Urinary Bisphenol A Concentrations and Cytochrome P450 19 A1 (Cyp19) Gene Expression in Ovarian Granulosa Cells: An in vivo Human Study.
ABSTRACT Exposure to bisphenol A (BPA), a chemical widely used in consumer products, has been associated with in vitro Cyp19 gene expression.
To evaluate an in vivo human model of Cyp19 gene expression in granulosa cells.
A subset of an ongoing prospective cohort study of women undergoing in vitro fertilization (IVF) at Massachusetts General Hospital.
Mixed effect models were used to evaluate the association of urinary BPA concentrations with granulosa cell Cyp19 mRNA expression.
In 61 women undergoing 76 IVF cycles, adjusted changes in mean Cyp19 expression (β estimate (95% CI)) for quartiles 2,3 and 4 as compared to the lowest quartile were: -0.97 (-2.22, 0.28); -0.97 (-2.18, 0.24) and -0.38 (-1.58, 0.82).
An in vivo model for evaluation of Cyp19 gene expression was developed for use in epidemiologic studies. In this pilot study, we found no statistically significant linear association between urinary BPA concentrations and Cyp19 expression.
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- "A case–control study by Kandaraki et al. (2011) showed that BPA was associated with increased testosterone and androstenedione levels in women with polycystic ovary syndrome (PCOS). In a study of 60 women under going IVF, Ehrlich et al. (2013) found that urinary BPA concentrations were not associated with a negative linear dose–response in the expression of the steroido genic enzyme Cyp19 in granulosa cells collected at the time of oocyte retrieval, but instead were associated with a suggested non monotonic dose–response. Conversely, BPA was not associated with estradiol or testosterone levels in women in the INChianti study, a prospective, population-based study of adults living in Chianti, Italy (Galloway et al. 2010). "
ABSTRACT: Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction. Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action. Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction. Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development. Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.Environmental Health Perspectives 06/2014; 122(8). DOI:10.1289/ehp.1307728 · 7.98 Impact Factor
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ABSTRACT: Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids and estrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high body mass index, exposure to estrogens or synthetic compounds such as tamoxifen. Studies in cell and animal models have provided evidence that many EDC can bind estrogen receptors and highlighted early life exposure as a window of risk for adverse life-long effects on the reproductive system. In women the most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol (DES). Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence to date.Endocrine Related Cancer 10/2013; 21(2). DOI:10.1530/ERC-13-0342 · 4.91 Impact Factor
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ABSTRACT: In this work, we utilized the nonionic fluorosurfactant-capped gold nanoparticles (GNPs) as a novel chemiluminescence (CL) probe for the determination of trace bisphenol A. Bisphenol A can induce a sharp decrease in CL intensity from the GNP-Co(2+)-peroxymonocarbonate (HCO4(-)) system. Under the selected experimental conditions, a linear relationship was obtained between the CL intensity and the logarithm of concentration of bisphenol A in the range of 0.05-50μM (R(2)=0.9936), and the detection limit at a signal-to-noise ratio of 3 for bisphenol A was 10nM. The applicability of the proposed method has been validated by determining bisphenol A in real polycarbonate samples with satisfactory results. The recoveries for bisphenol A in spiked samples were found to be between 94.4% and 105.0%. The relative standard deviation (RSD) for 12 repeated measurements of 0.5μM bisphenol A was 2.2%. The proposed method described herein was simple, selective and obviated the need of extensive sample pretreatment.Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy 07/2014; 128:393–397. DOI:10.1016/j.saa.2014.02.153 · 2.13 Impact Factor