Blood trihalomethane concentrations in relation to sperm mitochondrial DNA copy number and telomere length among 958 healthy men.

BACKGROUND: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. OBJECTIVE: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. METHODS: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility. RESULTS: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. CONCLUSION: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction.

Associations of Urinary Trichloroacetic Acid Concentrations with Spermatozoa Apoptosis and DNA Damage in a Chinese Population.

Exposure to trichloroacetic acid (TCAA) has been associated with impaired semen quality; however, its association with spermatozoa apoptosis and DNA damage remains unclear. We, therefore, collected single semen and repeated urine samples from male partners of couples attending a reproductive center, which were measured for spermatozoa apoptosis and DNA damage parameters and TCAA concentrations, respectively. Multivariable linear regression models were used to explore the associations between urinary TCAA concentrations and spermatozoa apoptosis (n = 462) and DNA damage parameters (n = 512). After adjusting for potential confounders, positive dose-response relationships were found between urinary TCAA concentrations and percentage of tail DNA (tail%) and tail-distributed moment (TDM) (both p for trend <0.10). Compared with men in the lowest tertile of urinary TCAA concentrations, men in the highest tertile had a greater tail% and TDM of 6.2% (95% CI: 0.7, 12.2%) and 8.9% (95% CI: -1.9, 20.5%), respectively. Urinary TCAA concentrations were unrelated to spermatozoa apoptosis parameters in a dose-response manner. However, urinary TCAA concentrations were positively associated with the percentage of Annexin V+/PI- spermatozoa (apoptotic cells), when urinary TCAA concentrations were modeled as continuous variables. Our results suggest that exposure to TCAA at concentrations in real-world scenarios may be associated with spermatozoa apoptosis and DNA damage.

Exposure to disinfection by-products and reproductive hormones among women: Results from the Tongji Reproductive and Environmental (TREE) study.

BACKGROUND: Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. OBJECTIVE: To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. METHODS: We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (E2), total testosterone (T), progesterone (PRGE), and prolactin (PRL) were determined. Multivariate linear regression models were performed to assess the associations of urinary DCAA and TCAA concentrations with reproductive hormone levels. Dose-response relationships were investigated using natural cubic spline (NCS) and restricted cubic spline (RCS) models. RESULTS: After adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 µg/L and 6.30 µg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones. CONCLUSION: Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort.

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters (p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

Urinary biomarker of strontium exposure is positively associated with semen quality among men from an infertility clinic.

Experimental studies have shown that nonradioactive strontium (Sr), in the form of Sr2+, have a positive effect on semen quality, but human evidence is lacking. This study aimed to examine the associations between nonradioactive Sr exposure and semen quality in Chinese men (n = 394). We recruited men who presented at an infertility clinic in Wuhan, China to seek for semen parameter analyses. Urinary Sr concentration as an exposure biomarker was measured using inductively coupled plasma mass spectrometer. We estimated the associations between urinary Sr concentrations and semen parameters using multivariable logistic and linear regression models. In multivariable linear regressions models, positive dose-response associations were estimated for sperm concentration, motility, and count across increasing urinary Sr quartiles (all p for trends<0.05), and the consistent positive associations were also observed for urinary Sr concentration modeled as a continuous exposure. In multivariable logistic models, decreased risks of below-reference sperm concentration, motility, and count were also estimated across increasing urinary Sr quartiles (all p for trends<0.05). Our results suggest that nonradioactive Sr exposure may have a beneficial effect on semen quality, but more investigations are warranted to confirm the results.

Urinary Biomarker of Prenatal Exposure to Disinfection Byproducts, Maternal Genetic Polymorphisms in CYP2E1 and GSTZ1, and Birth Outcomes.

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China.

BACKGROUND: Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. OBJECTIVE: To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. METHODS: We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. RESULTS: We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: -0.35, -0.07; P for trend = 0.003), 0.46 cm (95% CI: -0.81, -0.10; P for trend = 0.01) and 0.17 cm (95% CI: -0.30, -0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. CONCLUSION: The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Profiles, variability and predictors of concentrations of blood trihalomethanes and urinary haloacetic acids along pregnancy among 1760 Chinese women.

Blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) are the leading candidate biomarkers for disinfection byproduct (DBP) exposure. However, no studies have assessed the exposure profiles, temporal variability, and potential predictors of these biomarkers during pregnancy. Here we collected blood (n = 4304) and urine samples (n = 4165) from 1760 Chinese pregnant women during early, mid-, and late pregnancy, which were separately analyzed for 4 THMs and 2 HAAs. We calculated the intraclass correlation coefficients (ICCs) to assess the variability of these biomarkers and estimated their correlations with sociodemographic, water-use behavioral, dietary and sample collection factors using mixed models. The median concentrations of TCM, BDCM, Br-THMs [sum of BDCM, dibromochloromethane (DBCM), bromoform (TBM)], total THMs (TTHMs, sum of TCM and Br-THMs), DCAA and TCAA in the water distribution system were 4.2 µg/L, 1.7 µg/L, 2.9 µg/L, 7.1 µg/L, 3.4 µg/L and 8.2 µg/L, respectively. Chloroform (TCM), bromodichloromethane (BDCM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected in > 75% of the biospecimens. Repeated measurements of blood TCM, BDCM, Br-THMs and TTHMs and urinary DCAA and TCAA uniformly exhibited high variability (ICCs = 0.01-0.13); the use of a single measurement to classify gestational average exposure resulted in a high degree of exposure misclassification. The sampling season was a strong predictor of all analyzed DBPs. Additionally, we detected a positive association of blood TCM and BDCM with household income, urinary DCAA with age, and urinary TCAA with tap water usage, education level and amount of tap water consumed. Inverse associations were found between blood BDCM and vegetable consumption, and between blood Br-THM and TTHM and time interval since the last bathing/showering. Afternoon samples had lower DCAA concentrations than did early morning samples. Our results indicate that blood THM and urinary HAA concentrations vary greatly over the course of pregnancy and are affected by sampling season, time of day of blood/urine collection, sociodemographic factors, recent water-use activities and dietary intake.

Mediation of the relationship between phthalate exposure and semen quality by oxidative stress among 1034 reproductive-aged Chinese men.

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

Predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men.

BACKGROUND: Certain phthalates are suspected to be endocrine disruptors that are adversely associated with male reproductive health. However, the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men have not been thoroughly studied. OBJECTIVE: To investigate the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among adult Chinese males. METHOD: We measured mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-octyl phthalate (MOP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations in seminal plasma and repeated spot-urine samples from 687 men who visited a reproductive center. Mixed-effect models were used to examine the associations of sociodemographic, lifestyle and medical factors with urinary metabolite concentrations. Linear regression models were used to identify predictors of metabolite concentrations in seminal plasma and correlations between metabolite concentrations in spot urine samples and seminal plasma. RESULTS: Measurements taken from spot urine samples poorly predicted same-day seminal plasma concentrations (all R2<0.10). Inverse associations were observed between education level and urinary MBP and MEOHP and between household income and urinary MMP; receiving intravenous infusion therapy was associated with increased urinary MBP, MEHHP and MEOHP, use of facial cleanser/cream was associated with increased MEP, and smoking was associated with increased MEHP. The predictors of metabolite concentrations in seminal plasma differed from those in urine, except for the association of intravenous infusion therapy with MBP. BMI was associated with increased seminal plasma MBP, MEHP and MEOHP, smoking was associated with increased MEP, and contact with plastics was associated with increased MEOHP. CONCLUSIONS: Phthalate metabolite concentrations in adult men varied in accordance with sociodemographic variables, lifestyle factors and intravenous therapy. Measures of metabolite levels in urine may not directly reflect the exposure status of the male reproductive system.

Investigating the performance of three modified activated sludge processes treating municipal wastewater in organic pollutants removal and toxicity reduction.

This study investigated the treatment performance of three types of modified activated sludge processes, i.e., anoxic/oxic (A/O), anaerobic/anoxic/oxic (A2/O) and oxidation ditch process, in treating municipal wastewater by measuring physicochemical and spectroscopic parameters, and the toxicity of the influents and effluents collected from 8 full-scale municipal wastewater treatment plants (MWTPs). The relationships between spectroscopic and physicochemical parameters of the wastewater samples and the applicability of the nematode Caenorhabditis elegans (C. elegans) bioassays for the assessment of the toxic properties of municipal wastewater were also evaluated. The results indicated that the investigated MWTPs employing any of A/O, A2/O and oxidation ditch processes could effectively control the discharge of major wastewater pollutants including biochemical oxygen demand (BOD), chemical oxygen demand, nitrogen and phosphorus. The oxidation ditch process appeared to have the advantage of removing tyrosine-like substances and presented slightly better removal efficiency of tryptophan-like fluorescent (peak T) substances than the A/O and A2/O processes. Both ultraviolet absorbance at 254nm and peak T may be used to characterize the organic load of municipal wastewater, and peak T can be adopted as a gauge of the BOD removal efficacy of municipal wastewater treatment. Using C. elegans-based oxygen consumption rate assay for monitoring municipal wastewater toxicity deserves further investigations.

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

Toxicological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs) exposure impairs male reproductive health. However, the epidemiological evidence is limited and discordant. Our goal was to investigate the relationship between PAH exposures and human semen quality. We analyzed 12 urinary metabolites of PAHs from 933 men who sought semen quality analysis in an infertility clinic in Wuhan, China. Associations with semen quality were assessed using a multivariable linear regression. Restricted cubic splines were used to explore the dose-response relationships between urinary metabolites of PAHs and semen quality. We observed inverse associations between urinary 1-hydroxynaphthalene (1-OHNa) and sperm count, sperm concentration, and percentage of normal morphology (all p for trends <0.05) as well as between urinary ∑OHNa (sum of 1-OHNa and 2-OHNa) and sperm concentration (p for trend =0.04). Additionally, we found inverse associations between urinary 9-hydroxyphenanthrene (9-OHPh) and semen volume and sperm straight-line velocity (both p for trends <0.05) as well as between urinary ∑OHPh (sum of 1-, 2-, 3-, 4-, and 9-OHPh) and sperm count (p for trend =0.04). These dose-response relationships were further confirmed in the curves of the restricted cubic splines. Our data suggest that exposure to naphthalene and phenanthrene is related to decreased semen quality. Our results contribute to the growing body of evidence regarding the widespread exposure to PAHs and the detriment to male reproductive function.

Comparative cytotoxic and genotoxic potential of 13 drinking water disinfection by-products using a microplate-based cytotoxicity assay and a developed SOS/umu assay.

The implications of disinfection by-products (DBPs) present in drinking water are of public health concern because of their potential mutagenic, carcinogenic and other toxic effects on humans. In this study, we selected 13 main DBPs found in drinking water to quantitatively analyse their cytotoxicity and genotoxicity using a microplate-based cytotoxicity assay and a developed SOS/umu assay in Salmonella typhimurium TA1535/pSK1002. With the developed SOS/umu test, eight DBPs: 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-fura3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]-furanone (MX), dibromoacetonitrile (DBN), iodoacetic acid (IA), bromochloroacetonitrile (BCN), bromoacetic acid (BA), trichloroacetonitrile (TCN), dibromoacetic acid (DBA) and dichloroacetic acid (DCA) were significantly genotoxic to S. typhimurium. Three DBPs: chloroacetic acid (CA), trichloroacetic acid (TCA) and dichloroacetonitrile (DCN) were weakly genotoxic, whereas the remaining DBPs: chloroacetonitrile (CN) and chloral hydrate (CH) were negative. The rank order in decreasing genotoxicity was as follows: MX > DBN > IA > BCN > BA > TCN > DBA > DCA > CA, TCA, DCN > CN, CH. MX was approximately 370 000 times more genotoxic than DCA. In the microplate-based cytotoxicity assay, cytotoxic potencies of the 13 DBPs were compared and ranked in decreasing order as follows: MX > IA > DBN > BCN > BA > TCN > DCN > CA > DCA > DBA > CN > TCA > CH. MX was approximately 19 200 times more cytotoxic than CH. A statistically significant correlation was found between cytotoxicity and genotoxicity of the 13 DBPs in S. typhimurium. Results suggest that microplate-based cytotoxicity assay and the developed SOS/umu assay are feasible tools for analysing the cytotoxicity and genotoxicity of DBPs, particularly for comparing their toxic intensities quantitatively.

Predictors of Third Trimester Blood Trihalomethanes and Urinary Trichloroacetic Acid Concentrations among Pregnant Women.

Prenatal exposure to disinfection byproducts (DBPs) has been associated with a variety of adverse birth outcomes. However, little is known about predictors of prenatal biomarkers of exposure to DBPs among pregnant women. We aimed to identify predictors of third trimester blood trihalomethanes (THMs) and urinary trichloroacetic acid (TCAA) concentrations, two biomarkers of exposure to DBPs, among pregnant women. Blood samples, urine samples, and questionnaires on individual characteristics and water-use activities were collected from 893 pregnant women in a Chinese cohort study. Maternal blood THM [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA concentrations were measured. We used multivariable linear regression to identify the predictors of third trimester blood THM and creatinine-adjusted urinary TCAA concentrations. The geometric mean of blood TTHM (sum of TCM, BDCM, DBCM, and TBM) and creatinine-adjusted urinary TCAA concentrations were 51.90 ng/L and 9.66 µg/g creatinine, respectively. Study city was the strongest significant predictors of blood THM and creatinine-adjusted urinary TCAA concentrations. Prenatal body mass index (BMI) was associated with decreased blood THM and decreased creatinine-adjusted urinary TCAA concentrations. Age was associated with increased blood Br-THM (sum of BDCM, DBCM, and TBM) concentrations. Intake of boiled water and passive smoking were associated with lower blood THM concentrations. The predictors of blood THM and urinary TCAA concentrations identified in this study provide potential health implications on how to reduce DBP exposure during pregnancy.

Interactions between CYP2E1, GSTZ1 and GSTT1 polymorphisms and exposure to drinking water trihalomethanes and their association with semen quality.

Trihalomethanes (THMs) have been reported to be associated with altered semen quality, and this association may be modified by inherited differences in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTZ1 and GSTT1), which metabolize THMs. We conducted a cross-sectional study to examine the interactions between CYP2E1, GSTZ1 and GSTT1 polymorphisms and exposure to THMs on semen quality among 401 men from the Reproductive Center of Tongji Hospital in Wuhan China. The baseline blood concentrations of four individual THMs, chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM), were measured as biomarkers of exposure to drinking water THMs. Genotypes were determined by real-time PCR, and semen-quality parameters were evaluated according to the World Health Organization guidelines. GSTT1 genotype significantly modified the association between exposure to Br-THMs (sum of BDCM, DBCM and TBM) and below-reference sperm motility (Pint=0.02). Men with above-median blood Br-THM levels had an increased odds ratio (OR) of below-reference sperm compared to men with below-median blood Br-THM levels (OR=2.15, 95% CI: 1.11, 4.19) in the GSTT1 null genotype only. In addition, we found that men with a TT of CYP2E1 rs 915,906 had higher blood TCM and TTHM (sum of TCM, BDCM, DBCM and TBM) concentrations than men with a CT/CC of CYP2E1 rs 915,906. Our results suggest that GSTT1 polymorphisms modify Br-THM exposure relation with semen quality, and CYP2E1 polymorphisms are associated with internal levels of exposure to THMs.

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.

Semen phthalate metabolites, spermatozoa apoptosis, and DNA damage: a cross-sectional study in China.

Toxicological studies have shown that phthalates, a class of widely used chemicals, can impair male reproductive function, but epidemiological evidence is inconsistent. This study aimed to investigate the associations of semen phthalate metabolites with sperm apoptosis and DNA damage in a Chinese population. We assessed sperm apoptosis markers with Annexin V/PI analysis and sperm DNA integrity with comet assay before measuring eight phthalate metabolites in semen by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) among 463 men from Wuhan, China. We found a suggestive dose-response relationship between semen mono-(2-ethylhexyl) phthalate (MEHP) and an increased percentage of Annexin V+/PI- sperm (p for trend of <0.10). We also observed that semen monomethyl phthalate (MMP) and monoethyl phthalate (MEP) were associated with significant dose-related increases in tail length of the comet (both p for trend of <0.01). In conclusion, our data indicate that semen MEHP is associated with increased sperm apoptosis and that semen MMP and MEP are associated with increased sperm DNA damage in a Chinese population.

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.

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.

Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men.

Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficients (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08-0.37) and TCAA (ICC=0.09-0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health.