate the "direct" effects of EDC exposures on the mother's behavior from "indirect" effects on offspring (29, 98, 99).…”

“…Cross-fostering experiments will be necessary to delineate whether the effects of exposures on the F1 generation are direct or indirect. However, care must be taken in study design as maternal behavior can be affected in both a positive and negative direction by crossfostered pups (29,(100)(101)(102).…”

Maternal exposure to bisphenol A and genistein has minimal effect onAvy/aoffspring coat color but favors birth of agouti over nonagouti mice

“…This observation is important, as BPA is a chemical ubiquitous in the environment and may disrupt a range of processes controlled through steroid receptors, particularly ESR1 (24)(25)(26). In view of the importance of the effects of diet on the expression of the A vy allele and considerable media and scientific attention paid to the papers describing the phenomenon (22,23), we have examined the coat color pattern distribution of A vy /a offspring born to a/a dams exposed to three doses of BPA, ranging from relatively high (50 mg/kg fw) to low (50 μg/kg fw), but all within the "no observable adverse effect level" (27). We have also tested whether the upper 50-mg dose of BPA in combination with G, G alone, and ethinyl estradiol (EE), which provides a positive estrogen control, had any effects on coat color relative to controls where the dam had been fed a phytoestrogen-free refined diet.…”