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

https://doi.org/10.1016/j.envpol.2019.07.093Get rights and content

Highlights

  • PCBs, PBDEs, and NFRs disrupted some TH-regulated proteins and gene expression.

  • Levels of TBG, TSH and expression of ID1, TRα were different between the two groups.

  • The disruption on TH-regulated proteins and gene expression may do harm to health.

  • The overall effects on TH depend on a combination of multiple disrupting mechanisms.

Abstract

Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and new flame retardants (NFRs) are known thyroid hormone (TH) disruptors, but their disrupting mechanisms in humans are not completely understood. In this study, we aimed to explore the disrupting mechanisms of the aforementioned chemicals via examining TH-regulated proteins and gene expression in human serum. Adult participants from an e-waste dismantling (exposed group) and a control region (control group) in South China provided blood samples for the research. Some compounds of PCBs, PBDEs, and NFRs showed strong binding affinity to the thyroid-stimulating hormone (TSH), thyroglobulin, thyroxine-binding globulin (TBG), gene expression of TH receptor α (TRα) and β, and iodothyronine deiodinase I (ID1). The highly exposed individuals had lower levels of TBG, TSH, and expression of TRα, but higher expression of ID1 than those of the control group. The disruption of TH-regulated proteins and gene expression suggested the exertion of different and, at times, even contradictory effects on TH disruption. However, no statistically significant difference was found in the TH levels between the exposed and the control group, implying that the TH disruption induced by these chemicals depends on the combined influence of multiple mechanisms. Gene expression appears to be an effective approach for investigations of TH disruption and the potential health effects.

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).

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