Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; School of Public Health, Occupational & Environmental Medicine, Leuven University, Leuven, Belgium.
Environ Int. 2017 Sep;106:60-68. doi: 10.1016/j.envint.2017.05.022. Epub 2017 Jun 7.
Placental mitochondrial DNA (mtDNA) content can be indicative of oxidative damage to the placenta during fetal development and is responsive to external stressors. In utero exposure to environmental pollutants that may influence placental mtDNA needs further exploration.
We evaluated if placental mtDNA content is altered by environmental pollution in newborns and identified pollutants independently associated to alterations in placental mtDNA content.
mtDNA content was measured in placental tissue of 233 newborns. Four perfluoroalkyl compounds and nine organochlorine compounds were quantified in cord blood plasma samples and six toxic metals in whole cord blood. We first applied a LASSO (least absolute shrinkage and selection operator) penalized regression model to identify independent associations between environmental pollutants and placental mtDNA content, without penalization of several covariates. Then adjusted estimates were obtained using an ordinary least squares (OLS) regression model evaluating the pollutants' association with placental mtDNA content, adjusted for several covariates.
Based on LASSO penalized regression, oxychlordane, p,p'-dichlorodiphenyldichloroethylene, β-hexachlorocyclohexane, perfluorononanoic acid, arsenic, cadmium and thallium were identified to be independently associated with placental mtDNA content. The OLS model showed a higher placental mtDNA content of 2.71% (95% CI: 0.3 to 5.2%; p=0.03) and 1.41% (0.1 to 2.8%, p=0.04) for a 25% concentration increase of respectively cord blood β-hexachlorocyclohexane and arsenic. For a 25% concentration increase of cord blood thallium, a 4.88% lower placental mtDNA content (95% CI: -9.1 to -0.5%, p=0.03) was observed.
In a multi-pollutant approach, low fetal exposure levels of environmental organic and inorganic pollutants might compromise placental mitochondrial function as exemplified in this study by alterations in mtDNA content.
胎盘线粒体 DNA（mtDNA）含量可反映胎儿发育过程中胎盘的氧化损伤程度，并对外部应激源有反应。宫内暴露于可能影响胎盘 mtDNA 的环境污染物需要进一步研究。
我们评估了新生儿环境污染物是否会改变胎盘 mtDNA 含量，并确定了与胎盘 mtDNA 含量改变独立相关的污染物。
测量了 233 名新生儿胎盘组织中的 mtDNA 含量。在脐血血浆样本中定量了四种全氟烷基化合物和九种有机氯化合物，在整个脐血中定量了六种有毒金属。我们首先应用最小绝对收缩和选择算子（LASSO）惩罚回归模型来识别环境污染物与胎盘 mtDNA 含量之间的独立关联，而不对多个协变量进行惩罚。然后，使用普通最小二乘法（OLS）回归模型评估污染物与胎盘 mtDNA 含量的关联，调整了多个协变量。
基于 LASSO 惩罚回归，氧氯丹、p,p'-二氯二苯二氯乙烯、β-六氯环己烷、全氟壬酸、砷、镉和铊被确定为与胎盘 mtDNA 含量独立相关。OLS 模型显示，脐带血β-六氯环己烷和砷浓度增加 25%，胎盘 mtDNA 含量分别增加 2.71%（95%CI：0.3 至 5.2%；p=0.03）和 1.41%（0.1 至 2.8%，p=0.04）。脐带血铊浓度增加 25%，胎盘 mtDNA 含量降低 4.88%（95%CI：-9.1 至-0.5%，p=0.03）。
在多污染物方法中，环境有机和无机污染物的胎儿低暴露水平可能会损害胎盘线粒体功能，本研究中 mtDNA 含量的改变就是例证。
