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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    • "In animals, fetal or perinatal exposure to BPA has been shown to affect hormone levels (Rubin et al., 2001; Ramos et al., 2003; Alonso- Magdalena et al., 2010; Fenichel et al., 2013), reproductive tract morphology and function (vom Saal et al., 1998; Newbold et al., 2009), puberty (Howdeshell et al., 1999), male sexual behavior (Jones et al., 2011) and adult expression of sexually selected traits (Jasarevic et al., 2011). In humans, exposure to environmental or occupational levels of BPA has been associated with birth outcomes (Wolff et al., 2008; Philippat et al., 2012; Tang et al., 2013), puberty in boys (Ferguson et al., 2014), semen quality (Meeker et al., 2010) and declining male sexual function (Li et al., 2010). "
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    ABSTRACT: STUDY QUESTION Are maternal urinary phenol concentrations associated with cord steroid hormone levels and anogenital distance (AGD) in male newborns?
    Full-text · Article · Jan 2016 · Human Reproduction
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    • "Many previous studies have suggested that BPA has endocrine disruptor effects. For example, in human BPA appears to impair testosterone production in fetal testis and in rodents fetal and perinatal exposures to environmentally relevant doses of BPA can adversely affect the physiological function of endocrine pancreas, mammary gland and reproductive tract[14]. BPA also disturbs the biology of immune cells and human exposure to BPA seems to play a significant role in the initiation or the enhancement of inflammatory response[15]. Phthalate esters constitute another class of EDCs used often to increase the flexibility and workability of polymers[16]. "
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    ABSTRACT: The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 β and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 μM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations.
    Full-text · Article · Jul 2015 · PLoS ONE
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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.
    Full-text · Article · Jun 2015 · Dose-Response
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