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Journal ArticleDOI

Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility.

TL;DR: Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration, and this point to the importance of seminal plasma in BPA research.
Abstract: The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration.

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Journal ArticleDOI
TL;DR: The underlying mechanisms of BPA-induced multi-organ toxicity were well summarized, involving the receptor pathways, disruption of neuroendocrine system, inhibition of enzymes, modulation of immune and inflammatory responses, as well as genotoxic and epigenetic mechanisms.

321 citations

Journal ArticleDOI
TL;DR: This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.
Abstract: Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.

142 citations


Cites background from "Differences in bisphenol A and estr..."

  • ...These defects are paralleled by higher BPA levels in urine and plasma samples [88]....

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Journal ArticleDOI
TL;DR: The data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps, and may negatively contribute to the final state of sperm quality.

112 citations

Journal ArticleDOI
TL;DR: Overall, the evidence supporting an association between BPA exposure and adverse male reproductive health outcomes in humans remains limited and inconclusive.

100 citations

Journal ArticleDOI
TL;DR: In this paper, a review of the current research data on BPA, providing an overview of the findings obtained from studies in animal and human models, as well as on its supposed mechanisms of action.
Abstract: Among the factors causing male infertility, one of the most debated is the exposure to environmental contaminants. Recently, the chemical compound Bisphenol A (BPA) has drawn attention from the reproductive science community, due to its ubiquitous presence in day-to-day life. Its toxic action appears to mainly affect the male reproductive system, directly impacting male fertility. The purpose of this review is to investigate current research data on BPA, providing an overview of the findings obtained from studies in animal and human models, as well as on its supposed mechanisms of action. A clear understanding of BPA action mechanisms, as well as the presumed risks deriving from its exposure, is becoming crucial to preserve male fertility. The development and validation of methodologies to detect BPA toxic effects on reproductive organs can provide greater awareness of the potential threat that this chemical represents.

100 citations

References
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Journal ArticleDOI
TL;DR: This study provides a basis for prioritizing toxicology and exposure research for individual EDCs and mixtures and provides new tools for exposure assessment in health studies.
Abstract: Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread consumer uses, yet little is known about indoor exposure. We sampled indoor air and dust in 120 homes, analyzing for 89 organic chemicals identified as EDCs. Fifty-two compounds were detected in air and 66 were detected in dust. These are the first reported measures in residential environments for over 30 of the compounds, including several detected at the highest concentrations. The number of compounds detected per home ranged from 13 to 28 in air and from 6 to 42 in dust. The most abundant compounds in air included phthalates (plasticizers, emulsifiers), o-phenylphenol (disinfectant), 4-nonylphenol (detergent metabolite), and 4-tert-butylphenol (adhesive) with typical concentrations in the range of 50−1500 ng/m3. The penta- and tetrabrominated diphenyl ethers (flame retardants) were frequently detected in dust, and 2,3-dibromo-1-propanol, the carcinogenic intermediate of a flame retardant banned in 1977, was detected in air an...

966 citations


"Differences in bisphenol A and estr..." refers background in this paper

  • ...Further minor ways of penetrating into the body are through the skin (e.g. contact with thermal receipts) (Ehrlich et al. 2014, Liao and Kannan 2011) or inhalation (e.g. cigarette smoke or dust) (Braun et al. 2011, He et al. 2009, Inoue et al. 2006, Rudel et al. 2003)....

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Journal ArticleDOI
TL;DR: The efficient glucuronidation of bisphenol A and the rapid excretion of the formed glucuronide result in a low body burden of the estrogenic bispenol A in humans following oral absorption of low doses.
Abstract: Bisphenol A is a widely used industrial chemical with many potential sources of human exposure. Bisphenol A is a weak estrogen and has been implicated as an "endocrine disruptor". This term is used for a variety of chemicals encountered in the environment which have estrogenic activity. It has been postulated that human exposure to these chemicals may elicit unwanted estrogenic effects in humans such as reduced fertility, altered development and cancer. Up to now the body burden of bisphenol A in humans is unknown. Therefore, we investigated the metabolism and toxicokinetics of bisphenol A in humans exposed to low doses since systemic bioavailability has a major influence on possible estrogenic effects in vivo. Human subjects (three males and three females, and four males for detailed description of blood kinetics) were administered d(16)-bisphenol A (5 mg). Blood and urine samples were taken in intervals (up to 96 h), metabolites formed were identified by GC/MS and LC-MS/MS and quantified by GC/MS-NCI and LC-MS/MS. d(16)-Bisphenol A glucuronide was the only metabolite of d(16)-bisphenol A detected in urine and blood samples, and concentrations of free d(16)-bisphenol A were below the limit of detection both in urine (6 nM) and blood samples (10 nM). d(16)-Bisphenol A glucuronide was cleared from human blood and excreted with urine with terminal half-lives of less than 6 h; the applied doses were completely recovered in urine as d(16)-bisphenol A glucuronide. Maximum blood levels of d(16)-bisphenol A glucuronide (approximately 800 nM) were measured 80 min after oral administration of d(16)-bisphenol A (5 mg). The obtained data indicate major species differences in the disposition of bisphenol A. Enterohepatic circulation of bisphenol A glucuronide in rats results in a slow rate of excretion, whereas bisphenol A is rapidly conjugated and excreted by humans due to the absence of enterohepatic circulation. The efficient glucuronidation of bisphenol A and the rapid excretion of the formed glucuronide result in a low body burden of the estrogenic bisphenol A in humans following oral absorption of low doses.

882 citations


"Differences in bisphenol A and estr..." refers background in this paper

  • ...It has generally been thought that BPA is rapidly metabolized in the liver and excreted in the urine within hours (Volkel et al. 2002, 2005)....

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Journal ArticleDOI
TL;DR: This review is a detailed review of published studies that have focused on the mechanistic basis of BPA action in diverse experimental models and an assessment of the strength of the evidence regarding the published BPA research.

850 citations

Journal ArticleDOI
TL;DR: Four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses.
Abstract: Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted.

849 citations


"Differences in bisphenol A and estr..." refers background in this paper

  • ...BPA is a weak estrogen when considering its binding activities to the estrogen receptor (ER) (Welshons et al. 2003)....

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Journal ArticleDOI
TL;DR: The results suggest that BPA could displace T(3) from the TR and recruit a transcriptional repressor, resulting in gene suppression, the first report that B PA can antagonize T( 3) action at the transcriptional level.
Abstract: Bisphenol A (BPA), a monomer of polycarbonate plastics, has been shown to possess estrogenic properties and act as an agonist for the estrogen receptors. Although an epidemiologically based investigation has suggested that some chemicals could disrupt thyroid function in animals, the effects on thyroid hormone receptors (TRs) are unknown. We show here that BPA inhibits TR-mediated transcription by acting as an antagonist. In the transient gene expression experiments, BPA suppressed transcriptional activity that is stimulated by thyroid hormone (T3) in a dose-dependent manner. The inhibitory effects were observed in the presence of physiological concentrations of T3. In contrast, in the case of negatively regulated TSH promoter, BPA activated the gene transcription that is suppressed by T3. To elucidate possible mechanisms of the antagonistic action of BPA, the effects on T3 binding and cofactor interaction with TR were examined. The Ki value for BPA was 200 M when assessed by inhibition of [ 125 I]T3 binding to rat hepatic nuclear TRs. In a mammalian two-hybrid assay, BPA recruited the nuclear corepressor to the TR. These results suggest that BPA could displace T3 from the TR and recruit a transcriptional repressor, resulting in gene suppression. This is the first report that BPA can antagonize T3 action at the transcriptional level. BPA may disrupt the function of various types of nuclear hormone receptors and their cofactors to disturb our internal hormonal environment. (J Clin Endocrinol Metab 87: 5185–5190, 2002)

717 citations


"Differences in bisphenol A and estr..." refers background in this paper

  • ...…the estrogen related receptor (Delfosse et al. 2014, Okada et al. 2008), androgen receptor (Lee et al. 2003, Teng et al. 2013), thyroid receptor (Moriyama et al. 2002), glucocorticoid receptor (Sargis et al. 2010), peroxisome proliferator activated receptor γ (PPARγ) (Pereira-Fernandes et al.…...

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Does estrogen kill sperm?

Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration.