Article

Bisphenol A, an endocrine-disrupting chemical, and brain development

Department of Pathology & Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Neuropathology (Impact Factor: 1.8). 01/2012; 32(4):447-57. DOI: 10.1111/j.1440-1789.2011.01287.x
Source: PubMed

ABSTRACT Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in various industries and the field of dentistry. The consequent increase in BPA exposure among humans has led us to some concerns regarding the potential deleterious effects on reproduction and brain development. The emphasis of this review is on the effects of prenatal and lactational exposure to low doses of BPA on brain development in mice. We demonstrated that prenatal exposure to BPA affected fetal murine neocortical development by accelerating neuronal differentiation/migration during the early embryonic stage, which was associated with up- and down-regulation of the genes critical for brain development, including the basic helix-loop-helix transcription factors. In the adult mice brains, both abnormal neocortical architecture and abnormal corticothalamic projections persisted in the group exposed to the BPA. Functionally, BPA exposure disturbed murine behavior, accompanied with a disrupted neurotransmitter system, including monoamines, in the postnatal development period and in adult mice. We also demonstrated that epigenetic alterations in promoter-associated CpG islands might underlie some of the effects on brain development after exposure to BPA.

Download full-text

Full-text

Available from: Kyoko Itoh, Nov 20, 2014
2 Followers
 · 
150 Views
  • Source
    • "In addition to these " high dose " effects on survival and growth, other studies have shown a variety of effects induced by much lower doses of BPA, i.e. doses below the established NOAEL of 50 ␮g/kg/day, which reproduce better the actual human exposure. The adverse effects induced by a " low dose " of BPA include neuronal and behavioral alterations: documented effects of prenatal exposure to BPA are abnormal development of the neocortex in terms of differentiation and neuronal migration [19] [38], aberrant positions and connections between thalamus and cortex [39], inhibition of the proliferation of neural progenitor cells [21], loss of sexual dimorphism in terms of brain structure and behavior [24], increased anxiety and cognitive deficits [45] [54]. Part of these results are justified by the strong affinity of BPA to the dopamine receptor, the estrogen-like receptor-␤ type [8] and the estrogen-like receptor-␥ type present in hippocampal neurons [51]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over 50% of the causes of fetal malformations in humans are still unknown. Recent evidence suggests the relationship between environmental exposure to endocrine disruptors and fetal malformations. Our study aims to establish the role of Bisphenol A (BPA), if any, in altering human reproduction. We enrolled 151 pregnant women who were divided into two groups: case group (CS, n=101), women with established diagnosis of developmental defect, and control group (CL, n=50), pregnant women with normally developed fetus. Total, free and conjugated BPA were measured in their blood using GC-MS with isotopic dilution. The results show a correlation between environmental exposure to BPA and the genesis of fetal malformations. Conjugated BPA, which was higher in the CL, casts light on the hypothesis that a reduced ability to metabolize the chemical in the mother can concur to the occurrence of malformation. In a more detailed manner, in case of chromosomal malformations, the average value of free BPA appears to be nearly three times greater than that of the controls. Similarly, in case of central and peripheral nervous system non-chromosomal malformations, the value of free BPA is nearly two times greater than that of the controls. Copyright © 2015 Elsevier B.V. All rights reserved.
    Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 03/2015; 774. DOI:10.1016/j.mrfmmm.2015.02.007
  • Source
    • "BPA can accelerate neuronal differentiation/migration during the early embryonic stage (Itoh et al., 2012). Of these studies, the time of BPA exposure is concentrated in gestation and/or lactation, while only a few reports investigated the effects of fetal growth and development stage exposure to BPA (Itoh et al., 2012; Komada et al., 2012). A number of reports have shown non-reproductive behavior modifications, including learning and memory, after exposure to BPA (Cox et al., 2010; Jašareví c et al., 2012; Meng et al., 2011; Xu et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to adversely impact the central nervous system, especially with respect to learning and memory. However, the precise effect and specific mechanisms have not been fully elucidated. In the present study, pregnant Sprague-Dawley rats were orally administered with BPA at 0.05, 0.5, 5 or 50mg/kg·body weight (BW) per day from embryonic day 9 (E 9) to E 20. We examined the effects of maternal BPA exposure on memory and synaptic structure in the hippocampus of male offspring at postnatal day (PND) 21. Maternal BPA exposure significantly affected locomotor activity, exploratory habits, and emotional behavior in open field test, and increased reference and especially working memory errors in the radial arm maze during the postnatal developing stage. Maternal BPA exposure had an adverse effect on synaptic structure, including a widened synaptic cleft, a thinned postsynaptic density (PSD), unclear synaptic surface and disappeared synaptic vesicles. Furthermore, maternal BPA exposure decreased the mRNA and protein expressions of synaptophysin, PSD-95, spinophilin, GluR1 and NMDAR1 in the hippocampus of male offspring on PND 21. These results showed that fetal growth and development was more sensitive to BPA exposure. The decreased learning and memory induced by maternal exposure to BPA in this study may be involved in synaptic plasticity alteration.
    Toxicology 05/2014; 322. DOI:10.1016/j.tox.2014.05.001 · 3.75 Impact Factor
  • Source
    • "BPA can be detected in human blood, plasma, urine, saliva, amniotic fluid, placental tissue, follicular fluid, breast milk, and adipose tissue (Vandenberg et al., 2010). Many studies have shown that BPA poses potential risks to reproduction and development due to its estrogenic effects (Susiarjo et al., 2007; Itoh et al., 2012). Aoki and Takada showed that BPA might affect ovarian and testicular development as well as germ cell differentiation, and appeared to induce genes responsible for ovary development (Aoki and Takada, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bisphenol A (BPA) poses potential risks to reproduction and development. However, the mechanism of BPA's effects on early embryonic development is still unknown. Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro models for testing the toxic effects of environmental chemicals in early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were exposed to BPA up to 6 days and their differentiation capacity was evaluated. In mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of endodermal markers (Gata4, Sox17) and mesodermal markers (Sma, Desmin), and reduced the mRNA levels of ectodermal markers (Nestin, Fgf5) in mEB. Furthermore, microRNA(miR)-134, an expression inhibitor of pluripotency markers including Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These results firstly indicate that BPA may disturb pluripotency in mESC and differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB while miR-134 may play a key role underlying this effect.
    Toxicology in Vitro 09/2013; 27(8). DOI:10.1016/j.tiv.2013.09.018 · 3.21 Impact Factor
Show more