【作者】 曾强；

【导师】 鲁文清；

【作者基本信息】 华中科技大学 ， 劳动卫生与环境卫生学， 2014， 博士

【摘要】 第一部分管网水THMs暴露与男性精液质量之间的关系研究目的：采用管网水中监测的四种三卤甲烷(trihalomethanes, THMs)浓度结合个体日常用水情况作为外暴露标志物,初步探讨管网水THMs暴露与男性精液质量之间的关系。方法：采用前瞻性队列研究设计,以来武汉市某综合医院生殖医学中心寻求精液分析并且居住于某大型水厂区域内的324名育龄期男性为研究对象,通过监测研究对象精液样本收集前三个月管网水中四种THMs[三氯甲烷(chloroform, TCM)、二氯一溴甲烷(bromodichloromethane, BDCM)、一氯二溴甲烷(dibromochloromethane, DBCM)和三溴甲烷(bromoform,TBM)]浓度的时间和空间分布,并结合日常生活用水活动信息和THMs不同暴露途径吸收系数评估个体的THMs外暴露水平,采用多变量线性回归分析经口和经洗澡途径暴露管网水中THMs与精液质量之间的关系。结果：多变量线性回归分析结果显示经口摄入的TTHMs、TCM和Br-THMs与降低的精子密度(P for trend分别为0.01、0.03和0.05)和精子总数(P for trend分别为0.02、0.05和0.09)之间存在显著或建议性的剂量-反应关系。此外,研究发现与第一分位数经洗澡摄入的TCM相比较,第三分位数经洗澡摄入的TCM与精子直线性存在显著的负相关(β＝2.28%,95%CI：-4.44,-0.11)。结论：本部分研究结果表明人群经口途径暴露饮用水THMs可能与降低的精子密度和精子总数有关。第二部分基础水平的血液THMs与男性精液质量和睾酮之间的关系研究目的：采用基础水平的血液THMs作为内暴露生物标志物,进一步探讨饮用水THMs暴露与男性精液质量和睾酮之间的关系。方法：采用横断面研究设计,以来武汉市某综合医院生殖医学中心寻求精液分析的401名育龄期男性为研究对象,采用固相微萃取-气相色谱法检测早晨采集的血样中四种THMs浓度评估个体基础水平的THMs内暴露水平,采用多变量线性回归分析基础水平的血液THMs与精液质量和睾酮之间的关系。结果：多变量线性回归分析结果显示与第一分位数血液BDCM相比较,第二分位数血液BDCM与精子总数之间存在显著的负相关(β=-0.13million,95%CI:-0.22,-0.03)；与第一分位数血液DBCM相比较,第二分位数血液DBCM与精子直线性之间也存在显著的负相关(β=-4.74%,95%CI:-807,-1.42);同时发现血液TCM和TTHMs与降低的精子密度之间存在建议性的剂量-反应关系(both P for trend=0.07)。此外,研究结果还显示血液DBCM与降低的血清总睾酮之间存在建议性的剂量-反应关系(P for trend=0.07)。结论：本部分研究结果进一步表明人群暴露饮用水THMs可能与降低的精子总数和精子密度有关,同时也可能与降低的睾酮有关。第三部分尿液中TCAA水平与男性精液质量之间的关系研究目的：采用尿液中三氯乙酸(trichloroacetic acid, TCAA)水平作为内暴露生物标志物,探讨饮用水消毒副产物(disinfection by-products, DBPs)暴露与男性精液质量之间的关系。方法：本部分我们开展了一项大规模横断面研究,以来武汉市某综合医院生殖医学中心寻求精液分析的2009名育龄期男性为研究对象,采用气相色谱法检测尿液中TCAA浓度评估个体经饮用水暴露DBPs的水平,采用多变量logistic回归和多变量线性回归分析尿TCAA水平与精液质量之间的关系。结果：多变量logistic回归分析结果显示与第一份位数尿TCAA水平相比,第二和第四分位数尿TCAA水平使低于精子密度正常参考值风险增加(OR=1.79,95%CI:1.19,2.69和OR=1.51,95%CI:0.98,2.31);第二和第三分位数尿TCAA水平使低于精子活力正常参考值风险增加(OR=1.46,95%CI:1.12,1.90和OR=1.30,95%CI:1.00,1.70)；第二分位数尿TCAA水平使低于精子总数正常参考值风险增加(OR=1.62,95%CI：1.04,2.55)。多变量线性回归分析显示了相似的结果。结论：本部分研究结果表明人群经饮水途径暴露DBPs可能与降低的精子密度、精子总数和精子活力有关。更多还原

【Abstract】 Part I Associaiton between exposure to THMs in tap water and semen qualityObjective:To examine the associaiton between exposure to trihalomethanes (THMs) in tap water and semen quality, using the levels of THMs in water distribution systems and personal information on routine water-use activities as external exposure surrogates.Methods:In this part we conducted a prospective study. We recruited324men who lived in a water treatment plant in Wuhan, China and presented to the Reproductive Center of a larger hospital to seek semen examination. We evaluated the participants’THM exposure based on the spatial and temporal variability of four individual THM [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM)] concentrations in tap water measured within90days preceding semen collection, personal information on ingestion and showering/bathing and the uptake factors of THMs. Multivariable linear regression was used to assess the associations of different routes of THM exposure via ingestion and showing/bathing with semen quality.Results:Multivariate linear regression analysis showed that TTHM, TCM and Br-THM uptakes via ingestion were associated with significant or suggestive decreasing trends in sperm concentration (P for trend=0.01,0.03and0.05, respectively) and sperm count (P for trend=0.02,0.05and0.09, respectively). In addition, we found that the third quartile of TCM uptake via showering/bathing was associated with declined sperm linearity compared with the first quartile of TCM uptake via showering/bathing (β=2.28%,95%CI:-4.44,-0.11). Conclusion:In this part our results suggested that THM exposure via ingestion may be associated with decreased sperm concentration and sperm count.Part II Associaitons of baseline blood THMs with semen parameters and serum total testosteroneObjective:To further examine the association of expsoure to drinking water THMs with semen quality and serum total testosterone, using baseline blood THMs as internal biomarkers.Methods:In this part we conducted a cross-sectional study. We recruited401men who presented to the Reproductive Center of a larger hospital in Wuhan, China to seek semen examination. We measured THM concentrations in morning whole blood to assess internal doses of baseline THM exposure, using solid phase micro-extraction-gas chromatography. Multivariable linear regressions were used to assess the associations of baseline blood THMs concentrations with semen parameters and serum total testosterone levels.Results:Multivariate linear regression analysis showed that the second tertile of blood BDCM level was associated with decreased sperm count (β=-0.13million,95%CI:-0.22,-0.03) compared with the lowest tertile of blood BDCM level; the second tertile of blood DBCM level was associated with declined sperm linearity compared with the lowest tertile of blood DBCM level (β=-4.74%,95%CI:-8.07,-1.42). In addition, suggestive dose-response relationships were also observed between elevated blood TCM or TTHM 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).Conclusion:In this part our results further suggested that elevated THM exposure may be associated with decreased sperm concentration, sperm count, and serum total testosterone.Part Ⅲ Assocaiton between urinary TCAA levels and semen qualityObjective:To examine the association between expsoure to drinking water disinfection by-products (DBPs) and semen quality, using urinary trichloroacetic acid (TCAA) as internal biomarkers.Methods:In this part we conducted a large-scale cross-sectional study. We recruited2009men who presented to the Reproductive Center of a larger hospital in Wuhan, China, to seek semen examination. We measured TCAA in urine as a biomarker of exposure to DBPs in chlorinated drinking water, using gas chromatography. Multivariate logistic and linear regression models were used to examine the relationship between urinary TCAA levels and semen quality.Results:Multivariate logistic regression analysis showed that men in the second and fourth quartile had an increased OR of having below-reference sperm concentration (OR=1.79,95%CI:1.19,2.69and OR=1.51,95%CI:0.98,2.31, respectively), men in the second and third quartile had an increased OR of having below-reference sperm motility (OR=1.46,95%CI:1.12,1.90and OR=1.30,95%CI:1.00,1.70, respectively), and men in the second quartile had an increased OR of having below-reference sperm count (OR=1.62,95%CI:1.04,2.55) compared to men with the lowest quartile of urinary TCAA levels. Similar results were also found in the continuous outcomes.Conclusion:In this part our results suggested that ingestion of exposure to drinking water DBPs may contribute to decreased sperm concentration, sperm count, and sperm motility in humans.更多还原