BACKGROUND Disrupted placental functioning due to stress can have lifelong implications. Cumulative stress and trauma are likely to have lasting impacts on maternal physiological functioning and offspring development, resulting in increased risk for later-life complex disorders for which racial disparities exist. METHODS This study examined the association between maternal lifetime stress and placental mitochondrial DNA mutational load in an urban multiethnic cohort. Maternal lifetime exposure to stressful events was assessed using the validated Life Stressor Checklist-Revised. Whole mitochondrial DNA sequencing was performed and mutations were determined for 365 placenta samples with complete exposure and covariate data. Multivariable regression was used to model maternal lifetime stress in relation to placental mitochondrial DNA mutational load. Racial/ethnic differences were examined by cross-product terms and contrast statements. Gene-wise analyses were conducted. RESULTS We identified 13,189 heteroplasmies (Phred score > 10,000, minor allele frequency < 0.5, number of mutant reads > 1). Women experiencing increased psychosocial stress over their lifetime exhibited a higher number of total placental mitochondrial mutations (β = .23, 95% confidence interval = .03 to .42) and heteroplasmic mutations (β = .18, 95% confidence interval = .05 to .31) but not homoplasmic mutations (β = -.008, 95% confidence interval = -.03 to .01); the strongest associations were observed among Black women and genes coding for NADH dehydrogenase and cytochrome c oxidase subunits. CONCLUSIONS Cumulative maternal lifetime stress is associated with a greater mitochondrial mutational load, particularly among Black women. The impact of racial/ethnic differences in mutational load on placental function directly affecting offspring development and/or leading to chronic disease disparities warrants further investigation.

中文翻译：

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城市多种族队列中孕产妇终生压力与胎盘线粒体 DNA 突变之间的关联

背景技术由于压力导致的胎盘功能中断可能具有终身影响。累积的压力和创伤可能会对母体生理功能和后代发育产生持久影响，从而导致存在种族差异的晚年复杂疾病的风险增加。方法 本研究在一个城市多种族队列中检查了母亲一生的压力与胎盘线粒体 DNA 突变负荷之间的关联。使用经验证的生活压力源检查表-修订版评估了孕产妇一生中对压力事件的暴露情况。对 365 个胎盘样本进行了全线粒体 DNA 测序，并确定了具有完整暴露和协变量数据的突变。多变量回归用于模拟与胎盘线粒体 DNA 突变负荷相关的母体终生压力。通过交叉产品术语和对比陈述检查种族/民族差异。进行了基因分析。结果 我们确定了 13,189 个异质性（Phred 评分 > 10,000，次要等位基因频率 < 0.5，突变读数 > 1）。在其一生中经历过增加的社会心理压力的女性表现出更多的胎盘线粒体突变（β = .23，95% 置信区间 = .03 至 .42）和异质突变（β = .18，95% 置信区间 = .05）至 .31）但不是同质突变（β = -.008，95% 置信区间 = -.03 至 .01）；在黑人女性和编码 NADH 脱氢酶和细胞色素 c 氧化酶亚基的基因中观察到最强的关联。结论 累积的母体终生压力与更大的线粒体突变负荷相关，特别是在黑人女性中。突变负荷的种族/民族差异对胎盘功能的影响直接影响后代发育和/或导致慢性疾病差异，值得进一步研究。