Reproductive Endocrinology and Infertility, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Oh 44122, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA.
Hum Reprod. 2017 Dec 1;32(12):2532-2539. doi: 10.1093/humrep/dex327.
Are specific gravity (SG)-adjusted urinary concentrations of 3-(diethylcarbamoyl)benzoic acid (DCBA) associated with semen parameters among men attending an academic fertility center?
Our study did not demonstrate any association between SG-adjusted urinary DCBA concentrations and semen parameters among men attending an academic fertility center.
N,N-Diethyl-m-toluamide (DEET) is the most common active ingredient in consumer insect repellents. The recent rise in public health concerns regarding mosquito-borne diseases such as Zika, have led to an increased use of DEET insect repellents, especially among couples planning pregnancy. Animal studies have observed reproductive toxicity from DEET exposure. However, the reproductive health effects of DEET and its metabolites on human reproduction are unknown.
STUDY DESIGN, SIZE, DURATION: Between 2007 and 2015, 90 men participating in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 171 urine samples and 250 semen samples for analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The urinary concentrations of DEET, N,N-diethyl-3-hydroxymethylbenzamide (DHMB) and DCBA were quantified by isotope-dilution tandem mass spectrometry and adjusted by SG. We used linear mixed models to evaluate the association between tertiles of SG-adjusted urinary DCBA concentrations and semen parameters (semen volume, sperm concentration, total sperm count, progressive motility, total progressive motility count, normal morphology and total normal morphology count), adjusting for covariates. DEET and DHMB were not considered for analysis because of the low percentage of detectable concentrations (<7%). Effect modification by BMI and smoking status was explored.
Participants had a median age of 36 years and BMI of 27 kg/m2, and 68% had never smoked. The SG-adjusted geometric mean DCBA urinary concentration was 2.20 μg/l, with 85% detection frequency. The majority of semen parameters fell within the normal range with the exception of progressive motility, where 64% of the men had values below the WHO 2010 lower reference limits. SG-adjusted urinary DCBA concentrations were not associated with semen parameters in unadjusted or adjusted models. Men in the highest tertile of SG-adjusted urinary DCBA concentrations had comparable semen parameters to men in the lowest tertile (2.59 vs. 2.88 ml for semen volume, 47.9 vs. 45.8 million/ml for sperm concentration, 116 vs. 118 million for total sperm count, 25 vs. 24% for progressive sperm motility, and 6.1 vs. 5.8% for morphologically normal sperm). In addition, BMI and smoking status did not modify the associations.
We had a relatively small sample size with similar socioeconomic backgrounds and with overall relatively low urinary concentrations of DEET biomarkers. However, our sample size was enough to detect moderate differences with at least 80% statistical power, between the first and third tertiles of urinary DCBA concentrations. Limitations also include possible misclassification of DCBA exposure and difficulties in extrapolating the findings to the general population.
Our study found no associations between urinary concentrations of DCBA, a major metabolite of the insect repellent DEET, and semen parameters in men presenting for infertility treatment. While these results are reassuring, further studies including larger sample sizes and higher exposures are warranted.
STUDY FUNDING/COMPETING INTEREST(S): The project was financed by the National Institute of Health grants R01ES022955 and R01ES009718 and by grant P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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在参加学术生育中心的男性中，3-（二乙基氨基甲酰基）苯甲酸（DCBA）的尿比重校正浓度与精液参数是否相关？
我们的研究并未表明在参加学术生育中心的男性中，尿比重校正的 DCBA 浓度与精液参数之间存在任何关联。
N,N-二乙基间甲苯酰胺（DEET）是消费者驱虫剂中最常见的活性成分。由于对寨卡等蚊媒疾病的公共卫生担忧日益增加，DEET 驱虫剂的使用有所增加，尤其是在计划怀孕的夫妇中。动物研究观察到 DEET 暴露的生殖毒性。然而，DEET 及其代谢物对人类生殖健康的影响尚不清楚。
研究设计、规模、持续时间：2007 年至 2015 年期间，马萨诸塞州综合医院生育中心的 90 名男性参与了一项前瞻性队列研究，他们提供了 171 份尿液样本和 250 份精液样本进行分析。
参与者/材料、设置、方法：通过同位素稀释串联质谱法定量测定 DEET、N,N-二乙基-3-羟甲基苯甲酰胺（DHMB）和 DCBA 的尿液浓度，并通过比重进行调整。我们使用线性混合模型来评估 SG 调整后的尿 DCBA 浓度 tertiles 与精液参数（精液量、精子浓度、总精子计数、前向运动精子百分比、总前向运动精子计数、正常形态和总正常形态计数）之间的关联，调整了协变量。由于可检测浓度（<7%）的百分比较低，因此未考虑 DEET 和 DHMB 进行分析。探索了 BMI 和吸烟状况的效应修饰作用。
参与者的中位年龄为 36 岁，BMI 为 27kg/m2，68%的人从不吸烟。SG 调整后的 DCBA 尿浓度几何平均值为 2.20μg/l，检测频率为 85%。除了前向运动精子百分比外，大多数精液参数都在正常范围内，其中 64%的男性的数值低于世界卫生组织 2010 年的较低参考值。在未调整和调整模型中，SG 调整后的尿 DCBA 浓度与精液参数均无关联。最高 tertile 的 SG 调整后的尿 DCBA 浓度的男性与最低 tertile 的男性的精液参数相当（精液量分别为 2.59ml 和 2.88ml，精子浓度分别为 47.9 和 45.8 百万/ml，总精子计数分别为 116 和 118 百万，前向运动精子百分比分别为 25%和 24%，形态正常精子百分比分别为 6.1%和 5.8%）。此外，BMI 和吸烟状况并没有改变这些关联。
局限性-谨慎的原因：我们的样本量相对较小，具有相似的社会经济背景，总体上 DEET 生物标志物的尿浓度相对较低。然而，我们的样本量足以检测到至少 80%统计学功效的中等差异，即尿 DCBA 浓度第一 tertile 和第三 tertile 之间的差异。局限性还包括 DCBA 暴露的可能错误分类和将研究结果外推到一般人群的困难。
我们的研究发现，在参加不孕治疗的男性中，昆虫驱避剂 DEET 的主要代谢物 DCBA 的尿浓度与精液参数之间没有关联。虽然这些结果令人欣慰，但需要进一步包括更大样本量和更高暴露量的研究。
研究资金/利益冲突：该项目由美国国立卫生研究院授予的 R01ES022955 和 R01ES009718 以及国立环境卫生科学研究所（NIEHS）授予的 P30ES000002 资助。作者均无任何利益冲突。本报告中的发现和结论是作者的观点，不一定代表疾病控制和预防中心的官方立场。
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