Yu-Feng Li

Phthalate exposure and human semen quality: Results from an infertility clinic in China

Exposure to phthalates has been demonstrated to have adverse effects on male reproduction in animal studies, but findings in human studies have been inconsistent. We recruited 1040 men from the Reproductive Center of Tongji Hospital in Wuhan, China from March to June 2013. Each man provided one semen sample and two urine samples. Semen quality parameters and the urinary concentrations of eight phthalate metabolites were determined. After multivariable adjustments, the urinary concentrations of monobutyl phthalate (MBP) were found to be positively associated with the below-reference sperm concentration and total sperm count, and the odds ratios (ORs) comparing extreme MBP quartiles were 2.01 (95% CI: 1.07, 3.79; p for trend=0.06) and 1.80 (95% CI: 1.05, 3.08; p for trend=0.02), respectively. The associations were confirmed by multivariable linear regression analysis, which showed that the MBP concentration was significantly associated with decreasing trends in the sperm concentration and total sperm count (both p for trend <0.05). Additionally, we found significant dose-dependent relationships of the urinary level of mono-(2-ethylhexyl) phthalate (MEHP) and the percentage of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP (%MEHP) with an increased percentage of abnormal heads (both p for trend <0.01). Our findings suggest that environmental exposure to di-n-butyl phthalate (DBP) and DEHP may contribute to a decline in semen quality.

Phthalate exposure in association with serum hormone levels, sperm DNA damage and spermatozoa apoptosis: A cross-sectional study in China

Exposure to phthalates has been demonstrated to cause reproductive toxicity in animals, but evidence of the association between phthalates and markers of male reproductive function have been inconsistent in human studies. Here we examined whether environmental exposure to phthalates contributes to altered reproductive hormone levels, sperm DNA damage and spermatozoa apoptosis in a Chinese population. From March to June 2013, repeated urine samples collected from male partners of couples attending an infertility clinic in Wuhan, China were analyzed for 8 phthalate metabolites. Associations of the urinary phthalate metabolites with serum hormone levels (n=483), sperm DNA damage parameters (n=509) and spermatozoa apoptosis measures (n=467) were assessed using multivariable linear regression models. After adjusting for potential confounders, mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of di-(2-ethylhexyl)-phthalate (DEHP), was inversely associated with serum levels of estradiol, total testosterone (T) and free T (all P for trend<0.05). Additionally, we found positive dose-response relationships between the percentage of DEHP metabolites excreted as MEHP (%MEHP) and percentages of tail DNA (P for trend<0.05) and between three metabolites of DEHP [MEHP, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] and percentages of Annexin V+/PI- spermatozoa (all P for trend<0.05). Our findings strengthen the emerging evidence that exposure to DEHP may alter hormone levels, disrupt sperm DNA integrity and induce spermatozoa apoptosis.

Drinking-Water Disinfection By-products and Semen Quality: A Cross-Sectional Study in China

Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent. Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population. Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples. Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) μg/L (interquartile range, 6.01–10.96 μg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility. Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans. Citation: Zeng Q, Wang YX, Xie SH, Xu L, Chen YZ, Li M, Yue J, Li YF, Liu AL, Lu WQ. 2014. Drinking-water disinfection by-products and semen quality: a cross-sectional study in China. Environ Health Perspect 122:741–746; http://dx.doi.org/10.1289/ehp.1307067

Associations of urinary metal concentrations and circulating testosterone in Chinese men

Toxicological studies have shown that metals directly or indirectly influence testosterone (T) production, but the data from humans is limited and inconsistent. The aim of this study was to examine the associations between urinary metal concentrations and circulating T in Chinese men. Urinary concentrations of 13 metals (arsenic, cadmium, cobalt, chromium, copper, iron, lead, manganese, molybdenum, mercury, nickel, selenium and zinc) and serum levels of T were analyzed in 118 men from an infertility clinic. Multivariable linear regression was used to assess the effect of metals exposure on T. Among the measured metals, the median urinary Zn (359.36μg/g creatinine) and Co (0.16μg/g creatinine) concentrations were the highest and the lowest, respectively. Significant dose-response relationships were found between decreased T and urinary Mn and Zn, even when considering multiple metals (both P for trend <0.05). Our results indicate that elevated Mn and Zn are inversely associated with T production.

Baseline blood trihalomethanes, semen parameters and serum total testosterone: A cross-sectional study in China

Toxicological studies showed that trihalomethanes (THMs), the most abundant classes of disinfection by-products (DBPs) in drinking water, impaired male reproductive health, but epidemiological evidence is limited and inconsistent. This study aimed to examine the associations of baseline blood THMs with semen parameters and serum total testosterone in a Chinese population. We recruited 401 men seeking semen examination from the Reproductive Center of Tongji Hospital in Wuhan, China between April 2011 and May 2012. Baseline blood concentrations of THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were measured using SPME-GC/ECD method. Semen quality and serum total testosterone were analyzed. Multivariable linear regressions were used to assess the associations of baseline blood THM concentrations with semen parameters and serum total testosterone levels. We found that baseline blood THM concentrations were not associated with decrements in sperm motility, sperm straight-line and curvilinear velocity. However, moderate levels of BDCM (β=-0.13 million; 95% CI: -0.22, -0.03) and DBCM (β=-4.74%; 95% CI: -8.07, -1.42) were associated with decreased sperm count and declined sperm linearity compared with low levels, respectively. Suggestive dose-response relationships were also observed between elevated blood TCM or ∑ THMs (sum of TCM, BDCM, DBCM and TBM) concentration and decreased sperm concentration (both p for trend=0.07), and between elevated blood DBCM concentration and decreased serum total testosterone (p for trend=0.07). Our results indicate that elevated THM exposure may lead to decreased sperm concentration and serum total testosterone. However, the effects of THM exposure on male reproductive health still warrant further studies in humans.

Urinary trichloroacetic acid levels and semen quality: a hospital-based cross-sectional study in Wuhan, China.

Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured with the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20 million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1) μg/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence of the relationship between decreased sperm motility and increased urinary TCAA levels. The effect of exposure to DBPs on human male reproductive health in Chinese populations still warrants further investigations.

Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China☆

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend <0.05). These associations remained suggestive or significant after adjustment for multiple testing. There were no significant associations between semen phthalate metabolites and serum reproductive hormones. Our findings suggest that environmental exposure to phthalates may impair human semen quality.

Follicular fluid and urinary concentrations of phthalate metabolites among infertile women and associations with in vitro fertilization parameters

Evidence from toxicological studies has demonstrated that phthalates can lead to reduced fertility through effects on folliculogenesis, oocyte maturation and embryonic development, but human data are limited. Concentrations of eight phthalate metabolites in 110 follicular fluid (FF) and urine samples collected from 112 women attending an infertility clinic in Wuhan, China were quantified, and correlations between paired matrices were explored. Associations between metabolite concentrations and in vitro fertilization (IVF) parameters were evaluated with multivariable models. Six metabolites were detected in >72.73% of the FF samples. MEHP and MBP were the dominant metabolites with a median level of 2.80 and 2.05ng/mL, respectively. Significant correlations between the two matrices, urine and FF, were found for MEP (rs=0.44), and MBP (rs=0.22). FF and urinary metabolite concentrations were not associated with any IVF parameters. However, given the prevalence of phthalates exposure, further work is needed to elucidate the potential hazard on female reproduction.

Urinary Metal Concentrations in Relation to Semen Quality: A Cross-Sectional Study in China

Exposure to metals, including essential and nonessential elements, is widespread and may be associated with altered semen quality. This study aimed to examine the association between urinary metal concentrations and semen quality in a Chinese population. We measured semen quality parameters (sperm concentration, count, motility, normal morphology, and abnormal head) and 13 metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] in the urine of 394 men from an infertility clinic. Multivariable logistic and linear regressions were used to assess the relationship between the creatinine-adjusted urinary metal concentrations and semen quality parameters. We found a significant trend for decreased odds ratios (ORs) for below-reference sperm count with increasing Se quartiles (p for trend = 0.04) and a significant trend for increased sperm percent abnormal head with increasing Ni quartiles (p for trend = 0.03). These associations persisted, even when considering multiple metals. Our results suggest that Ni exposure may be associated with deteriorated sperm morphology and that Se exposure may be associated with better semen quality. However, our findings warrant further studies in a larger and general population.

Evaluation of exposure to trihalomethanes in tap water and semen quality: a prospective study in Wuhan, China.

Trihalomethanes (THMs) have been demonstrated to adversely affect male reproductive health in animals, but the evidence in humans is limited. The study aimed to examine the association between THM exposure and semen quality in a Chinese population. We recruited 324 men from the same water supply district in Wuhan, China between April 2011 and May 2012. Exposure to THMs was evaluated based on their concentrations in tap water measured within 90 days preceding semen collection, the uptake factors of THMs and personal information on ingestion and showering/bathing. We found that TTHM [sum of chloroform (TCM) and brominated THMs (Br-THMs)], TCM and Br-THM uptakes via ingestion were associated with significant or suggestive decreasing trends in sperm concentration (P for trend=0.01, 0.03 and 0.05, respectively) and sperm count (P for trend=0.02, 0.05 and 0.09, respectively). Our results suggest that THM exposure via ingestion may adversely affect semen quality.