Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates

Abstract

Exposure measurements from several countries indicate that humans are routinely exposed to low levels of bisphenol A (BPA), a synthetic xenoestrogen widely used in the production of polycarbonate plastics. There is considerable debate about whether this exposure represents an environmental risk, based on reports that BPA interferes with the development of many organs and that it may alter cognitive functions and mood. Consistent with these reports, we have previously demonstrated that BPA antagonizes spine synapse formation induced by estrogens and testosterone in limbic brain areas of gonadectomized female and male rats. An important limitation of these studies, however, is that they were based on rodent animal models, which may not be representative of the effects of human BPA exposure. To address this issue, we examined the influence of continuous BPA administration, at a daily dose equal to the current U.S. Environmental Protection Agency's reference safe daily limit, on estradiol-induced spine synapse formation in the hippocampus and prefrontal cortex of a nonhuman primate model. Our data indicate that even at this relatively low exposure level, BPA completely abolishes the synaptogenic response to estradiol. Because remodeling of spine synapses may play a critical role in cognition and mood, the ability of BPA to interfere with spine synapse formation has profound implications. This study is the first to demonstrate an adverse effect of BPA on the brain in a nonhuman primate model and further amplifies concerns about the widespread use of BPA in medical equipment, and in food preparation and storage. monkey ͉ stereology ͉ synaptic plasticity S ince the 1950s, the synthetic xenoestrogen bisphenol A (BPA) has been used in the manufacture of plastics with a broad range of uses, including dental prostheses and sealants (1), the polycarbonate lining of metal cans used to preserve foods (2), baby bottles (3) and the clear plastic cages used to house laboratory animals (4). BPA also is used as an additive in many products. Its global production rate is Ͼ6 billion pounds per year. Polycarbonate is less durable than commonly believed, because the ester bond linking BPA molecules to the plastic can be hydrolyzed. With the rate of hydrolysis increasing dramatically under both acidic and basic conditions, and at elevated temperatures, BPA leaches out of polycarbonate containers into food and beverages under normal conditions of use (3-5). As a result, exposure measurement data from several countries, including the United States, indicate that humans are widely exposed to low levels of BPA on a continuous basis (6).There is considerable debate about whether this exposure represents an environmental risk, based mostly on the fact that some hormonally active chemicals exhibit radically different potencies in different bioassay systems, making it difficult to assess their potential adverse effects (7). For example, in a two-generation trial in rats, BPA was reported to not induce significant reproductive abnormalities at ...

Concentration of bisphenol A in thermal paper

“…Both the European Union (EU) (3) and the US National Toxicology Program (NTP) (2) have recently released lengthy reports devoted to BPA which reference hundreds of studies on BPA's hazard potential and exposure routes. Adverse effects associated with exposure to BPA have been reported in a wide range of vertebrate species from fish (4) to rodents (reviewed in 5) to primates (6) and humans (7Á10). These effects suggest but do not prove that BPA is implicated in a wide array of human health conditions, including heart disease (7,8), Type 2 diabetes (7), breast cancer (11), prostate cancer (12), infertility (13), and neurodevelopmental disorders, including attention deficit hyperactivity disorder (14).…”

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

“…The U.S. Environmental Protection Agency (EPA) has defined EDCs as exogenous agents that can interfere with the synthesis, metabolism and action of endogenous hormones (Kavlock et al, 1996). With the benefit of hindsight, the ED effects of environmental chemical contaminants have been shown to impose long-term effect on animal health and development (Anway et al, 2005;Dolinoy et al, 2007;Leranth et al, 2008). Although the regulation on the ''hormonal growth-promoting'' agents in food producing animals has been enforced (Stephany, 2010), the major focus is on the testing of exogenous estrogenic chemicals (Stokes, 2004).…”

Reply to Mathews: Misplaced focus on experimental detail

“…These findings predicted that BPA would be related to diabetes and cardiovascular disease in adults (5). There are thus potentially many non-oral sources of BPA exposure, which has led to the suggestion that the best approach to model continuous exposure of humans to BPA is administration via a continuousrelease capsule, such as that used in our study (6). There is an extensive body of evidence that led the U.S. National Toxicology Program and experts from a National Institutes of Health conference on BPA (3) to express concern that BPA causes damage to the brain in animals and thus is likely to pose a threat to humans.…”