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      Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

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          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. Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728

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          In vivo effects of bisphenol A in laboratory rodent studies.

          Concern is mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical used in synthesis of plastics. We have reviewed the growing literature on effects of low doses of BPA, below 50 mg/(kg day), in laboratory exposures with mammalian model organisms. Many, but not all, effects of BPA are similar to effects seen in response to the model estrogens diethylstilbestrol and ethinylestradiol. For most effects, the potency of BPA is approximately 10-1000-fold less than that of diethylstilbestrol or ethinylestradiol. Based on our review of the literature, a consensus was reached regarding our level of confidence that particular outcomes occur in response to low dose BPA exposure. We are confident that adult exposure to BPA affects the male reproductive tract, and that long lasting, organizational effects in response to developmental exposure to BPA occur in the brain, the male reproductive system, and metabolic processes. We consider it likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system, and that developmental effects occur in the female reproductive system.
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            Prenatal Phenol and Phthalate Exposures and Birth Outcomes

            Background Many phthalates and phenols are hormonally active and are suspected to alter the course of development. Objective We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. Methods We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. Results Median urinary concentrations were > 10 μg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07–1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (−210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71–348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. Conclusions We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.
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              Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure.

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                Author and article information

                Journal
                Environmental Health Perspectives
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                August 2014
                August 2014
                : 122
                : 8
                : 775-786
                Affiliations
                [1 ]Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
                [2 ]School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
                [3 ]Department of Urology, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA
                [4 ]Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, USA
                [5 ]Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
                [6 ]Department of Pediatrics,
                [7 ]Department of Obstetrics and Gynecology,
                [8 ]Department of Molecular and Integrative Physiology, and
                [9 ]Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA
                [10 ]Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, New Haven, Connecticut, USA
                [11 ]Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
                [12 ]Department of Obstetrics and Gynecology, and
                [13 ]California National Primate Research Center, University of California, Davis, Davis, California USA
                Article
                10.1289/ehp.1307728
                c5c6c011-8766-4d9f-9425-28bd6375c700
                © 2014
                History

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