Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May 5;21(9):3269.
doi: 10.3390/ijms21093269.

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  1 , Laura Gioiosa  1 , Stefano Parmigiani  2 , Paola Palanza  1
Affiliations

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 et al. Int J Mol Sci. .

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.

Keywords: alpha2 adrenergic receptors; bipshenol A; catecholamines; estrogen; ethology; sex differences.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of prenatal BPA exposure on behavioral responses of male and female mice in the free exploratory open field. (OIL: 14 males and 14 females; BPA: 14 males and 14 females). Dark columns = males. * p < 0.05 males vs. females BPA. Data are presented as mean ±SE.
Figure 2
Figure 2
Effects of prenatal BPA exposure on behaviors in the elevated plus maze. (OIL: 14 males and 14 females; BPA: 14 males and 14 females); Dark columns = males. * p < 0.05, OIL males vs. OIL females; ** p < 0.01, OIL males vs. OIL females; + p = 0.06, OIL females vs. BPA females; a p < 0.05, OIL females vs. BPA females; aa p < 0.01, OIL females vs. BPA males; # p < 0.05 BPA group vs. OIL group. Data are presented as mean ± SE.
Figure 3
Figure 3
Effects of prenatal exposure to BPA on alpha2 adrenergic receptor affinity in the locus coeruleus and preoptic area. Binding curves for preoptic area of control (a) and BPA (b) groups. (c) Affinity (Kd) in the locus coeruleus; (d) affinity in the preoptic area. (OIL: eight males and eight females; BPA: eight males and seven females). Dark columns = males. * p < 0.05 OIL females vs. BPA females; # p < 0.05 BPA vs. OIL. Data are presented as mean ±SE. POA = preoptic area.
Figure 4
Figure 4
Autoradiograms showing the distributions of alpha2-adrenergic receptors in the preoptic area (POA, left) and locus coeruleus (LC, right). Red = higher density of alph2-adrenergic receptors.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Vandenberg L.N., Hauser R., Marcus M., Olea N., Welshons W.V. Human exposure to bisphenol A (BPA) Reprod. Toxicol. 2007;24:139–177. doi: 10.1016/j.reprotox.2007.07.010. - DOI - PubMed
    1. Schönfelder G., Wittfoht W., Hopp H., Talsness C.E., Paul M., Chahoud I. Parent bisphenol a accumulation in the human maternal-fetal-placental unit. Environ. Health Perspect. 2002;110 doi: 10.1289/ehp.110-1241091. - DOI - PMC - PubMed
    1. Ikezuki Y., Tsutsumi O., Takai Y., Kamei Y., Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum. Reprod. 2002;17:2839–2841. doi: 10.1093/humrep/17.11.2839. - DOI - PubMed
    1. Sun Y., Irie M., Kishikawa N., Wada M., Kuroda N., Nakashima K. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed. Chromatogr. 2004;18:501–507. doi: 10.1002/bmc.345. - DOI - PubMed
    1. vom Saal F.S., Welshons W.V. Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure. Mol. Cell. Endocrinol. 2014;398:101–113. doi: 10.1016/j.mce.2014.09.028. - DOI - PMC - PubMed

MeSH terms