Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid hormone receptor α and β and down-regulation of retinoid X receptor γ in Xenopus tail culture

Department of Biology, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Life Sciences (Impact Factor: 2.7). 12/2006; 79(23):2165-71. DOI: 10.1016/j.lfs.2006.07.013
Source: PubMed


We investigated effects of different concentrations (10(-7) - 10(-5) M) of bisphenol A (BPA), which is known as an estrogenic and anti-thyroid hormonal endocrine disrupter, on the expression of thyroid hormone receptor (TR) alpha and beta and retinoid X receptor (RXR) gamma mRNA in tails of stage 52-54 Xenopus tadpoles in organ culture in the presence or absence of different concentrations of triiodo-thyronine (T(3)). In the absence of T(3), BPA at any concentration examined did not show remarkable effects on tail length but blocked 10(-7) M T(3)-induced tail resorption in a concentration-dependent manner. Semi-quantitative analyses of TRalpha and TRbeta mRNAs by RT-PCR in the tail specimens indicated that BPA shows an apparent antagonistic effect towards the receptors and reduced their mRNA levels relative to controls. When administered together with 10(-7) M T(3), the antagonistic effects of BPA were detected more clearly and dose-dependently. While BPA prevented the autoinduction of both TRalpha and TRbeta genes by T(3), the effect was less marked on TRalpha than on TRbeta. BPA also moderately suppressed RXRgamma gene expression. Gene expression of RXRgamma, a partner for heterodimer formation of TRs, was supressed by T(3) alone and also by BPA alone, but no additive effects were observed so far as studied. The present study indicates that a relatively low concentration of BPA, 10(-7) M, as compared with those examined previously (10(-5) to 10(-4) M) by us and other investigators, acts as an antagonist of T(3) through suppression of TRalpha and TRbeta gene expression in Xenopus tail in culture.

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    • "In vivo studies on aquatic species have reported inhibitory effects of TBBPA on Rana pipiens ( Iwamuro , Yamada , Kato , & Kikuyama , 2006 ) and on X . laevis TH signaling ( Fini et al . "
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    ABSTRACT: Classically, thyroid hormones (THs) have been primarily associated with postembryonic development (Tata, 1968), notably metamorphosis in anuran amphibians and flat fish. This period is parallel to the perinatal period in man and many marked developmental transitions in other species. As amply described in other chapters, metamorphosis is characterized by a peak of thyroxine (T(4)) and triiodothyronine (T(3)) that is synchronous with the metamorphic climax. In contrast, the developmental period that characterizes embryonic development prior to the significant production of TH by the endogenous thyroid gland has received little attention. Furthermore, the prevailing concepts of TH physiology during this period have been framed by two observations in amphibians and mammals: first, TRs are expressed, while circulating TH levels are much lower than those during metamorphosis and, second, extrapolating from the knowledge largely obtained from in vitro models, in the absence of TH, the aporeceptor represses target gene transcription during premetamorphic development. We propose to revisit both concepts in the light of accumulating data, first, on TH availability both in eggs and in embryos and, second, on the increasing knowledge of the complexity of TR and TH control of transcription.
    Full-text · Article · Jan 2013 · Current Topics in Developmental Biology
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    • "BPA is a TR antagonist in transient transfection assays in mammalian cells and BPA exposure of rats during pregnancy causes an increase in serum thyroid hormone concentration [27-29]. BPA acts as a TR antagonist in a tail culture assay in Xenopus [30]. Further, BPA inhibits T3-dependent responses in an in vivo Xenopus embryo TH sensitive gene transcription reporter assay [31]. "
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    ABSTRACT: The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and Xenopus models. We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in Xenopus embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na+/K+ ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na+/K+ ATPase with ouabain can rescue the BPA-induced otolith phenotype. The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor.
    Full-text · Article · Jan 2011 · BMC Developmental Biology
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    • "Phthalates inhibit estrogen receptors in fish (Jobling et al., 1995); phthalates bioaccumulate in the aquatic plant Elodea canadensis, the clam Sphaeriun striatinum, and the water flea Daphnia magna (Metcalf et al., 1973). Bisphenol A Building block of polycarbonate plastics, epoxy lining of food and beverage cans, also used in dental sealants Estrogen, thyroid possible Male brown trout exposed to BPA at concentrations of 1.75, 2.40, 5.00 μg/L had reduced sperm quality, and females exhibited reduced or inhibited ovulation (Lahnsteiner et al., 2005); BPA exposure impacts tadpole tail development in the frog species, Xenopus (Iwamuro et al., 2006); BPA bioaccumulates in spotted halibut, Varaspar variegates, with exposures of 70 μg/L (Lee et al., 2004). Triclosan Antibacterial agent in liquid hand soap, dish soap, toothpaste, cutting boards, countertops and many other consumer products; pesticide Thyroid, androgen, estrogen Triclosan, in combination with natural thyroid hormones, triggered increased rates of metamorphosis and tail fin gene expression in the North American bullfrog, Rana catesbeiana, at 0.15 μg/L (Veldhoen et al., 2006); triclosan produced weak androgenic effects in Japanese medaka fry (Oryzias latipes) (Foran et al., 2000), and weak anti-estrogenic effects in male South African clawed frogs (Xenopus laevis) (Matsumura et al., 2005); triclosan produces chronic or acute toxicity in aquatic species (e.g. "
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    ABSTRACT: Synthetic endocrine-disrupting chemicals (EDCs) have been found in surface waters throughout the United States, and are known to enter waterways via discharge from wastewater treatment plants (WWTPs). Studies addressing EDCs in wastewater do not examine their specific sources upstream of WWTPs. Presented here are results of a pilot study of potential sources of selected EDCs within an urban wastewater service area. Twenty-one wastewater samples were collected from a range of sites, including 16 residential, commercial, or industrial samples, and five samples from influent and effluent streams at the WWTP. Samples were analyzed for the following known and suspected EDCs: five phthalates, bisphenol A (BPA), triclosan, 4-nonylphenol (NP), and tris(2-chloroethyl) phosphate (TCEP), using well-established methods (EPA 625 and USGS O-1433-01). Twenty of 21 samples contained at least one EDC. Phthalates were widely detected; one or more phthalate compound was identified in 19 of 21 samples. Measurement of two phthalates in a field blank sample suggests that the accuracy of sample detections for these two compounds may be compromised by background contamination. Triclosan was detected in nine samples, BPA in five samples, and TCEP in four samples; NP was not detected. The results of this and future source-specific studies may be used to develop targeted pollution prevention strategies to reduce levels of EDCs in wastewater.
    Full-text · Article · Sep 2008 · Science of The Total Environment
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