In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol

Università degli Studi di Siena, Siena, Tuscany, Italy
Reproductive Toxicology (Impact Factor: 3.23). 08/2007; 24(2):199-224. DOI: 10.1016/j.reprotox.2007.06.004
Source: PubMed


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.

Download full-text


Available from: Linda S Birnbaum
    • "An increased free BPA level within the placenta may represent a risk for placenta development as well as for the fetus, due to BPA transfer across the feto-maternal barrier (Corbel et al., 2014; Morck et al., 2010). Despite the numerous scientific evidence indicating BPA reproductive and developmental toxicity both in rodents and humans through its endocrine disrupting activity (Richter et al., 2007; Rubin, 2011), studies investigating BPA effects in placenta are rather limited ; however, a few studies on mice show that placenta may be affected during both early and late pregnancy. Subcutaneous administration of 10 mg kg À1 day À1 from gestation day (GD) 0 to 7 altered the development of decidua basalis and trophoblastic layers during implantation (Tachibana et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bisphenol A (BPA) is a widespread endocrine disrupter mainly used in food contact plastics. Much evidence supports the adverse effects of BPA, particularly on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg kg(-1) (BPA50) body weight day(-1) of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in the absence of glycogen accumulation and reduction of the spongiotrophoblast layer. In addition, BPA05 induced glycogen depletion as well as significant nuclear accumulation of β-catenin in trophoblasts of labyrinthine and spongiotrophoblast layers, supporting the activation of the Wnt/β-catenin pathway. Transcriptomic analysis indicated that BPA05 promoted and BPA50 inhibited blood vessel development and branching; morphologically, maternal vessels were narrower in BPA05 placentas, whereas embryonic and maternal vessels were irregularly dilated in the labyrinth of BPA50 placentas. Quantitative polymerase chain reaction evidenced an estrogen receptor β induction by BPA50, which did not correspond to downstream genes activation; indeed, the transcription factor binding sites analysis supported the AhR/Arnt complex as regulator of BPA50-modulated genes. Conversely, Creb appeared as the main transcription factor regulating BPA05-modulated genes. Embryonic structures (head, forelimb) showed divergent perturbations upon BPA05 or BPA50 exposure, potentially related to unbalanced embryonic nutrition and/or to modulation of genes involved in embryo development. Our findings support placenta as an important target of BPA, even at environmentally relevant dose levels. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Nov 2015 · Journal of Applied Toxicology
  • Source
    • "Overall, the variation of ER expression levels in the 2 sexes affects the physiological dimorphism in nuclear morphology and functions (Cao et al. 2014; Rebuli et al. 2014, and the section below). In some cases, this results in a male showing a more feminine phenotype and vice versa, while in other cases the loss of dimorphism is due to a change only in 1 of the 2 sexes (see Richter et al. 2007 and below for further references). Sometimes, the observed outcomes are not completely reproduced by the exposure to estrogens (Rebuli et al. 2014), suggesting that BPA does not act only as estrogen pure agonist on some parameters. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "A large number of them have demonstrated deleterious effects below the established reference dose. These effects include among others alteration of mammary gland development, behavioral effects, abnormalities in the prostate growth, alterations of sexual maturation, altered immune system function , detrimental effects on glucose homeostasis and insulin sensitivity, and so on (vom Saal & Hughes, 2005; Richter et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity and type 2 diabetes mellitus (T2DM) are the most common metabolic disorders, with prevalence rates that are reaching epidemic proportions. Both are complex conditions affecting virtually all ages and with serious health consequences. The underlying cause of the problem is still puzzling, but both genetic and environmental factors including unhealthy diet, sedentary lifestyle, or the exposure to some environmental endocrine disrupting chemicals (EDCs) are thought to have a causal influence. In addition, the impact of early environment has recently emerged as an important factor responsible for the increased propensity to develop adult-onset metabolic disease. Suboptimal maternal nutrition during critical windows in fetal development is the most commonly studied factor affecting early programming of obesity and T2DM. In recent years, increasing experimental evidence shows that exposure to EDCs could also account for this phenomenon. In the present review, we will overview the most relevant findings that confirm the critical role of bisphenol-A, one of the most widespread EDCs, in the development of metabolic disorders.
    Full-text · Article · Jun 2015 · Dose-Response
Show more