Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL Research, Via Fontana Candida1, 00078 Monte Porzio Catone, Rome, Italy.
Department of Medicine and Surgery, University of Parma, via A. Gramsci 14, 43126 Parma, Italy.
Int J Environ Res Public Health. 2020 Mar 13;17(6):1880. doi: 10.3390/ijerph17061880.
In recent decades, there has been an increase in male infertility, and in many cases, the etiology remains unclear. Several studies relate male hypo-fertility to xenobiotic exposure, even if no data exist about multiple exposure at the environmental level.
The study involved 86 males with diagnosis of idiopathic male infertility (IMI), and 46 controls with no alteration in sperm characteristics. Seminal plasma (SP) and urine samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify biomarkers of exposure (the main metabolites of benzene, toluene, 1,3-butadiene, 3-monochloropropanediol, styrene, and naphthol) and effect (oxidized products of nucleic acids).
Biomarker concentrations were similar in subjects with IMI and controls even if a stronger correlation between biomarkers of exposure and effects were observed in SP. Data show that, both in SP and urine, most metabolites were inter-correlated, indicating a simultaneous co-exposure to the selected substances at the environmental level. Principal component analysis showed in SP the clustering of mercapturic acids indicating a preferential metabolic pathway with Glutathione (GSH) depletion and, consequently, an increase of oxidative stress. This result was also confirmed by multivariable analysis through the development of explanatory models for oxidized products of nucleic acids.
This study highlights how oxidative stress on the male reproductive tract can be associated with a different representation of metabolic pathways making the reproductive tract itself a target organ for different environmental pollutants. Our results demonstrate that SP is a suitable matrix to assess the exposure and evaluate the effects of reproductive toxicants in environmental/occupational medicine. The statistical approach proposed in this work represents a model appropriate to study the relationship between multiple exposure and effect, applicable even to a wider variety of chemicals.
近几十年来，男性不育症的发病率有所上升，而在许多情况下，病因仍不清楚。一些研究将男性生育力低下与外源性物质暴露联系起来，即使在环境水平上没有关于多种暴露的数据。
本研究纳入了 86 名诊断为特发性男性不育症（IMI）的男性和 46 名精子特征无改变的对照者。采用液相色谱串联质谱法（LC-MS/MS）分析精液（SP）和尿液样本，以定量评估暴露标志物（苯、甲苯、1,3-丁二烯、3-氯-1,2-丙二醇、苯乙烯和萘酚的主要代谢物）和效应标志物（核酸氧化产物）。
即使在 SP 中观察到暴露标志物和效应标志物之间更强的相关性，但 IMI 患者和对照组的生物标志物浓度相似。数据表明，无论是在 SP 还是尿液中，大多数代谢物之间都存在相关性，这表明在环境水平上同时存在对所选物质的共同暴露。主成分分析显示，SP 中的巯基尿酸聚类表明存在优先的代谢途径，即谷胱甘肽（GSH）耗竭，进而导致氧化应激增加。多变量分析通过建立核酸氧化产物的解释模型，也证实了这一结果。
本研究强调了男性生殖道的氧化应激如何与代谢途径的不同表现相关联，使生殖道本身成为不同环境污染物的靶器官。我们的结果表明，SP 是评估环境/职业医学中生殖毒物暴露和效应的合适基质。本工作中提出的统计方法代表了一种适用于研究多种暴露与效应之间关系的模型，即使对于更多种类的化学物质也适用。
