Niya Zhou

Semen quality of 1346 healthy men, results from the Chongqing area of southwest China

BACKGROUND Large studies on semen quality of the general healthy population from China are rare. METHODS A cross-sectional study was performed to evaluate the semen quality of 1346 healthy men residing in Chongqing area of southwest China in 2007. The semen parameters were measured and compared with the World Health Organization (WHO) criteria. A linear regression model was used to examine the determinants of semen quality. RESULTS The medians were 2.3 ml for semen volume, 77.8 x 10(6) per ml for semen concentration, 167.7 x 10(6) for total sperm count, 33% for sperm rapid progressive motility, 52.6% for sperm progressive motility and 70.9% for total motility. According to WHO criteria, 61.1% of healthy males had at least one semen parameter below normal threshold values. Season and abstinence duration were found to be significantly associated with semen quality (P < 0.001). Age, smoking, alcohol use and BMI had little or no effect on semen parameters. CONCLUSIONS A high proportion of healthy males in Chongqing area of southwest China had abnormal semen parameters values according to WHO criteria. The semen parameters in the study population were markedly different from those reported for the other Chinese, USA and European populations. The differences remain unexplained and may be due to demographic characteristics, lifestyle, environmental factors or genetic variation.

Association between urinary polycyclic aromatic hydrocarbon metabolites and sperm DNA damage: a population study in Chongqing, China.

Background Polycyclic aromatic hydrocarbons (PAHs), a class of the most ubiquitous environmental contaminants, may reduce male reproductive functions, but the data from human population studies are very limited. Objectives We designed this study to determine whether environmental exposure to PAHs contributes to the alteration in semen quality, sperm DNA damage, and apoptosis in the general male human population. Methods We measured urinary levels of four PAH metabolites and assessed semen quality, sperm apoptotic markers with Annexin V assay, and sperm DNA damage with comet assay in 232 men from Chongqing, China. Results We found that increased urinary 2-hydroxynaphthalene (2-OHNa) levels were associated with increased comet parameters, including the percentage of DNA in the tail (tail%) [β coefficient = 13.26% per log unit 2-OHNa (micrograms per gram creatinine); 95% confidence interval (CI), 7.97–18.55]; tail length (12.25; 95% CI, 0.01–24.52), and tail distribution (7.55; 95% CI, 1.28–18.83). The urinary level of 1-hydroxypyrene was associated only with increased tail% (5.32; 95% CI, 0.47–10.17). Additionally, the increased levels of four urinary PAH metabolites were significantly associated with decreased vital Annexin V negative sperm counts. However, there was no significant association between urinary PAH metabolite levels and human semen parameters or morphology of the sperm samples. Conclusions Our data indicate that the environmental level of PAH exposure is associated with increased sperm DNA damage but not with semen quality. These findings suggest that exposure to PAHs may disrupt sperm DNA and thereby interfere with human male fertility.

Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China.

This study was designed to investigate the phthalates exposure levels in general population in Chongqing City of China, and to determine the possible associations between phthalate exposure and male reproductive function parameters. We recruited 232 general men through Chongqing Family Planning Research Institute and Reproductive Center of Chongqing. In a single spot urine sample from each man, phthalate metabolites, including mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-benzyl phthalate (MBzP), phthalic acid (PA), and total PA were analyzed using solid phase extraction and coupled with high-performance liquid chromatography and detection by tandem mass spectrometry. Semen parameters were dichotomized based on World Health Organization reference values. Sperm DNA damage were analyzed using the alkaline single-cell gel electrophoresis assay. Reproductive hormones were determined in serum by the radioimmunoassay kit. We observed a weak association between urinary MBP concentration and sperm concentration in Chongqing general population. MBP levels above the median were 1.97 times (95% confidence interval [CI] 0.97-4.04) more likely to have sperm concentration below the reference value. There were no other associations between phthalate metabolites and reproductive function parameters after adjusted for potential risk factors. Our study suggested that general population in Chongqing area of China exposure to the environmental level of phthalate have weak or without adverse effects on the reproduction.

Lifestyles Associated With Human Semen Quality: Results From MARHCS Cohort Study in Chongqing, China.

AbstractDecline of semen quality in past decades is suggested to be potentially associated with environmental and sociopsychobehavioral factors, but data from population-based cohort studies is limited.The male reproductive health in Chongqing College students (MARHCS) study was established in June 2013 as a perspective cohort study that recruited voluntary male healthy college students from 3 universities in Chongqing. The primary objectives of the MARHCS study are to investigate the associations of male reproductive health in young adults with sociopsychobehavioral factors, as well as changes of environmental exposure due to the relocation from rural campus (in University Town) to metro-campus (in central downtown). A 93-item questionnaire was used to collect sociopsychobehavioral information in manner of interviewer–interviewing, and blood, urine and semen samples were collected at the same time.The study was initiated with 796 healthy young men screened from 872 participants, with a median age of 20. About 81.8% of this population met the WHO 2010 criteria on semen quality given to the 6 routine parameters. Decreases of 12.7%, 19.8%, and 17.0%, and decreases of 7.7%, 17.6%, and 14.7% in total sperm count and sperm concentration, respectively, were found to be associated with the tertiles of accumulated smoking amount. Fried food consumption (1–2 times/wk or ≥3 times/wk vs nonconsumers) was found to be associated with decreased total sperm count (10.2% or 24.5%) and sperm concentration (13.7% or 17.2%), respectively. Coffee consumption was found to be associated with increased progressive and nonprogressive motility of 8.9% or 15.4% for subjects consuming 1–2 cups/wk or ≥3 cups/wk of coffee, respectively. Cola consumption appeared an association with decreased semen volume at 4.1% or 12.5% for 1–2 bottles/wk or ≥3 bottles/wk.A cohort to investigate the effects of environmental/sociopsychobehavioral factors act on semen quality was successfully set up. We found smoking, coffee/cola/fried foods consumption to be significantly associated with semen quality from the baseline investigation.

Inverse U-shaped Association between Sleep Duration and Semen Quality: Longitudinal Observational Study (MARHCS) in Chongqing, China

STUDY OBJECTIVES To investigate the association between sleep duration and semen parameters as well as reproductive hormone levels. METHODS We designed a cohort of male college students in Chongqing, China. A total of 796 subjects were recruited in 2013 and 656 (82.4%) were followed up in 2014. Each time, semen and peripheral blood samples were collected for semen quality and reproductive hormone measurement. Sleep duration was estimated by revised Munich Chronotype Questionnaire. In 2014, sleep quality was also measured by Pittsburgh Sleep Quality Index (PSQI). RESULTS There was a substantial inverse U-shaped association between sleep duration and two semen parameters (semen volume and total sperm number), with 7.0-7.5 h/day of sleep showing highest parameters. Either longer or shorter sleep was associated with decreased semen parameters in a dose-response manner (P = 0.002 and 0.001, respectively). Sleeping > 9.0 h was associated with a 21.5% (95% confidence interval 9.2, 32.2) reduction in semen volume and 39.4% (23.3, 52.1) reduction in total sperm number; sleeping ≤ 6.5 h was associated with 4.6% (-10.5, 22.3) and 25.7% (-1.2, 60.1) reduction. Increase of the two parameters was found in those who changed sleep duration toward 7.0-7.5 h/day from 2013 to 2014. The U-shaped association was independent from PSQI and was replicated in another dataset of 1,346 males. No association found between sleep duration and reproductive hormone. CONCLUSIONS Either restricted or excessive sleep may impair semen quality. Further research is needed to validate this finding.

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.

Anogenital distance is associated with serum reproductive hormones, but not with semen quality in young men

STUDY QUESTION Is anogenital distance associated with semen parameters and serum reproductive hormone levels in males? SUMMARY ANSWER Anogenital distance is associated with serum reproductive hormones, but not with semen quality. WHAT IS KNOWN ALREADY Epidemiological studies have suggested that anogenital distance (AGD) may be associated with testicular dysfunction in adult men. However, the role of AGD in estimating male reproductive function remains unclear. STUDY DESIGN, SIZE, DURATION We examined the associations between AGD and semen parameters and reproductive hormones levels in 656 young college students in a Male Reproductive Health in Chongqing College Students (MARHCSs) cohort study in June of 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS In this study, two variants of AGD (AGDAP and AGDAS) were measured in 656 university students. Serum levels of testosterone (T), estradiol (E2), progesterone (P), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG) and inhibin-B; and semen quality outcomes, including semen volume, sperm concentration, total sperm number, sperm progressive motility, total motility and morphology, were assessed. The associations between AGD and semen parameters/reproductive hormones levels were analyzed using multiple regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE Both AGDAS and AGDAP were not associated with any semen parameters. In the non-parametric correlation analysis, AGDAP were correlated with sperm progressive motility and reproductive hormones of E2, testosterone, SHBG and the testosterone/LH ratio. However, body mass index (BMI) also significantly correlated with serum testosterone ( ITALIC! r = -0.216, ITALIC! P = <0.0001) and SHBG ( ITALIC! r = -0.229, ITALIC! P = <0.001). In the multiple regression models, AGDAP was negatively associated with the serum E2 level (95% CI, -0.198 to -0.043; ITALIC! P = 0.002) and positively associated with the ratio of T/E2 (95% CI, 0.004-0.011; ITALIC! P = 0.001) after an adjustment for BMI and other confounders. LIMITATIONS, REASONS FOR CAUTION Using only a single semen sample to predict male reproductive function over a longer period is a potential limitation of the present study. The other limitation is the cross-sectional nature of the study design. Longitudinal data from an extended follow-up on a large cohort would be more definitive. WIDER IMPLICATIONS OF THE FINDINGS Our results do not support previous studies where AGD is associated with male semen quality. The utility of AGD in predicting reproductive outcomes in adult males should thus be considered prudently. STUDY FUNDING/COMPETING INTERESTS This study was supported by the Key Program of Natural Science Funding of China (no. 81130051), Young Scientist Program of NSFC (no. 81502788) and the National Scientific and Technological Support Program of China (no. 2013BAI12B02). None of authors had any competing interests to declare.

Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population

BACKGROUND Environment-Protection-Agency Reference Doses (EPA RfDs) for phthalate intakes are based on limited evidence, especially regarding low-dose male-reproductive toxicity. This study investigates the association between phthalate exposure and semen parameters and reproductive hormones in a general population with low phthalate exposure compared to the EPA RfDs. METHODS The MARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited 796 male students, who experienced a relocation of campuses and shifting environmental exposure. Urine, semen and blood before and after the relocation was collected and investigated for: (1) the associations between 13 urinary phthalate metabolites and 11 semen/hormone outcomes (five semen parameters including semen volume, sperm concentration, total sperm number, progressive motility, normal morphology) and six serum reproductive hormones including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, testosterone; (2) re-analysis of the metabolite-outcome associations in the subjects with estimated phthalate intakes below the RfDs; (3) a change in phthalate metabolites and change in semen/hormone outcomes after the relocation; (4) the association between these changes. RESULTS (1) All but two semen/hormone outcomes were associated with at least one phthalate metabolite, e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6% decrease of sperm concentration, total sperm number and progressive motility respectively. (2) In the subjects with phthalate intakes below the RfDs, these metabolite-outcome associations remained significant. (3) All metabolites except mono(2-ethylhexyl) phthalate declined after relocation (P<0.001 respectively); at the same time, semen volume, normal morphology, estradiol and luteinizing hormone increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%). (4) The changes in semen volume, normal morphology, estradiol and testosterone, but not the change in luteinizing hormone after relocation, were associated with the changes in the phthalate metabolites. CONCLUSIONS Phthalate exposure is associated with interrupted semen quality and reproductive hormones in the human population even with a dose given below the RfDs. These effects, however, may only partially revert back when exposure decreases, thus emphasizing the urgency of stricter phthalate administration.

Effects of cell phone use on semen parameters: Results from the MARHCS cohort study in Chongqing, China.

Epidemiological and experimental evidence for detrimental effects of cell phone use on semen quality is still equivocal. And that recruiting participants from infertility clinic not from general population may raise the possibility of a selection bias. To investigate effects of cell phone use on semen parameters in a general population,We screened and documented the cell phone use information of 794 young men from the Male Reproductive Health in Chongqing College students (MARHCS) cohort study in 2013, followed by 666 and 568 in 2014 and 2015, respectively. In the univariate regression analyses, we found that the daily duration of talking on the cell phone was significantly associated with decreased semen parameters, including sperm concentration [β coefficient=-6.32% per unit daily duration of talking on the cell phone (h); 95% confidence interval (CI), -11.94, -0.34] and total sperm count (-8.23; 95% CI, -14.38, -1.63) in 2013; semen volume (-8.37; 95% CI, -15.93, -0.13) and total sperm count (-16.59; 95% CI, -29.91, -0.73) in 2015]. Internet use via cellular networks was also associated with decreased sperm concentration and total sperm counts in 2013 and decreased semen volume in 2015. Multivariate analyses were used to adjust for the effects of potential confounders, and significant negative associations between internet use and semen parameters remained. Consistent but nonsignificant negative associations between talking on the cell phone and semen parameters persisted throughout the three study years, and the negative association was statistically significant in a mixed model that considered all three years of data on talking on the cell phone and semen quality. Our results showed that certain aspects of cell phone use may negatively affect sperm quality in men by decreasing the semen volume, sperm concentration, or sperm count, thus impairing male fertility.

Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene-exposed workers in a matched study in China

1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78‰ versus 5.62 ± 2.41‰) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79‰ versus 1.13 ± 1.34‰) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.