Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial Stress in Pregnancy and Infant Temperament

BackgroundGene-environment interactions mediate through the placenta and shape the fetal brain development. Between the environmental determinants of the fetal brain, maternal psychosocial stress in pregnancy has been shown to negatively influence the infant temperament development. This in turn may have adverse consequences on the infant neurodevelopment extending throughout the entire life-span. However little is known about the underlying biological mechanisms of the effects of maternal psychosocial stress in pregnancy on infant temperament. Environmental stressors such as maternal psychosocial stress in pregnancy activate the stress response cascade that in turn drives the increase in the cellular energy demand of vital organs with high metabolic rates such as, in pregnancy, the placenta. Key players of the stress response cascade are the mitochondria.ResultsHere, we tested the expression of all 13 protein-coding genes encoded by the mitochondria in 108 placenta samples from the Stress in Pregnancy birth cohort, a study that aims at determining the influence of in utero exposure to maternal psychosocial stress in pregnancy on infant temperament. We showed that the expression of the protein-coding mitochondrial-encoded gene MT-ND2 was positively associated with indices of maternal psychosocial stress in pregnancy including Prenatal Perceived Stress (β = 0.259; p-regression = 0.004; r2-regression = 0.120), State Anxiety (β = 0.218; p-regression = 0.003; r2-regression = 0.153), Trait Anxiety (β = 0.262; p-regression = 0.003; r2-regression = 0.129) and Pregnancy Anxiety Total (β = 0.208; p-regression = 0.010; r2-regression = 0.103). In the meantime MT-ND2 was negatively associated with the infant temperament indices of Activity Level (β = -0.257; p-regression = 0.008; r2-regression = 0.165) and Smile and Laughter (β = -0.286; p-regression = 0.036; r2-regression = 0.082). Additionally, MT-ND6 was associated with the maternal psychosocial stress in pregnancy index of Prenatal Perceived Stress (β = -0.231; p-regression = 0.004; r2-regression = 0.120), while MT-CO2 was associated with the maternal psychosocial stress in pregnancy indices of State Anxiety (β = 0.206; p-regression = 0.003; r2-regression = 0.153) and Trait Anxiety (β = 0.205; p-regression = 0.003; r2-regression = 0.129).ConclusionsOur data support the role of mitochondria in responding to maternal psychosocial stress in pregnancy, as assessed in placenta, while also suggesting an important role for the mitochondria in the infant temperament development.背景：基因-环境交互作用（gene-environment interactions）通过胎盘（placenta）介导，进而塑造胎儿大脑发育。在影响胎儿大脑的各类环境决定因素中，妊娠期母亲心理社会应激已被证实会对婴儿气质发育产生负面影响，进而可能对婴儿整个生命周期的神经发育造成不良后果。然而，目前对于妊娠期母亲心理社会应激影响婴儿气质的潜在生物学机制仍知之甚少。诸如妊娠期母亲心理社会应激这类环境应激源会激活应激反应级联通路，进而提升高代谢率重要器官的细胞能量需求，例如妊娠期的胎盘。应激反应级联通路的关键参与者便是线粒体（mitochondria）。 结果：本研究针对「妊娠期应激」出生队列中的108份胎盘样本，检测了线粒体编码的全部13个蛋白编码基因的表达水平，该队列旨在探究宫内暴露于妊娠期母亲心理社会应激对婴儿气质的影响。研究结果显示，线粒体编码蛋白基因MT-ND2的表达水平与妊娠期母亲心理社会应激的多项指标呈正相关，包括产前感知压力（Prenatal Perceived Stress，β=0.259；回归p值=0.004；回归r²=0.120）、状态焦虑（State Anxiety，β=0.218；回归p值=0.003；回归r²=0.153）、特质焦虑（Trait Anxiety，β=0.262；回归p值=0.003；回归r²=0.129）以及妊娠焦虑总分（Pregnancy Anxiety Total，β=0.208；回归p值=0.010；回归r²=0.103）。与此同时，MT-ND2的表达水平与婴儿气质的活动水平（Activity Level，β=-0.257；回归p值=0.008；回归r²=0.165）、微笑与大笑（Smile and Laughter，β=-0.286；回归p值=0.036；回归r²=0.082）两项指标呈负相关。此外，MT-ND6与妊娠期母亲产前感知压力指标存在关联（β=-0.231；回归p值=0.004；回归r²=0.120），而MT-CO2则与妊娠期母亲的状态焦虑（β=0.206；回归p值=0.003；回归r²=0.153）及特质焦虑（β=0.205；回归p值=0.003；回归r²=0.129）指标相关。 结论：本研究数据证实，胎盘组织中的线粒体在响应妊娠期母亲心理社会应激过程中发挥了作用，同时也提示线粒体在婴儿气质发育中具有重要意义。