Background

Prenatal ambient fine particulate matter (PM_2.5) and maternal chronic psychosocial stress have independently been linked to changes in mithochondrial DNA copy number (mtDNAcn), a marker of mitochondrial response and dysfunction. Further, overlapping research shows sex-specific effects of PM_2.5 and stress on developmental outcomes. Interactions among PM_2.5, maternal stress, and child sex have not been examined in this context.

Methods

We examined associations among exposure to prenatal PM_2.5, maternal lifetime traumatic stressors, and mtDNAcn at birth in a sociodemographically diverse pregnancy cohort (N = 167). Mothers' daily exposure to PM_2.5 over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Lifetime exposure to traumatic stressors was ascertained using the Life Stressor Checklist-Revised; exposure was categorized as high vs. low based on a median split. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNAcn in placenta and cord blood leukocytes. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM_2.5 timing-dependent pattern of associations with mtDNAcn and explore effect modification by maternal lifetime trauma and child sex.

Results

Increased PM_2.5 exposure across pregnancy was associated with decreased mtDNAcn in cord blood (cumulative effect estimate = − 0.78; 95%CI − 1.41, − 0.16). Higher maternal lifetime trauma was associated with reduced mtDNAcn in placenta (β = − 0.33; 95%CI − 0.63, − 0.02). Among women reporting low trauma, increased PM_2.5 exposure late in pregnancy (30–38 weeks gestation) was significantly associated with decreased mtDNAcn in placenta; no significant association was found in the high trauma group. BDLIMs identified a significant 3-way interaction between PM_2.5, maternal trauma, and child sex. Specifically, PM_2.5 exposure between 25 and 40 weeks gestation was significantly associated with increased placental mtDNAcn among boys of mothers reporting high trauma. In contrast, PM_2.5 exposure in this same window was significantly associated with decreased placental mtDNAcn among girls of mothers reporting low trauma. Similar 3-way interactive effects were observed in cord blood.

Conclusions

These results indicate that joint exposure to PM_2.5 in late pregnancy and maternal lifetime trauma influence mtDNAcn at the maternal-fetal interface in a sex-specific manner. Additional studies will assist in understanding if the sex-specific patterns reflect distinct pathophysiological processes in addition to mitochondrial dysfunction.

中文翻译：

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产妇与胎儿界面的产前颗粒物暴露和线粒体功能障碍：产妇一生的创伤和儿童性别对效果的影响

背景

产前环境中的细颗粒物（PM _2.5）和母亲的慢性心理压力已独立地与线粒体反应和功能障碍的标志物线粒体DNA拷贝数（mtDNAcn）的变化联系在一起。此外，重叠的研究表明PM _2.5的性别特异性影响和压力对发育结果的影响。在此背景下，尚未检查PM _2.5，孕产妇压力和儿童性别之间的相互作用。

方法

我们在社会人口统计学上不同的妊娠队列（N  = 167）中研究了产前PM _2.5暴露，产妇终生创伤性应激源和出生时mtDNAcn的相关性。使用基于卫星的时空分解预测模型估算了妊娠期间母亲每天暴露于PM _2.5的水平。使用修订后的《生活压力源清单》确定了终生暴露于创伤性压力源；根据中位数划分，暴露分为高与低。实时定量聚合酶链反应（qPCR）用于测定胎盘和脐带血白细胞中的mtDNAcn。使用贝叶斯分布式滞后相互作用回归模型（BDLIM）对PM _2.5进行统计建模和可视化 与mtDNAcn关联的时间依赖性模式，并探讨母体终生创伤和儿童性别对效应的影响。

结果

整个妊娠期间暴露于PM _2.5的增加与脐带血中mtDNAcn的降低有关（累积影响估计值=-0.78； 95％CI-1.41，-0.16）。较高的产妇一生创伤与胎盘中mtDNAcn降低有关（β=-0.33； 95％CI-0.63，-0.02）。在报告低创伤的女性中，妊娠后期（妊娠30-38周）PM _2.5暴露增加与胎盘mtDNAcn降低显着相关。在高创伤组中未发现明显的关联。BDLIMs在PM _2.5，孕产妇创伤和儿童性别之间发现了重要的三向相互作用。具体来说，PM _2.5在报告严重创伤的母亲男孩中，妊娠25至40周之间的暴露与胎盘mtDNAcn的增加显着相关。相比之下，在同一窗口中暴露于PM _2.5的妇女与报告低创伤的母亲女孩的胎盘mtDNAcn减少显着相关。在脐带血中观察到类似的三向交互作用。

结论

这些结果表明，在妊娠晚期和产妇终生创伤中联合暴露于PM _2.5会以性别特异性的方式影响母婴界面处的mtDNAcn。进一步的研究将有助于理解是否特定性别模式除了线粒体功能障碍外还反映出不同的病理生理过程。