Associations Between Exposure To Disinfection By-products Of Drinking Water And Semen Quality In Healthy Chinese Men

Part One: The impacts of water-use activities and other factors on blood trihalomethanes,urine haloacetic acid,and semen quality parametersObjectives: To evaluate whether demographic characteristics,lifestyle factors(e.g.,smoking and drinking),and water-use activities influenced the concentrations of exposure biomarkers of disinfection by-products(DBPs)[i.e.blood trihalomethanes(THMs),urinary haloacetic acids(HAAs)] and semen quality parameters.Methods: From April to December 2017,1,319 healthy men screened as potential sperm donors were recruited from the Hubei Province Human Sperm Bank.Each participant completed a questionnaire,which collected data on basic demographic characteristics,health history,occupational exposure,smoking and drinking habits,and daily water-use activities.A single blood sample was collected at baseline to quantify blood concentrations of four THMs: chloroform(TCM),bromodichloromethane(BDCM),dibromochloromethane(DBCM)and bromoform(TBM).Bromo-trihalomethanes(Br-THMs)are the sum of the blood concentrations of BDCM,DBCM and TBM.Total trihalomethanes(TTHMs)are the sum of the blood concentrations of TCM and Br-THMs.Urine and semen samples were repeated collected at baseline and follow-ups over a 90-day period(spermatogenesis stage,meiosis stage,forward motor ability stage,epididymis storage stage,mature sperm cell stage),which were used to quantify HAAs [i.e.,dichloroacetic acid(DCAA)and trichloroacetic acids(TCAA)]and semen quality parameters,respectively.Intraclass correlation coefficients(ICCs)were estimated to evaluate the variability of urinary HAAs and semen quality parameters.Univariable and multivariable regression models were used to determine the impact of water-use activities and other factors on blood THMs,urine HAAs,and semen quality parameters.Results: The detection rates of blood TCM,DBCM,and urinary TCAA were all above 80%.Urinary DCAA exhibited high within-individual variability(ICC < 0.01),indicating poor reproductivity;thus,DCAA was not included in the subsequent analyses.Fair-to-good reproducibility(ICC > 0.40)was observed for urinary TCAA,sperm concentration,total count,progressive motility,and total motility.Multivariable regressions showed that the sampling season had a significant impact on blood TCM,BDCM,DBCM,TBM,Br-THMs,TTHMs and urine TCAA.Bathing frequency was positively associated with blood concentrations of TBM,Br-THMs and TTHMs;men with a habit of having cold water bath were at a higher level of blood TCM than those with the habit of having hot water both.Age,body mass index(BMI),and individual monthly income were inversely associated with uriary concentrations of TCAA.Men who drank tap water without purification device had a higher urinary level of TCAA than those who did not.Sampling season also had a significant impact on semen quality parameters.Additionally,total sperm count and concentration were positively associated with age and education level,and the progressive motility and total motility of sperm were inversely associated with age and bathing time.Compared with non-smokers,current smokers showed a lower total sperm count.Sperm concentration was lower among men who had a drinking habit than men never or rarely drank alcohol.Conclusions: Blood THMs was influenced by sampling season,and bathing frequency and temperature;urinary TCAA was influenced by age,BMI,monthly income,sampling season,and tap-water consumption.Semen quality parameters were affected by age,education level,smoking and drinking status,and bathing duration.Part Two: Associations between blood trihalomethanes and semen quality in healthy men screened as sperm donorsObjectives: To evaluate the associations between blood THMs and repeated measurements of semen quality parameters among 1199 healthy men screened as potential sperm donors.Methods: The recruitment of participants and the collection of blood and semen samples in this part has been described in detail in part one.A total of 1199 subjects who provided 5,213 semen samples were finally included in the analyses of this part.Blood concentrations of TCM,BDCM,Br-THMs and TTHMs were divided into tertiles.The detection rates of DBCM and TBM were 59.7% and 41.8%,respectively;thus,three-level categorical variables were constructed by classifying detected values < LOD as the lowest exposure group,and then dividing the detectable values equally(at the median)as the middle-and high-exposure groups.Multivariable linear regression models were used to estimate the cross-sectional associations of tertiles of blood THM concentrations with semen quality parameters measured at baseline,and mixed-effect models were used to estimate the longitudinal associations accounting for repeated measures of semen quality,adjusting relevant confounding factors.Results: Compared with the lowest tertile of blood TCM,the total sperm count,total motility and progressive motility of men in the highest tertile of blood TCM decreased by 20.2%(95% CI:-31.6,-6.9),4.9%(95% CI:-9.2,-0.5),and 5.2%(95% CI:-9.6,-0.5)respectively.The men in the highest tertiles of Br-THMs had a lower sperm count of 17.96%(95% CI:-29.9,-4.1)than men in the lowest tertile.The sperm count and the concentration of men in the highest tertile of TTHMs decreased by 21.3%(95% CI:-32.9,-8.0)and 12.5%(95% CI:-22.0,-2.1),respectively.Men in the highest tertile of chloroform and dibromochloromethane had a lower sperm count of 15.3%(95% CI:-24.3,-5.2)and 10.3%(95% CI:-19.7,0.5),respectively,than men in the lowest tertile in the longitudinal,repeated measure analysis.Conclusions: Exposure to THMs from drinking water may be associated with some semen quality parameters in healthy adult men,especially the inverse association between blood TCM and total sperm count.Part Three: Associations between urinary concentrations of TCAA and semen quality parametersObjectives: To investigate the associations between TCAA exposure and repeated measurements of semen quality,using average concentrations of urinary TCAA as internal exposure biomarkers.Methods: The recruitment of participants and the collection of urine and semen samples in this part has been described in detail in part one.A total of 1,305 study participants who provided 3,367 urine samples and 5,289 semen samples were included in the analyses of this part.Urinary TCAA showed a high detection rate and was thus divided into tertiles.Multivariable linear regressions were used to evaluate the associations between average urinary TCAA concentrations and average semen quality parameters.Mixed-effect models were used to estimate the associations of average urinary TCAA concentrations and repeated measurements of semen quality measurements,adjusting for potential confounders.Results: After adjusting for urinary creatinine and other confounding factors,there was no evidence of associations between average urinary TCAA concentrations and average semen quality parameters(p> 0.05).Mixed-effect models showed that men in the highest tertile of TCAA had a higher sperm count of 17.3%(95% CI: 3.2,33.1)than the men in the lowest tertile.Conclusions: There was no consistent evidence showing that exposure to TCAA from drinking water was associated with semen quality in healthy adult men.Part Four: Associations between DBP exposure,oxidative stress,and semen qualityObjectives: To evaluate the associations between DBP internal exposure biomarkers(i.e.,blood THMs and urinary TCAA),urinary 8-hydroxy-2-deoxyguanosine(8-OHdG)concentrations,and semen quality parameters.Methods: The recruitment of participants and the collection of blood,urine,and semen samples in this part has been described in detail in part one.Variability of 8-OHdG was assessed by calculating the ICCs among a subgroup of 104 subjects who provided 390 urine samples.The concentrations of 8-OHdG in within-individual pooled urine samples was determined to characterize participants’ oxidative stress status.Multivariable linear regressions were used to evaluate the associations of blood THMs and average urinary TCAA with and 8-OHdG in pooled urine,and the association of 8-OHdG in pooled urine with average semen quality parameters.Results: Urinary 8-OHdG showed high within-individual variability(ICC = 0.16).After adjusting for urinary creatinine and other confounding factors,men in the highest tertile of blood TBM,Br-THMs,TTHMs and urine TCAA had a lower 8-OHdG of 7.5%(95%CI:-0.9,16.6),10.7%(95% CI: 2.4,19.7),16.3%(95% CI: 7.6,25.8),and 10.7%(95% CI: 1.8,20.2),respectively,than the men in the lowest tertiles.There was no evidence of associations between urinary 8-OHdG and semen quality parameters(all p> 0.05).Conclusions: Exposure to DBPs from drinking water was positively associated with urinary 8-OHdG.However,there is no evidence of associations between urine 8-OHdG and semen quality parameters.