Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs in human serum from Shanghai, China: a study on their presence and correlations

Xu, Bentuo; Wu, Minghong; Wang, Mingnan; Pan, Chenyuan; Qiu, Wenhui; Tang, Liang; Xu, Gang

doi:10.1007/s11356-017-0709-4

Cited by 32 publications

(10 citation statements)

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“…Similar results were observed in serum among a sample of 137 pregnant women in NC, where BDE47 was strongly correlated to BDE99 (r = 0.80) and BDE100 (r = 0.80), yet weaker for BDE153 (r = 0.52) (Stapleton et al, 2011). However, among a serum sample of men and women in Shanghai, China (n = 25), BDE47 was strongly correlated to both BDE100 (r = 0.97) and BDE154 (r = 0.97) (Xu et al, 2018). They also observed a strong correlation between BDE100 and BDE154 (r = 0.99).…”

Section: Discussionmentioning

confidence: 91%

Exploring reproductive associations of serum polybrominated diphenyl ether and hydroxylated brominated diphenyl ether concentrations among women undergoing in vitro fertilization

et al. 2020

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STUDY QUESTION Are serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated brominated diphenyl ethers (OH-BDEs) associated with IVF endpoints? SUMMARY ANSWER Positive associations were observed for BDE153 and several OH-BDEs with IVF endpoints. WHAT IS KNOWN ALREADY PBDEs have been voluntarily phased out of production in the USA and EU due to their persistence and toxicity to humans and ecosystems. PBDEs have been associated with implantation failure among women undergoing IVF, yet some animal studies suggest greater toxicity from their metabolites, OH-BDEs. STUDY DESIGN, SIZE, DURATION We evaluated a subset of 215 women (contributing 330 IVF cycles) enrolled between 2005 and 2016 in a longitudinal cohort based at Massachusetts General Hospital Fertility Center. PARTICIPANTS/MATERIALS, SETTING, METHODS The following PBDEs were quantified: 47, 99, 100, 153 and 154 and the following OH-BDEs: 3-OH-BDE47, 5-OH-BDE47, 6-OH-BDE47 and 4-OH-BDE49. Clinical endpoints of IVF treatments were abstracted from electronic medical records. Associations of log-transformed PBDEs and OH-BDEs with IVF outcomes were assessed using multivariable generalized mixed models and cluster weighted generalized estimating equation models adjusted for lipids, age, BMI, race, year of sample collection, IVF protocol and FSH levels. Outcomes were adjusted to represent a percent change in outcome with an increase equal to the magnitude of the difference between the 75th and 25th percentiles for each specific compound (interquartile range (IQR) increase). MAIN RESULTS AND THE ROLE OF CHANCE Detection frequencies were highest for congeners 47 and 153 (82% ≥ method detection limit (MDL)) and metabolites 3 and 5-OH-BDE47 and 4-OH-BDE49 (92% > MDL). PBDE and OH-BDE geometric mean concentrations declined by up to 80% between participants recruited in 2005 and those recruited in 2016. An IQR increase of BDE153 was associated with an increase in the probability of implantation (relative risk (RR) = 1.26, 95% CI: 1.16, 1.36), clinical pregnancy (RR = 1.32, 95% CI: 1.19, 1.46) and live birth (RR = 1.34; 95% CI: 1.15, 1.54). An IQR increase in 3 and 5-OH-BDE47 was associated with increased probabilities of implantation (RR = 1.52; 95% CI: 1.11, 2.09), clinical pregnancy (RR = 1.66; 95% CI: 1.17, 2.36), and live birth (RR = 1.61; 95% CI: 1.07, 2.40). When models were stratified by race (White (86%)/Other race (14%)), associations remained positive for White women, yet inverse associations were observed for Other race women. An IQR increase in BDE47 was associated with a 46% decreased probability of clinical pregnancy (95% CI: 0.31, 0.95) for Other race women. LIMITATIONS, REASONS FOR CAUTION Despite the long half-lives of PBDEs and OH-BDEs, exposure misclassification is possible for women who underwent multiple treatment cycles over several months or years. It is also possible another medium, such as follicular fluid would be optimal to characterize exposure. We also tested associations for multiple congeners and metabolites with multiple outcomes. WIDER IMPLICATIONS OF THE FINDINGS Detections of serum concentrations of PBDEs and OH-BDEs were highest in the early years of the study and suggests that the phase-out of these compounds has contributed to a decrease in exposure. The negative associations found for PBDEs and IVF outcomes among other race women suggests the potential for racial disparity. Potential racial disparities in PBDE exposure and exploration of alternative flame retardants with reproductive health outcomes should be the focus of future investigations. STUDY FUNDING/COMPETING INTEREST(S) Funding for this research was supported by the National Institutes of Environmental Health Sciences (NIEHS) [R01 ES009718, ES022955, ES000002 and 009718T32ES007069]. The authors have no conflicts of interest.

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Section: Discussionmentioning

confidence: 91%

Exploring reproductive associations of serum polybrominated diphenyl ether and hydroxylated brominated diphenyl ether concentrations among women undergoing in vitro fertilization

et al. 2020

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“…The levels of cord serum PBDEs in our study (23.17 ng/g lipid) were generally lower than those reported in North America (33.32 ng/g lipid in the USA and 93.66 ng/g lipid in Canada) (Chen et al, 2013;Foster et al, 2011). However, they were ve orders of magnitude higher than those reported in serum samples collected during other studies performed on general populations in various areas of China, such as Hong Kong (4.45 ng/g lw; Ho et al, 2015) and Shanghai (2.16 ng/g lw; Xu et al, 2018). The possible reason for the high PBDEs levels in our study might be associated with high amounts of exposure in our study area (Li et al, 2017), which is located near several large-scale BFR production factories.…”

Section: Discussionmentioning

confidence: 57%

DNA Hypermethylation of Brain-Derived Neurotrophic Factor is Associated with High Levels of Polybrominated Diphenyl Ethers in the Cord Serum: A Laizhou Wan Birth Cohort Study From China

Chen¹,

Zhang²,

Zhou³

et al. 2021

Preprint

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Background Recent studies have suggested that in utero exposure to environmental organic pollutants, such polybrominated diphenyl ethers (PBDEs) and bisphenol A may induce epigenetic alterations, specifically by modifying the patterns of DNA methylation. We investigated the relationship between PBDE exposure and BDNF DNA methylation. Methods We measured the levels of eight PBDE congeners in umbilical cord serum samples using gas chromatography/mass spectrometry. Genomic DNA was extracted from whole cord blood samples. The methylation status of the BDNF gene was determined using methylation-specific PCR with primers specific for either methylated or unmethylated alleles. The unconditional logistic regression model was used to investigate the relationship between PBDE levels and BDNF DNA methylation. Results The total PBDE congener level (range) in cord serum samples was 23.17 (4.17–2459.46) ng/g lipid. After adjusting for potential confounders, the incidence of BDNF DNA methylation status may increase when cord serum BDE-28, BDE-47, BDE-99 and BDE-100 levels increased (OR = 3.32, 95% CI: 1.01, 10.85; OR = 7.89, 95% CI: 1.75, 35.66; OR = 7.34, 95% CI: 1.79, 30.09; OR = 3.96, 95% CI: 1.15, 13.68; respectively). Conclusions We found that the levels of BDE-28, -47, -99, and − 100 were positively associated with BDNF DNA hypermethylation. Changes in cord blood BDNF DNA methylation may be a part of the biological pathway underlying in utero PBDE exposure and adverse foetal growth.

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“…Levels for BDE47 in the U.S. population are roughly 3 to 10 times higher than levels in populations from different studies conducted in European countries (Sjodin et al, 2018). A study conducted in China in 2017 quantified BDEs and OH-BDEs in human serum and their findings showed that BDE47 and 6-OH-BDE47 were the congeners present at highest concentrations in the samples studied (Xu et al, 2018).…”

Section: Introductionmentioning

confidence: 71%

Sulfonation and glucuronidation of hydroxylated bromodiphenyl ethers in human liver

2019

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Hydroxylated bromodiphenyl ethers (OH-BDEs) can arise from monooxygenation of anthropogenic BDEs or through natural biosynthetic processes in marine organisms, and several OH-BDEs have been shown to be toxic. OH-BDEs are expected to form sulfate and glucuronide conjugates that are readily excreted, however there is little information on these pathways. We examined the human hepatic glucuronidation and sulfonation of 6-OH-BDE47, 2-OH-BDE68, 4-OH-BDE68 and 2-OH-6'methoxy-BDE68. Human liver microsomes and cytosol were from deidentified female and male donors aged 31 to 75 under an exempt protocol. Recombinant human SULT1A1, 1B1, 1E1 and 2A1 enzymes were prepared from bacterial expression systems. Sulfonation and glucuronidation of each OH-BDE were studied using radiolabeled co-substrates, 3'phosphoadenosine-5'phospho-35 S-sulfate or uridine diphospho-β-D-14 C-glucuronic acid in order to quantify the sulfated or glucuronidated products. The OH-BDEs studied were more efficiently glucuronidated than sulfonated. Of the compounds studied, 2-OH-BDE68 was the most readily conjugated, and exhibited an efficiency (V max /K M ) of glucuronidation of 0.274 ± 0.125 ml/min/mg protein, mean ± S.D., n=3, while that for sulfonation was 0.179 ± 0.030 ml/min/mg protein. For both pathways, all K m values were in the low μM range. Studies with human SULT enzymes showed that sulfonation of these four substrates was readily catalyzed by SULT1B1 and SULT1E1. Much lower activity was found with SULT1A1 and SULT2A1. Assuming that the glucuronide and sulfate conjugates are non-toxic and readily excreted, as is the case for most such conjugates, these studies suggest that OH-BDEs should not accumulate in people to the same extent as the parent BDEs.

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Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs in human serum from Shanghai, China: a study on their presence and correlations

Cited by 32 publications

References 50 publications

Exploring reproductive associations of serum polybrominated diphenyl ether and hydroxylated brominated diphenyl ether concentrations among women undergoing in vitro fertilization

Exploring reproductive associations of serum polybrominated diphenyl ether and hydroxylated brominated diphenyl ether concentrations among women undergoing in vitro fertilization

DNA Hypermethylation of Brain-Derived Neurotrophic Factor is Associated with High Levels of Polybrominated Diphenyl Ethers in the Cord Serum: A Laizhou Wan Birth Cohort Study From China

Sulfonation and glucuronidation of hydroxylated bromodiphenyl ethers in human liver

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