Department of Occupational and Environmental Health, School of Public Health, Shanxi Medical University, Xinjiannan Road 56, Taiyuan, 030001, Shanxi, China.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722W. 168th Street, New York, NY, 10032, USA.
Environ Pollut. 2020 Oct;265(Pt B):114594. doi: 10.1016/j.envpol.2020.114594. Epub 2020 Apr 16.
Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy is a risk factor for adverse neurobehavioral development outcomes. Mitochondrial DNA are sensitive to environmental toxicants due to the limited ability of repairing. The change of mitochondrial DNA copy number (mtDNAcn) might be a biologically mechanism linking PAH exposure and children's neurobehavioral impairment. Our aims are to explore whether PAH metabolites in maternal urine were associated with children's neurobehavioral development at 2 years old and umbilical cord blood mtDNAcn, and whether mtDNAcn was a mediator of PAH-related neurobehavioral development. We included 158 non-smoking pregnant women from Taiyuan City, Shanxi Province. Maternal urinary eleven PAH metabolites were detected by high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). MtDNAcn in cord blood was detected by real time quantitative polymerase chain reaction (RT-PCR). Children's neurodevelopment was measured by Gesell Developmental Schedules (GDS) when children were two years age. Generalized linear models and restricted cubic spline models were applied to assess the relationships between PAH metabolites in maternal urine and GDS scores and mtDNAcn. A mediation analysis was also conducted. Generalized linear models showed the relationships of sum of PAH metabolites (Σ-OHPAHs) in maternal urine with decreased motor score, and Σ-OHPAHs with increased mtDNAcn (p for trend < 0.05). Urinary levels of Ln (Σ-OHPAHs) increased one unit was related to a 2.08 decreased in motor scores, and Ln (Σ-OHPAHs) increased one unit was related to 0.15 increased in mtDNAcn. Mediation analysis did not find mtDNAcn can be a mediator between PAH metabolites and neurobehavioral development. Our results suggest that prenatal exposure to PAH decreased children's neurobehavioral development scores and increased mtDNAcn. And reducing exposure to PAH during pregnancy will benefit to improving neurobehavioral development in children. In our present cohort study, sum of PAH metabolites in urine of pregnant women were related with motor score and were positively associated with umbilical cord blood mtDNA copy number.
孕期多环芳烃（PAHs）暴露是不良神经行为发育结局的危险因素。线粒体 DNA 由于修复能力有限，对环境毒物敏感。线粒体 DNA 拷贝数（mtDNAcn）的变化可能是将 PAH 暴露与儿童神经行为损伤联系起来的生物学机制。我们的目的是探讨母体尿液中 PAH 代谢物是否与 2 岁儿童神经行为发育以及脐带血 mtDNAcn 有关，以及 mtDNAcn 是否是 PAH 相关神经行为发育的中介。我们纳入了来自山西省太原市的 158 名不吸烟孕妇。采用高效液相色谱串联质谱法（HPLC-MS/MS）检测母体尿液中 11 种 PAH 代谢物。采用实时定量聚合酶链反应（RT-PCR）检测脐带血 mtDNAcn。当儿童 2 岁时，采用 Gesell 发育时间表（GDS）测量儿童神经发育情况。采用广义线性模型和限制立方样条模型评估母体尿液中 PAH 代谢物与 GDS 评分和 mtDNAcn 之间的关系。还进行了中介分析。广义线性模型显示，母体尿液中Σ-OHPAHs 总和与运动评分降低有关，Σ-OHPAHs 与 mtDNAcn 增加有关（趋势 p<0.05）。母体尿液中 Ln（Σ-OHPAHs）增加一个单位与运动评分降低 2.08 分相关，Ln（Σ-OHPAHs）增加一个单位与 mtDNAcn 增加 0.15 分相关。中介分析未发现 mtDNAcn 可作为 PAH 代谢物与神经行为发育之间的中介。我们的结果表明，产前暴露于 PAH 会降低儿童的神经行为发育评分并增加 mtDNAcn。减少孕期 PAH 暴露将有利于改善儿童的神经行为发育。在我们目前的队列研究中，母体尿液中 PAH 代谢物总和与运动评分有关，与脐带血 mtDNA 拷贝数呈正相关。
