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 ... -  《-》

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 ... -  《-》

Polycyclic aromatic hydrocarbons exposure decreased sperm mitochondrial DNA copy number: A cross-sectional study (MARHCS) in Chongqing, China.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants that have adverse effects on the male reproductive function. Many studies have confirmed that PAHs preferentially accumulate in mitochondria DNA relative to nuclear DNA and disrupt mitochondrial functions. However, it is rare whether exposure to PAHs is associated with mitochondrial damage and dysfunction in sperm. To evaluate the effects of PAHs on sperm mitochondria, we measured mitochondrial membrane potential (MMP), mitochondrial DNA copy number (mtDNAcn) and mtDNA integrity in 666 individuals from the Male Reproductive Health in Chongqing College Students (MARHCS) study. PAHs exposure was estimated by measuring eight urinary PAH metabolites (1-OHNap, 2-OHNap, 1-OHPhe, 2-OHPhe, 3-OHPhe, 4-OHPhe, 2-OHFlu and 1-OHPyr). The subjects were divided into low, median and high exposure groups using the tertile levels of urinary PAH metabolites. In univariate analyses, the results showed that increased levels of 2-OHPhe, 3-OHPhe, ∑Phe metabolites and 2-OHFlu were found to be associated with decreased sperm mtDNAcn. After adjusting for potential confounders, significantly negative associations of these metabolites remained (p = 0.039, 0.012, 0.01, 0.035, respectively). Each 1 μg/g creatinine increase in 2-OHPhe, 3-OHPhe, ∑Phe metabolites and 2-OHFlu was associated with a decrease in sperm mtDNAcn of 9.427%, 11.488%, 9.635% and 11.692%, respectively. There were no significant associations between urinary PAH metabolites and sperm MMP or mtDNA integrity. The results indicated that the low exposure levels of PAHs can cause abnormities in sperm mitochondria.

Ling X ，Zhang G ，Sun L ，Wang Z ，Zou P ，Gao J ，Peng K ，Chen Q ，Yang H ，Zhou N ，Cui Z ，Zhou Z ，Liu J ，Cao J ，Ao L ... -  《-》

Urinary Polycyclic Aromatic Hydrocarbon Metabolites and Human Semen Quality in China.

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

Shorter sperm telomere length in association with exposure to polycyclic aromatic hydrocarbons: Results from the MARHCS cohort study in Chongqing, China and in vivo animal experiments.

It has been well demonstrated that polycyclic aromatic hydrocarbons (PAHs) can cause reproductive toxicity, and shorter telomere length in sperm may be one of the factors causing male infertility. However, whether exposure to PAHs is associated with sperm telomere length (STL) has never been evaluated. The present study aimed to assess the potential association between PAHs exposure and STL, and to explore potential biomarkers that may predict the effects of low-level exposure to PAHs on human sperm. Questionnaires and biological samples were collected from 666 volunteers participating in the Male Reproductive Health in Chongqing College Students (MARHCS) cohort study in 2014. Semen parameters were measured for 656 participants, while urinary PAH metabolites, STL and sperm apoptosis were successfully measured for 492, 444 and 628 participants, respectively. The linear regression analysis revealed that increased levels of urinary 1-hydroxypyrene (1-OHPyr) and 1-hydroxynapthalene (1-OHNap) were associated with decreased STL (-0.385; 95% CI, -0.749, -0.021 for 1-OHPyr; and -0.079; 95% CI, -0.146, -0.011 for 1-OHNap). The significant negative associations remained after adjusting for potential confounders. However, no significant associations were observed between urinary PAH metabolites and semen quality or sperm apoptosis. We also administrated rats with benzo[a]pyrene (B[a]P; 0, 1, 5, and 10mg/kg) for 4weeks and found shorter STL and decreased telomerase expression in germ cells in a dose-dependent manner. In conclusion, environmental exposure to some PAHs may be associated with decreased human STL, and the in vivo animal results also demonstrate the adverse effects of B[a]P on telomere of male germ cells.

Ling X ，Zhang G ，Chen Q ，Yang H ，Sun L ，Zhou N ，Wang Z ，Zou P ，Wang X ，Cui Z ，Liu J ，Ao L ，Cao J ... -  《-》