Abstract

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist- antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a “pure” estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies.

Highlights

  • Bisphenol A (BPA) is an endocrine disrupting compound (EDC) present in a wide assortment of plastic and cardboard items, dental sealants, and other products [1,2,3]

  • As spatial learning may not be under strong sexual selection in the California mice [44], we predicted that developmental BPA exposure would not lead to a sex-dependent disruption of spatial learning in this species

  • Developmental exposure to BPA and ethinyl estradiol (EE) failed to influence the behavior of males in the elevated plus maze (EPM), again providing a contrast with the earlier deer mouse study, in which males showed higher anxietylike behavior following developmental BPA exposure [35]

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Summary

Introduction

Bisphenol A (BPA) is an endocrine disrupting compound (EDC) present in a wide assortment of plastic and cardboard items, dental sealants, and other products [1,2,3]. BPA acts predominantly through estrogen receptor-a and –b (ESR1 and 2), but effects operating through other steroid receptors and pathways have been inferred [4]. Fetuses and neonates lack many of the enzymes needed to metabolize BPA and may, experience greater concentrations of active BPA than the dam [10,11,12]. This development period is characterized by programming of the brain by steroid hormones [14,15,16].

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