Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study

Abstract

Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.

Developmental programming of mitochondrial biology: a conceptual framework and review

“…The majority of in vivo human studies have used placental mtDNAcn (a marker of mitochondrial content) as the primary outcome measure, and they report an association between a range of gestational exposures and variation ( primarily a decrease) in placental mtDNAcn in offspring of women exposed to pollutants [74,79,80,93], cigarette smoke [71], intrauterine growth restriction [85,87], pre-eclampsia [94], obesity [78,88] and psychosocial stress. [72,73] There are limitations in the interpretation of altered mtDNAcn [101]; however, one study of maternal obesity exposure included multiple measures of placental mitochondrial function and reported that in conjunction with decreased mtDNAcn, there were matched decreases in other measures of mitochondrial content (citrate synthase) and OXPHOS/ ETC function and capacity (ATP levels, complex I-V protein levels and direct respiratory maximum, basal capacity) [88].…”

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

“…[44] Controlling for covariates such as recent perceived stress, resilience, depressive symptoms, and state or trait anxiety did not attenuate the relationship between ACEs and mtDNAcn. [102] The robust association between cumulative maternal lifetime stress and reduced placental mtDNAcn in a cohort of pregnant women may provide insight into fetal programming by prenatal stress. [99] While this association strengthened with the severity of abuse, it was ultimately mediated through a history of major depression.…”

Cohort profile: the Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort, a prospective preterm birth cohort in New York City

“…The strategy is robust to the correlation patterns in terms of sensitivity and specificity for identifying bad actors. The construction of weighted exposure indices can additionally be stratified by sex to test the effects of sex-specific mixtures in an integrated model, while also allowing for adjustment by additional relevant covariates 73…”