Disruption of thyroid hormone regulated proteins and gene expression by polychlorinated biphenyls, polybrominated diphenyl ethers and new flame retardants in residents of an e-waste region☆
Graphical abstract
Introduction
Once used as additives in electronic products, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) have gradually accumulated in the environment and have been found in humans (Covaci et al., 2003; Sjödin et al., 2003; Hagmar, 2004; Beyer and Biziuk, 2009). As substitutes for PBDEs (Eljarrat and Barceló, 2010; Covaci et al., 2011), new flame retardants (NFRs) have recently been identified in the environment and in humans (Covaci et al., 2011; He et al., 2013; Liu et al., 2014b; Kuang et al., 2016). In China, e-waste dismantling releases PCBs, PBDEs, and NFRs to the surrounding environment (Chen et al., 2009; Robinson, 2009; Gao et al., 2011), potentially exposing dismantling workers and local residents to large quantities of these chemicals (Qu et al., 2007; Zhang et al., 2010; Zheng et al., 2011; Xu et al., 2014; Xu et al., 2015).
PCBs, PBDEs, and NFRs have been revealed to interrupt the equilibrium of thyroid hormone (TH) levels (Giera and Zoeller, 2013). Since TH is crucial for normal growth, development and metabolism (Turakulov et al., 1975), the disruption of TH leads to damage in the normal physiological functions and the overall human health (Miller et al., 2009). Generally, TH levels are disrupted via the response of the hypothalamus-pituitary-thyroid (HPT) axis (Liu et al., 2014a; Thornton et al., 2016). The known mechanisms identified through in-vitro and animal experiments include the prevention of thyroxine carrier proteins from binding TH (Meerts et al., 2000; Hamers et al., 2006; Marchesini et al., 2008; Cao et al., 2010; Audet-Delage et al., 2013), damage to the iodothyronine deiodinases (Gereben et al., 2008; Butt et al., 2011; Dong et al., 2014; Roberts et al., 2015), and competitive binding to the TH receptor (TR) (Kitamura et al., 2008; Miyazaki et al., 2008; Cai et al., 2011). Whether these mechanisms are relevant to interpreting TH disruption from PCBs, PBDEs, and NFRs in humans is still unknown (Thornton et al., 2016). Without knowing these mechanisms, we cannot interpret the inconsistent results in TH disruption reported in previous studies after exposure of humans to these chemicals (Guo et al., 2018b).
Changes in TH-regulated proteins, e.g., upstream and downstream hormones, carrier proteins and receptor proteins, are indicators of TH disrupting mechanisms (Sinha and Yen, 2016). However, as some of them are not distribute in blood but in other organs (Sinha and Yen, 2016), detection of TH-regulated proteins cannot be performed by the use of standard blood sampling methods. To overcome this issue, TH-regulated gene expression in human blood cells was developed (Zheng et al., 2017). Gene expression endpoints have proven to be an effective approach to investigate TH disruption of PBDEs (Fritsche et al., 2005; Ren et al., 2015; Roberts et al., 2015). The understanding of the change in TH-regulated proteins and gene expression in the human body can facilitate the elucidation of the TH disrupting mechanisms, and further interpret more comprehensively the changes in TH levels and the inconsistent results reported in previous studies (Hagmar, 2004).
To better understand the impacts of existing and emerging chemical groups on humans, we selected local residents from an e-waste dismantling site. In addition to PCBs, PBDEs, NFRs, and TH (including triiodethyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4)), TH-regulated proteins and gene expression were analysed. These TH-regulated proteins and gene expression, e.g., thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), thyroglobulin (TG), thyroxine-binding globulin (TBG), TH receptor α (TRα), TH receptor β (TRβ), iodothyronine deiodinase I (ID1), and iodothyronine deiodinase II (ID2), are closely associated with the secretion, synthesis, transport, function and degradation of TH, respectively (Sinha and Yen, 2016). The associations between the levels of PCBs, PBDEs, NFRs and TH-regulated proteins and gene expression were investigated. The findings obtained are important for extending our understanding of TH disrupting mechanisms and focusing our attention on the human health effects exerted by these chemicals.
Section snippets
Sample collection
Two towns in Q city, South China were chosen for the study. One of them had e-waste dismantling activities (exposed region) while the other did not include any industrial or e-waste pollution source (control region). The distance between the two towns is approximately 50 km. The participants with no past history of critical illness were randomly selected from local residents of the two towns (n = 54 for the exposed group and n = 58 for the control group). Details of the sample chosen were
Demographic information and exposure levels
The characteristics of participants are listed in Table 2. Most participants were aged from 46 to 65, about half of them were women. No statistically significant difference was identified for sex, age, incidence of neurological illness and respiratory illness, smoking, serum lipid level, and body mass index (BMI) between the two groups (p > 0.05, Table 2, Table 3). Compared to the participants in the exposed group, more participants in the control group lived far from e-waste factories (Table 2
Conclusion
The results suggest that PCBs, PBDEs, and NFRs have strong binding affinity to TBG, TSH, ID1, and TRα, and high exposures to these chemicals can decrease the levels of TBG, TSH, expression of TRα, but increase expression of ID1. Moreover, our results indicate that a combination of TH disrupting mechanisms is crucial to TH disruption. The present findings improve our understanding of TH disruption, broaden the utilization of gene expression in interpreting disrupting mechanisms, and focus
Acknowledgements
This study was aided financially by the National Key R&D Program of China (2016YFC0207001), National Natural Science Foundation of China (21507013) and Guangzhou Science and Technology Program key projects, China (201707010476).
References (98)
- et al.
Polybrominated diphenyl ethers and sperm quality
Reprod. Toxicol.
(2011) - et al.
Thyroid hormones are associated with exposure to persistent organic pollutants in aging residents of upper Hudson River communities
Int. J. Hyg. Environ. Health
(2014) - et al.
Assessment of polychlorinated biphenyl congeners, thyroid stimulating hormone, and free thyroxine among New York State anglers
Int. J. Hyg. Environ. Health
(2009) - et al.
Impact of co-exposure with butachlor and triadimefon on thyroid endocrine system in larval zebrafish
Exp. Toxicol. Pathol.
(2016) - et al.
Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins
Toxicology
(2010) - et al.
Oral and dermal diflubenzuron exposure causes a hypothalamicepituitaryethyroid (HPT) axis disturbance in the Mongolian racerunner (Eremias argus)
Environ. Pollut.
(2018) - et al.
Pollution characterization and diurnal variation of PBDEs in the atmosphere of an e-waste dismantling region
Environ. Pollut.
(2009) - et al.
Developmental toxicity and thyroid hormone-disrupting effects of 2,4-dichloro-6-nitrophenol in Chinese rare minnow (Gobiocyprisrarus)
Aquat. Toxicol.
(2017) - et al.
Novel brominated flame retardants: a review of their analysis, environmental fate and behaviour
Environ. Int.
(2011) - et al.
Determination of brominated flame retardants, with emphasis on polybrominated diphenyl ethers (PBDEs) in environmental and human samples—a review
Environ. Int.
(2003)
Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish A tool for examining OH-BDE toxicity to early life stages
Aquat. Toxicol.
Effects of ZnO nanoparticles on perfluorooctane sulfonate induced thyroid-disrupting on zebrafish larvae
J. Environ. Sci.
Hormonal activities of new brominated flame retardants
Chemosphere
Interaction between deca-BDE and hepatic deiodinase in a highly PBDE exposed bird
Environ. Res.
Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus)
Environ. Res.
Association between serum polybrominated diphenyl ethers, new flame retardants and thyroid hormone levels for school students near a petrochemical complex, South China
Chemosphere
Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS)
Toxicol. In Vitro
Associations between levels of hydroxylated PCBs and PCBs in serum of pregnant women and blood thyroid hormone levels and body size of neonates
Int. J. Hyg. Environ. Health Perspect.
The human body burden of polybrominated diphenyl ethers and their relationships with thyroid hormones in the general population in Northern China
Sci. Total Environ.
Deiodinases and thyroid metabolism disruption in teleost fish
Environ. Res.
Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines
Aquat. Toxicol.
Association between several persistent organic pollutants and thyroid hormone levels in serum among the pregnant women of Korea
Environ. Int.
Tetrabromobisphenol A and hexabromocyclododecane flame retardants in infant mother paired serum samples, and their relationships with thyroid hormones and environmental factors
Environ. Pollut.
Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture
Toxicology
Concentrations of “legacy” and novel brominated flame retardants in matched samples of UK kitchen and living room/bedroom dust
Chemosphere
Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo
Chemosphere
Association of polybrominated diphenylethers (PBDEs) and hydroxylated metabolites (OH-PBDEs) serum levels with thyroid function in thyroid cancer patients
Environ. Res.
Biosensor discovery of thyroxine transport disrupting chemicals
Toxicol. Appl. Pharmacol.
Associations of birth outcomes with maternal polybrominated diphenyl ethers and thyroid hormones during pregnancy
Environ. Int.
Studies on thyroid hormone-binding proteins
J. Biol. Chem.
Chapter 126-TRH
Exposure to polybrominated diphenyl ethers among workers at an electronic waste dismantling region in Guangdong, China
Environ. Int.
Hydroxylated polybrominated diphenyl ethers exhibit different activities on thyroid hormone receptors depending on their degree of bromination
Toxicol. Appl. Pharmacol.
E-waste: an assessment of global production and environmental impacts
Sci. Total Environ.
Thyroid hormone receptor isoform selectivity of thyroid hormone disrupting compounds quantified with an in vitro reporter gene assay
Environ. Toxicol. Pharmacol.
A review on human exposure to brominated flame retardants—particularly polybrominated diphenyl ethers
Environ. Int.
Developmental exposure to decabromodiphenyl ether (PBDE 209): effects on thyroid hormone and hepatic enzyme activity in male mouse offspring
Chemosphere
Health risk assessment of exposure to polybrominated diphenyl ethers (PBDEs) contained in residential air particulate and dust in Guangzhou and Hong Kong
Atmos. Environ.
Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province, China
Sci. Total Environ.
Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China
Sci. Total Environ.
Thyroid endocrine disruption in zebrafish larvae following exposure to hexaconazole and tebuconazole
Aquat. Toxicol.
Exposure to DE-71 alters thyroid hormone levels and gene transcription in the hypothalamic–pituitary–thyroid axis of zebrafish larvae
Aquat. Toxicol.
Disruption of thyroid hormone (TH) levels and TH-regulated gene expression by polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and hydroxylated PCBs in e-waste recycling workers
Environ. Int.
Levels and sources of brominated flame retardants in human hair from urban, e-waste, and rural areas in South China
Environ. Pollut.
Tetrabromobisphenol A caused neurodevelopmental toxicity via disrupting thyroid hormones in zebrafish larvae
Chemosphere
Environmental chemicals as thyroid hormone analogues: new studies indicate that thyroid hormone receptors are targets of industrial chemicals?
Mol. Cell. Endocrinol.
Persistent organic pollutants and transthyretin-bound thyroxin in plasma of inuit women of childbearing age
Environ. Sci. Technol.
Environmental fate and global distribution of polychlorinated biphenyls
Rev. Environ. Contam. Toxicol.
Halogenated phenolic contaminants inhibit the in vitro activity of the thyroid regulating deiodinases in human liver
Toxicol. Sci.
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This paper has been recommended for acceptance by Wen Chen.