Associations between repeated measurements of urinary polycyclic aromatic hydrocarbon metabolites and thyroid hormones among reproductive-aged men.

Polycyclic aromatic hydrocarbons (PAHs) have been shown to disrupt thyroid function in toxicological studies, but epidemiological evidence is inconsistent. Furthermore, little is known on potential effects of mixtures of PAHs. This study aimed to examine the associations of exposure to PAHs as individual chemicals and mixtures with thyroid hormones. We included 378 men from a Reproductive Medicine Center in Wuhan, China. Ten monohydroxylated PAH (OH-PAH) metabolites in repeated urine specimens collected at two-time points and three thyroid hormones [thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3)] in one serum sample were measured. Multivariable linear regression models were applied to assess the associations between individual OH-PAH metabolites and thyroid hormones, and the associations with mixtures of OH-PAH metabolites were assessed by Bayesian kernel machine regression (BKMR) models. Multivariable linear regression models showed inverse associations between urinary 1-OHNa and TSH, between urinary 1-OHPh and 9-OHPh and FT3, as well as between urinary 2-OHPh, 3-OHPh, 9-OHPh and ∑OHPh and FT4, regardless of these individual OH-PAH metabolites modeled as continuous or tertile variables (e.g., -21.57 % in TSH; 95 % CI: -35.33 %, -4.88 % for the third vs first tertiles of 1-OHNa; p for trend = 0.014). BKMR models showed negative overall effects of all urinary OH-PAH metabolite mixtures on TSH, FT3, and FT4, and 1-OHNa, 9-OHPh, and 2-OHPh as the most important contributors, respectively, with linear inverse exposure-response associations when holding other OH-PAH metabolites at their median concentrations. Urinary OH-PAH metabolites as individual chemicals and mixtures were adversely associated with thyroid hormones among reproductive-aged men.

Zhou B ，Deng Y ，Zeng Q ，Yang P ，Hu X ... -  《-》

Repeated measures of urinary polycyclic aromatic hydrocarbon metabolites in relation to altered reproductive hormones: A cross-sectional study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of ubiquitous environmental pollutants. In vivo and in vitro studies have demonstrated that PAHs can alter endocrine function, yet evidence from human studies is limited. The objective of this study was to investigate whether environmental exposure to PAHs was associated with altered reproductive hormone levels, using repeated measures of urinary OH-PAHs as biomarkers. We measured 10 monohydroxylated PAHs (OH-PAHs) in repeated urine samples from 371 men in an infertility clinic in Wuhan, China. Multivariable linear regression models were used to estimate the associations between average urinary OH-PAH levels and serum reproductive hormones, and restricted cubic spline models were further used to examine the shapes of dose-response relationships. We observed dose-response associations of urinary 2-hydroxynaphthalene (2-OHNa) with decreased serum free testosterone (fT) and urinary 1-hydroxypyrene (1-OHP), 9-hydroxyphenanthrene (9-OHPh), and 9-hydroxyfluorene (9-OHFlu) with decreased serum estradiol (all P for trends <0.05). These associations were linear and significant when these four OH-PAHs were modeled as continuous variables in restricted cubic spline models. Furthermore, a U-shaped association was observed across urinary 4-OHPh levels, with lower levels of serum sex hormone-binding globulin (SHBG) at median concentrations compared with 5th and 95th percentile concentrations. Environmental levels of PAH exposure in our study are associated with altered reproductive hormones. However, further research is needed to confirm our findings.

Yang P ，Sun H ，Gong YJ ，Wang YX ，Liu C ，Chen YJ ，Sun L ，Huang LL ，Ai SH ，Lu WQ ，Zeng Q ... -  《-》

Association between urinary polycyclic aromatic hydrocarbon metabolites and dyslipidemias in the Chinese general population: A cross-sectional study.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with metabolic diseases. However, relationships between PAH exposures and dyslipidemias have not been well addressed. To investigate associations between urinary PAH metabolite concentrations and dyslipidemias in the general population. Twelve urinary PAH metabolites and four serum lipid profiles were measured in 3640 Chinese adults from the Wuhan-Zhuhai cohort. Dyslipidemias, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were classified according to the levels of serum lipids. Multiple logistic regression models were used to estimate the associations between urinary PAH metabolites and the prevalence of dyslipidemias. The effects of PAH exposure routes on dyslipidemias were further estimated by stratified analysis. We found positive exposure-response relationships between urinary PAH metabolites and the prevalence of dyslipidemias. Compared with the lowest tertile of urinary PAH metabolites, increased risk of HyperTC were observed in those in the highest tertiles; The odds ratios (ORs) and 95% confidence intervals were 1.23 (1.03, 1.47), 1.44 (1.21, 1.71), 1.19 (1.01, 1.42), and 1.43 (1.20, 1.71) for 1-OHNa, 9-OHFlu, 1-OHPh, and 4-OHPh, respectively. Participants in the highest tertiles of 1-OHNa and 2-OHFlu had higher risk for HyperLDL-C, and the ORs were 1.21 (1.01, 1.45) and 1.18 (0.98, 1.42), respectively. Among smokers, only urinary 1-OHNa was associated with increased risk of HyperTC (1.36, 1.08-1.73) and HyperLDL-C (1.33, 1.01-1.74). While the increasing urinary levels of 9-OHFlu, 1-OHPh, and 4-OHPh were significantly associated with increased risk of HyperTC among non-smokers. In addition, the associations between urinary PAH metabolites and dyslipidemias were more pronounced among non-smokers who are cooked for themselves and had long-term traffic exposure. Elevated urinary PAH metabolites were associated with increased risks of HyperTC and HyperLDL-C. The source of PAH exposure could modify PAH species that affect dyslipidemias.

Ma J ，Zhou Y ，Liu Y ，Xiao L ，Cen X ，Li W ，Guo Y ，Kim M ，Yuan J ，Chen W ... -  《-》

Prenatal urinary polycyclic aromatic hydrocarbon metabolites, global DNA methylation in cord blood, and birth outcomes: A cohort study in China.

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play a key role in which PAHs exert its effects. Our study aimed to examine whether prenatal PAH exposure was associated with adverse birth outcomes and altered DNA methylation and to explore potential mediating roles of DNA methylation. Ten urinary PAH metabolites were measured from 106 pregnant women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing. Multivariable linear regression was used to estimate the associations of urinary PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis was also conducted. Prenatal urinary 2-hydroxynaphthalene (2-OHNa), ∑OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (∑OH-PAHs) were associated with lower birth length (e.g., -0.80%, 95% CI: -1.39%, -0.20% for the third vs. first tertile of 2-OHNa; p for trend = 0.01). Prenatal urinary 2-OHNa and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1 methylation (e.g., -1.88%, 95% CI: -3.73%, -0.10% for the third vs. first tertile tertile of 2-OHNa in Alu methylation; p for trend = 0.04). Mediation analysis failed to show a mediator effect of global DNA methylation in the association between prenatal urinary OH-PAHs and birth outcomes. Prenatal specific PAH exposures are associated with decreased birth length and global DNA methylation. However, global DNA methylation does not mediate the associations of prenatal PAH exposure with birth outcomes. Further studies are needed to confirm the results.

Yang P ，Gong YJ ，Cao WC ，Wang RX ，Wang YX ，Liu C ，Chen YJ ，Huang LL ，Ai SH ，Lu WQ ，Zeng Q ... -  《-》

Urinary concentrations of polycyclic aromatic hydrocarbon and phthalate metabolite mixtures in relation to semen quality among men attending an infertility clinic.

Previous studies have reported that exposure to phthalates and polycyclic aromatic hydrocarbons (PAHs) is individually associated with altered semen quality, but no human studies have evaluated their joint effects of exposure mixtures, a more real-world scenario. We aimed to explore urinary metabolite mixtures of phthalates and PAHs in associations with semen quality. Repeated spot-urine samples gathered from 695 men attending a fertility clinic were analyzed for urinary metabolites of eight phthalates and ten monohydroxylated-PAHs (OH-PAHs). Principal component analysis (PCA)-multivariable linear regression (MLR) model, quantile g-computation (qg-comp), and Bayesian kernel machine regression (BKMR) were applied to estimate the associations of urinary mixtures of phthalate and OH-PAH metabolites with semen quality. The overall effects of urinary mixtures of phthalate and PAH metabolites on semen quality were not statistically significant. However, hydroxynaphthalene (OHNa) factor identified from PCA was monotonically associated with decreased total sperm count and sperm concentration, whereas di(2-ethylhexyl) phthalate (DEHP) factor was non-monotonically related to increased progressive sperm motility and total sperm motility. Qg-comp and BKMR models confirmed these findings and identified 2-OHNa and 2-OHFlu as the primary negative contributors, whereas MEOHP and MEHP as the primary positive contributors. Our findings suggest that exposure to mixtures of naphthalene and DEHP is associated with altered semen quality. The finding is warranted to confirm in further well-designed epidemiological studies.

Deng YL ，Yang P ，Wang YX ，Liu C ，Luo Q ，Shi T ，Zeng JY ，Lu TT ，Chen PP ，Miao Y ，Zhang M ，Cui FP ，Lu WQ ，Zeng Q ... -  《-》