Effects of Prenatal Exposure to a Low-Dose of Bisphenol A on Sex Differences in Emotional Behavior and Central Alpha2-Adrenergic Receptor Binding.

Davide Ponzi,Paola Palanza,Laura Gioiosa,Stefano Parmigiani

doi:10.3390/ijms21093269

Davide Ponzi, Paola Palanza + Show 2 more

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https://doi.org/10.3390/ijms21093269

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Abstract

Prenatal exposure to bisphenol A (BPA) influences the development of sex differences neurologically and behaviorally across many species of vertebrates. These effects are a consequence of BPA’s estrogenic activity and its ability to act as an endocrine disrupter even, at very low doses. When exposure to BPA occurs during critical periods of development, it can interfere with the normal activity of sex steroids, impacting the fate of neurons, neural connectivity and the development of brain regions sensitive to steroid activity. Among the most sensitive behavioral targets of BPA action are behaviors that are characterized by a sexual dimorphism, especially emotion and anxiety related behaviors, such as the amount of time spent investigating a novel environment, locomotive activity and arousal. Moreover, in some species of rodents, BPA exposure affected males’ sexual behaviors. Interestingly, these behaviors are at least in part modulated by the catecholaminergic system, which has been reported to be a target of BPA action. In the present study we investigated the influence of prenatal exposure of mice to a very low single dose of BPA on emotional and sexual behaviors and on the density and binding characteristics of alpha2 adrenergic receptors. Alpha2 adrenergic receptors are widespread in the central nervous system and they can act as autoreceptors, inhibiting the release of noradrenaline and other neurotransmitters from presynaptic terminals. BPA exposure disrupted sex differences in behavioral responses to a novel environment, but did not affect male mice sexual behavior. Importantly, BPA exposure caused a change in the binding affinity of alpha2 adrenergic receptors in the locus coeruleus and medial preoptic area (mPOA) and it eliminated the sexual dimorphism in the density of the receptors in the mPOA.

Highlights

Bisphenol A (BPA) is an environmentally ubiquitous monomer used in the synthesis of polycarbonate plastics and epoxy resins that are employed in the manufacturing of food and beverage containers and dental sealants [1]
Based on our previously reported sex-dependent effects of prenatal exposure to BPA on behavioral responses mediated by the catecholaminergic system of the house mouse [44], in the present study we investigated whether the exposure to the same low dose of BPA (10 μg/Kg BW) had long term, sex dependent disruptive effects on the noradrenergic system
We could not find sex differences in terms of receptor density, our preliminary analysis suggests that in the preoptic area of the control group, males might have lower density compared to females

Summary

Introduction

Bisphenol A (BPA) is an environmentally ubiquitous monomer used in the synthesis of polycarbonate plastics and epoxy resins that are employed in the manufacturing of food and beverage containers and dental sealants [1]. Owing to its ability to bind intracellular and membrane-associated estrogen receptors, BPA acts to endogenous estrogen leading to the activation of genomic and nongenomic mechanisms [6] that, during period of early development and plasticity, have long term effects on several neuroendocrine systems [7,8] and behaviors [9]. In this regard, abundant experimental data show that BPA can interfere with the development of the central nervous system at doses below its US reference dose of 50 ug/kg/day and within the estimated daily intake for adults and children [10]. Through its aromatization to estradiol, in rodents testosterone causes masculinization and defeminization of males’ brain structures and of behaviors under their control [12]

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