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 ... -  《-》

Effects of environmental and lifestyle exposures on urinary levels of polycyclic aromatic hydrocarbon metabolites: A cross-sectional study of urban adults in China.

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.

Cao L ，Wang D ，Wen Y ，He H ，Chen A ，Hu D ，Tan A ，Shi T ，Zhu K ，Ma J ，Zhou Y ，Chen W ... -  《-》

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 ... -  《-》

Urinary metabolites of polycyclic aromatic hydrocarbons, sperm DNA damage and spermatozoa apoptosis.

Inconsistent results between polycyclic aromatic hydrocarbons (PAHs) exposure and adverse male reproductive health have been reported in humans. To assess whether PAH exposure is associated with declined sperm function. Ten monohydroxylated PAHs (OH-PAHs) metabolites were analyzed in repeated urine samples from an infertility clinic. We used multivariable linear models to estimate the associations of urinary OH-PAH metabolites with sperm DNA damage (n=405) and spermatozoa apoptosis (n=366). The shapes of dose-dependent associations of exposure measurements with outcomes were further evaluated by restricted cubic splines. Multiple comparisons were adjusted by false discovery rate (FDR). We found that urinary 9-hydroxyfluorene (9-OHFlu) was associated with increased tail length and comet length (p for trend=0.05 and 0.01, respectively), and that urinary 9-hydroxyphenanthrene (9-OHPh) was associated with decreased percentage of Annexin V-/PI- spermatozoa (p for trend=0.04). Also, suggestive associations of urinary 9-OHPh and ∑OHFlu with increased comet length, and urinary 9-OHFlu and 2-OHPh with decreased percentage of Annexin V-/PI- spermatozoa were observed (all p for trends <0.10). Further, these dose-dependent associations were confirmed in restricted cubic splines. Our results suggest that environmental exposure to fluorene and phenanthrene are associated with declined sperm function.

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

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

Cao S ，Wan Y ，Li Y ，Xu S ，Xia W ... -  《-》