Bisphenol A stifles thyroid hormone and slows frog development.
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Heimeier, R, B Das, DR Buchholz and YB Shi. 2009. The xenoestrogen bisphenol A inhibits postembryonic vertebrate development by antagonizing gene regulation by thyroid hormone. Endocrinology doi:10.1210/en.2008-1503. |
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| Low levels of BPA similar to levels found in babies slowed tadpole development by messing with thyroid hormone signals. |
A new study reveals that by interfering with thyroid hormone, exposure to low levels of bisphenol A (BPA) slows the rate at which tadpoles develop into frogs. Thyroid signals are necessary both for normal frog metamorphosis and for human development. In these experiments, exposure levels similar to those found in human infants kept certain genes from turning on, thus delaying tadpole development. Analyzing tadpole metamorphosis is an ideal model system for observing the consequences of BPA exposure on the thyroid system, say the authors.
Context
Bisphenol A (BPA) is added to plastic to make it more durable and help it keep its shape. It is mostly found in hard polycarbonate plastics and epoxy resins. Products such as polycarbonate water and baby bottles, medical devices (tubes), toys, compact discs, sports equipment and plastic pipes can contain BPA.
Because of its use in so many everyday products, humans are constantly exposed to low levels of the chemical. The Center for Disease Control and Prevention has reported that BPA is found in 93 percent of Americans (Calafat et al. 2008). Recent studies suggest that levels may be higher in children than in adults (Edgington and Ritter 2008).
The widespread use of BPA in common plastics materials, particularly those used by infants, has raised questions about its safety. Prior animal research suggests possible adverse effects on behavior, prostate development and reproduction (Maffini et al. 2006).
BPA can act like an estrogen hormone and interfere with natural estrogens that control reproduction. Very little is known about its effects on other hormone systems, including the thyroid.
Thyroid hormones play a central role in all vertebrate development, including frogs and primates. The two most active types are called T3 and T4. Like most hormones, thyroid hormones work by binding to a thyroid hormone receptor and activating gene transcription.
T3 is essential for frogs to develop normally, a process called metamorphosis. It is also an important regulator of human brain development and metabolism throughout life.
Thyroid hormones are unique among hormones because they contain iodine. Iodine deficiency and genetic disorders that disrupt thyroid hormone function can cause neurological disorders ranging from ADHD to mental retardation. Thyroid hormone deficiency, particularly during specific critical periods in human fetal development, leads to irreversible mental retardation.
If BPA disrupts the thyroid hormone system in humans, then exposure to common household items containing BPA could have profound consequences on brain development, behavior and metabolic function.
Researchers from the National Institutes of Health used frog tadpoles to study how BPA alters thyroid hormone during development and affects genes activated by T3.
Tadpoles offer a good system to study BPA's effects on thyroid hormone function. That is because thyroid hormones are necessary for both normal human fetal development and amphibian metamorphosis. Further, unlike in people, frog development is minimally affected by sex hormones, such as estrogen. Hence, researches could tease out the consequences of BPA exposure on thyroid hormone without interference from estrogens.
The authors exposed groups of growing tadpoles to either 0.1 or 10 micromolar BPA with and without T3 hormone for 21 days during metamorphosis. Comparisons were made among untreated tadpoles and tadpoles treated with BPA alone, T3 alone and a combination of T3 and BPA.
These low BPA doses have been shown to interfere with T3 hormone and are relevant to exposures in human infants.
The tadpoles were photographed every three days to determine changes to the structure of their intestine. The organ depends on T3 to develop properly and is a hallmark of the metamorphic change from tadpole to frog.
The researchers also looked at genes that are regulated by the thyroid hormone. They measured the effects of BPA on gene regulation at the early stages of development in frog eggs and later during gut development.
Overall, both doses of BPA affected metamorposis and gene expression that is controlled by T3 hormone.
Metamorphosis took longer than normal in the animals treated with the BPA and T3 hormone together. The higher the dose of BPA, the slower the tadpoles changed. Similarily, the combination delayed normal tissue changes in the intestine, prolonging metamorphosis.
BPA altered the expression of many genes known to be turned on by thyroid hormone in frog eggs and tadpoles. The chemical did this by silencing – or inhibiting the expression of – a number of genes that govern normal tadpole gut development.
BPA alone also altered T3 gene expression. However, no associated changes to metamorphosis or intestinal development were observed, making it difficult to conclude the importance of the changes.
BPA is a potent inhibitor of thyroid hormone, which directs development in both amphibians and people. In this study, BPA suppressed a subset of important genes controlled by T3 that contribute to proper development in frogs.
The study confirms past research showing BPA interferes with thyroid hormone (Goto et al. 2006, Iwamuro et al. 2006). It is also consistent with studies that show BPA slows and alters development.
However, it takes an important step forward by identifying more precisely how BPA acts on the thyroid hormone system. The novel approach taken by this research team provides solid evidence that BPA interferes primarily with thyroid hormone signaling – rather than estrogen signals – to alter gene expression and amphibian metamorphosis.
The model system could represent how BPA might impact human development, too. T3 is important for both people and frogs. T3 governs similar developmental milestones that occur during frog metamorphosis and in late-stage human pregnancies. Thus, BPA has the potential to affect genes that are regulated by thyroid hormone during human development. According to the authors, "our results argue that BPA represents a serious risk to human development through disruption of T3 signaling pathways."
The findings also support prior animal studies that find exposure to BPA during development can produce permanent effects that may impact health. In light of these findings, BPA exposure while in the womb and as newborns could pose a longterm health risk by altering development of brain and reproductive systems that are directed by thyroid hormone.
BPA's safety is garnering attention from regulatory agencies and governments. A 2008 report by the National Toxicological Program expressed concern about potential negative effects of BPA on the development of the human brain and reproductive system. At about the same time, the Food and Drug Administration determined that no action is necessary to regulate BPA exposure levels in children. This decision will be revisited sometime later this year.
Minnesota became the first US state to ban BPA earlier this month. Canada banned BPA use in baby bottles late last year. In March, the six largest manufacturers of plastic baby bottles in the US announced that they will stop selling bottles containing BPA. Water bottle manufacturers are also phasing the chemical out of their products. In April, one of the US manufacturers of BPA, Sunoco, announced it would not sell BPA to companies unless they guaranteed it would not be used in products intended for infants and children.
ResourcesBisphenol A. National Toxicology Program. National Institute of Environmental Health Sciences (PDF). Calafat, AM, X Ye, LY Wong, JA Reidy and LL Needham. 2008. Exposure of the US population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environmental Health Perspectives 116(1):39-44. Edginton, A and L Ritter. 2009. Predicting plasma concentrations of Bisphenol A in young children (< two years) following typical feeding schedules using a physiologically-based toxicokinetic model. Environmental Health Perspectives 117:645–652. Frog metamorphosis. tooter4kids Web site. Goto, Y, S Kitanura, K Kashiwagi, K Oofusa, O Tooi, K Yoshizato, J Sato, S Ohta and A Kashiwagi. 2006. Suppression of amphibian metamorphosis by bisphenol A and related chemical substances. Journal of Health Science 52:160-168. Iwamuro, S, M Yamada, M Kato and S Kikuyama. 2006. Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid hormone receptor alpha and beta and downregulation of retinoid X receptor gamma in Xenopus tail culture. Life Sciences 79:2165-2171. Maffini, MV, BS Rubin, C Sonnenschein and AM Soto. 2006. Endocrine disruptors and reproductive health: the case of bisphenol-A. Molecular and Cellular Endocrinology 254-255:179-186. Rust, S. Babies carry more BPA, scientist group agrees. Milwaukee Journal Sentinel, April 11, 2009. Since You Asked - Bisphenol A. Questions and answers about the National Toxicology Program's evaluation of BPA. National Institute of Environmental Health Science. |
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