Kelly J Brunst1, Li Zhang2, Xiang Zhang2, Andrea A Baccarelli3, Tessa Bloomquist3, Rosalind J Wright4. 1. Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, Ohio. Electronic address: kelly.brunst@uc.edu. 2. Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 3. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York. 4. Department of Pediatrics and Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai, New York, New York.
Abstract
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.
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.
Authors: Audrey R Tyrka; Stephanie H Parade; Lawrence H Price; Hung-Teh Kao; Barbara Porton; Noah S Philip; Emma S Welch; Linda L Carpenter Journal: Biol Psychiatry Date: 2015-01-15 Impact factor: 13.382
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Authors: Lauren Anton; Ann DeVine; Erzsebet Polyak; Anthony Olarerin-George; Amy G Brown; Marni J Falk; Michal A Elovitz Journal: Front Physiol Date: 2019-06-06 Impact factor: 4.566
Authors: Whitney Cowell; Kelly Brunst; Elena Colicino; Li Zhang; Xiang Zhang; Tessa R Bloomquist; Andrea A Baccarelli; Rosalind J Wright Journal: Mitochondrion Date: 2021-06-06 Impact factor: 4.534