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[目的]采用病例对照研究方法,观察邻苯二甲酸酯暴露对男童线粒体DNA氧化损伤及线粒体DNA拷贝数的影响,探索邻苯二甲酸酯影响男性性发育的可能机制。[方法]将2013—2014年经上海市某三级甲等医院确诊为体质性发育迟缓的8~15岁男童纳入研究,共48例病例,匹配以同一年龄段同一医院就诊于外科的正常男童60例作为对照。采用高效液相色谱-串联质谱法检测病例和对照男童尿液中邻苯二甲酸单丁酯(Mn BP)、邻苯二甲酸甲酯(MMP)、邻苯二甲酸乙酯(MEP)邻苯二甲酸(2-乙基己基)单酯(MEHP)、邻苯二甲酸(2-乙基-5羟基己基)单酯(MEHHP)、邻苯二甲酸(2-乙基-5氧己基)单酯(MEOHP)浓度。运用t检验及多元线性回归模型分析邻苯二甲酸酯水平与线粒体DNA氧化损伤、线粒体DNA拷贝数在病例和对照中的差异及两者间的关联。[结果]病例组男童尿液Mn BP、MMP、MEHP、Sum DEHP浓度显著高于正常对照组(P值分别为0.017、0.008、0.038、0.020)。病例组男童线粒体DNA拷贝数高于对照组(P=0.001),两组线粒体DNA氧化损伤水平差异无统计学意义。男童尿液MMP、MEHP、Sum DEHP浓度与线粒体DNA拷贝数存在显著正相关(P<0.05),但未发现线粒体DNA氧化损伤水平与邻苯二甲酸酯暴露水平间显著关联。[结论]体质性发育迟缓男童体内邻苯二甲酸酯暴露水平和线粒体DNA拷贝数显著升高,邻苯二甲酸酯暴露可能是线粒体功能受损的一个危险因素。
[Objective] To investigate the effects of phthalate exposure on mitochondrial DNA oxidative damage and mitochondrial DNA copy number in a case-control study to explore the possible mechanism of phthalates affecting male sexual development. [Methods] A total of 48 boys aged 8-15 years who were diagnosed as constitutional stunting at a tertiary level Hospitals in Shanghai from 2013 to 2014 were enrolled in this study. A total of 48 cases were matched to be normal in the same hospital where the same age was hospitalized 60 boys as a control. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) was used to detect the urine samples of male and female controls, including Mn BP, MEP, (2-ethylhexyl) monophthalate (MEHP), phthalic acid (2-ethyl-5-hydroxyhexyl) monoester (MEHHP), phthalic acid Monoester (MEOHP) concentration. T test and multivariate linear regression model were used to analyze the differences between phthalate level and mitochondrial DNA oxidative damage, mitochondrial DNA copy number in cases and controls, and the correlation between the two. [Results] The urine concentrations of Mn BP, MMP, MEHP and Sum DEHP in case group were significantly higher than those in normal control group (P = 0.017,0.008,0.038,0.020 respectively). The copy number of mitochondrial DNA in case group was higher than that in control group (P = 0.001). There was no significant difference in mitochondrial DNA oxidative damage between the two groups. There was a significant positive correlation between urinary MMP, MEHP and Sum DEHP concentration and mitochondrial DNA copy number (P <0.05), but no significant correlation was found between mitochondrial DNA oxidative damage level and phthalate exposure level. [Conclusion] Phthalate exposure and mitochondrial DNA copy number of boys with constitutional retardation were significantly increased. Phthalate exposure may be a risk factor of mitochondrial dysfunction.