Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice

Kimura, Eiki; Matsuyoshi, Chieri; Miyazaki, Wataru; Benner, Seico; Hosokawa, Mayuko; Yokoyama, Kazuhito; Kakeyama, Masaki; Tohyama, Chiharu

doi:10.1007/s00204-015-1485-x

Cited by 58 publications

(41 citation statements)

References 64 publications

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“…A single dose of BPA administered to neonatal mice was observed to affect cognitive function and alter adult spontaneous behavior, with the effect being seen in mid and high dosed mice [81]. In utero exposure to BPA in mice was shown to reduce dendritic spine densities in the hippocampal CA1 region, regardless of its dose [82]. BPA was demonstrated to impair neural ectoderm specification and neural progenitor cells in mouse embryonic stem cells [83].…”

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Preciados

Yoo

Roy

2016

IJMS

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During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD—APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF—underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely ...

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Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Preciados

Yoo

Roy

2016

IJMS

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“…Bisphenol A (BPA; 2,2-bis [4-hydroxyphenyl]propane) is an industrial chemical widely used in the manufacture of polycarbonate plastics and epoxy resin liners for aluminum cans [1][2][3][4][5][6][7]. BPA is an endocrine-disrupting chemical (EDC) that has been demonstrated to affect reproductive organ development [7][8][9], brain development [10][11][12][13][14][15], metabolic diseases [16], and postnatal behavior [17][18][19]. These adverse effects are thought to be due to disturbed signaling mechanisms involving estrogen, androgen, and thyroid hormone.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of Bisphenol A and Its Adverse Effects on the Next Generation

Iwano¹,

Inoue²,

Nishikawa³

et al. 2018

Endocrine Disruptors

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Although we are exposed to many chemical substances in routine daily life, the body has metabolic systems capable of detoxifying and eliminating these chemicals. Bisphenol A (BPA) is an endocrine disrupter of great concern because of its estrogenic activity, but studies have indicated no severe adverse effects in adult rodents exposed to BPA due to metabolic detoxification. BPA is metabolized by glucuronidation mediated by phase II enzymes such as UDP-glucuronosyltransferase. Numerous recent studies in rodents have indicated that maternal BPA exposure causes adverse effects in offspring. It was also shown that bisphenol analogs are efficiently absorbed via the oral route and distributed to the reproductive tract in pregnant rats, with its residue capable of crossing the placental barrier in the late stage of gestation. Both animal and human studies have demonstrated that BPA and the BPA metabolite BPA-GA are detectable in fetal and amniotic fluid, suggesting the presence of a placental transfer mechanism. In this review, we discuss the pharmacokinetics of BPA, particularly its (1) metabolism and disposition in the intestine, (2) metabolism and disposition in the liver, and (3) transfer from maternal tissues to the fetus.

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“…Gestational BPA exposure (GD8.5 – GD18.5; 40 or 400 μg/kg) reduced spine density in CA1 pyramidal cells at 14 months in mice. The apical dendritic tree was also reduced (Kimura et al ., ). Treatment of adult ovariectomized rats with a dose of 40, 120, or 400 μg/kg of BPA dose dependently reduced the number of spines in the CA1 hippocampal region and also inhibited the spine increase caused by estradiol (MacLusky et al ., ).…”

Section: Mechanisms Of Action Of Edcs In the Brain: Insights From Rodmentioning

confidence: 97%

Exposure to endocrine disrupting chemicals and neurodevelopmental alterations

2016

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SUMMARYThe developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling.

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Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice

Cited by 58 publications

References 64 publications

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Biotransformation of Bisphenol A and Its Adverse Effects on the Next Generation

Exposure to endocrine disrupting chemicals and neurodevelopmental alterations

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