Bisphenol A: An endocrine and metabolic disruptor

Inserm U1065/C3M, service d'endocrinologie, diabétologie et reproduction, hôpital de l'Archet 2, CHU de NICE, 151, route Saint-Antoine-de-Ginestière, 06202 Nice cedex 3, France. Electronic address: .
Annales d Endocrinologie (Impact Factor: 0.87). 06/2013; 74(3). DOI: 10.1016/j.ando.2013.04.002
Source: PubMed


Bisphenol A (BPA), initially designed, like diethylstilbestrol, as a synthetic estrogen, has been rapidly and widely used for its cross-linking properties in the manufacture of polycarbonate plastics and epoxy resins. Because of incomplete polymerization and degradation of the polymers by exposure to higher than usual temperatures, BPA leaches out from food and beverage containers, as well as from dental sealants. In humans, free active unconjugated BPA is metabolized by rapid glucurono- or sulfo-conjugation and eliminated via renal clearance. However, exposure to environmental nanomolar concentrations of BPA is ubiquitous and continuous via different routes: oral, air, skin. In rodents, fetal and perinatal exposure to such environmentally relevant doses of BPA has been shown to affect the brain, liver, gut, adipose tissue, endocrine pancreas, mammary gland and reproductive tract and function. Similar concentrations are also able in vitro to impact human malignant breast, prostate, male germ or adipocyte cell lines (with a promoting effect and by interfering with chemotherapy drugs), or to stimulate pancreatic β cell insulin secretion. High levels of BPA have recently been correlated with obesity, diabetes, cardiovascular diseases, polycystic ovarian disease or low sperm count. However, before the real impact of BPA on human health can be clearly assessed, prospective longitudinal epidemiological studies are needed as well as characterization of selective biomarkers to verify long-term exposure and selective imprinting.

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    • "Acting both at genetic and at epigenetic levels, these influences seem to modify the physiological programming of energy homeostasis with an imprinting mechanism that becomes evident much later in life (Dyer and Rosenfeld 2011). Even though not all the authors agree (Sharpe and Drake 2010), there is now increasing concern on the involvement of early-life exposure to low BPA in the onset of human obesity and related metabolic complications (Fenichel et al. 2013; Le Corre et al. 2013). "
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    ABSTRACT: Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose–response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health.
    Dose-Response 06/2015; 13(2). DOI:10.1177/1559325815590394 · 1.22 Impact Factor
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    • "Nine out of ten Americans tested positive with BPA in random urine samples (Lassen et al. 2014). In a study measuring BPA in breast adipose tissue, more than half of the examined samples had detectable BPA levels (Fenichel et al. 2013). "
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    ABSTRACT: Humans are exposed to low dose Bisphenol A (BPA) through plastic consumer products and dental sealants with BPA. While a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies. The objective of this study is to investigate the effect and the mechanism of low dose BPA in mammary gland cells. We evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA's effects. Low-dose BPA significantly promoted DNA damage, upregulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells. Low-dose BPA exerted c-Myc-dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.
    Environmental Health Perspectives 05/2015; DOI:10.1289/ehp.1409199 · 7.98 Impact Factor
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    • "Due to exponential use of synthetic chemicals combined with delayed actions taken for their regulation, advances in exposure sciences combined with improved analytical methodologies evidenced the widespread human and animal exposure to such chemicals (Meeker, 2012). Apart from these, some compounds, such as bisphenol A (BPA) or triclosan (TCS), are capable of disrupting endocrine functions through mimicking or blocking endogenous hormones (Fenichel et al., 2013; Koeppe et al., 2013; Schug et al., 2011). Alterations in thyroid and steroid hormone function and activation of peroxisome proliferator-activated receptors might occur due to exposure to such endocrine disrupting chemicals (EDCs) influencing the adipocyte differentiation a'nd energy storage (Tang-Péronard et al., 2011; Thayer et al., 2012). "
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    ABSTRACT: Bisphenol A (BPA) and triclosan (TCS) were determined in urine of Belgian overweight and obese (n = 151) and lean (n = 43) individuals. After the first urine collection (0 M), obese patients started a diet program or have undergone bariatric surgery. Hereafter, three additional urine samples from obese patients were collected after 3 (3M), 6 (6M) and 12 (12 M) months. Both compounds were detected in N99% of the samples. BPA had median concentrations of 1.7 and 1.2 ng/mL in obese and lean groups, respectively, while TCS had median concentrations of 1.5 and 0.9 ng/mL in the obese and lean groups, respectively. The obese group had higher urinary concentrations (ng/mL) of BPA (p b 0.5), while no significant differences were found for TCS between the obese and lean groups. No time trends between the different collection moments were observed. The BPA concentrations in the obese group were negatively associated with age, while no gender difference or relationship with body mass index was observed. For TCS, no relationships with gender, BMI, or age were found. The temporal variability of BPA and TCS was assessed with calculation of the intra class correlation coefficient, Spearman rank correlation coefficients, and surrogate category analysis. We observed evidence that single spot urine samples might be predictive of exposure over a longer period of time. Dietary intakes of BPA and TCS did not differ significantly among the time points considered after obese individuals started losing weight (6 and 12 months). Multiple linear regression analyses after adjusting for age and weight loss revealed negative associations between urinary TCS and serumFT4 in the 0M and 3M female obese individuals and positive associations between urinary BPA and serum TSH in the lean group.
    Environment international 01/2015; 76(March 2015):98-105. DOI:10.1016/j.envint.2014.12.003 · 5.56 Impact Factor
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