Lambertini Luca, Chen Jia, Nomura Yoko
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS One. 2015 Sep 29;10(9):e0138929. doi: 10.1371/journal.pone.0138929. eCollection 2015.
Gene-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.
Here, 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).
Our 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.
基因与环境的相互作用通过胎盘介导并塑造胎儿大脑发育。在胎儿大脑的环境决定因素中,孕期母亲的心理社会压力已被证明会对婴儿气质发展产生负面影响。这反过来可能会对婴儿的神经发育产生不良后果,并贯穿其整个生命周期。然而,对于孕期母亲心理社会压力对婴儿气质影响的潜在生物学机制知之甚少。诸如孕期母亲心理社会压力等环境应激源会激活应激反应级联,进而促使代谢率高的重要器官(如孕期的胎盘)细胞能量需求增加。应激反应级联的关键参与者是线粒体。
在此,我们检测了来自孕期压力出生队列的108份胎盘样本中线粒体编码的所有13个蛋白质编码基因的表达,该研究旨在确定子宫内暴露于孕期母亲心理社会压力对婴儿气质的影响。我们发现,蛋白质编码线粒体基因MT-ND2的表达与孕期母亲心理社会压力指标呈正相关,包括产前感知压力(β = 0.259;p回归 = 0.004;r2回归 = 0.120)、状态焦虑(β = 0.218;p回归 = 0.003;r2回归 = 0.153)、特质焦虑(β = 0.262;p回归 = 0.003;r2回归 = 0.129)和孕期焦虑总分(β = 0.208;p回归 = 0.010;r2回归 = 0.103)。同时,MT-ND2与婴儿气质指标活动水平(β = -0.257;p回归 = 0.008;r2回归 = 0.165)以及微笑和大笑(β = -0.286;p回归 = 0.036;r2回归 = 0.082)呈负相关。此外,MT-ND6与产前感知压力这一孕期母亲心理社会压力指标相关(β = -0.231;p回归 = 0.004;r2回归 = 0.120),而MT-CO2与状态焦虑(β = 0.206;p回归 = 0.003;r2回归 = 0.153)和特质焦虑(β = 0.205;p回归 = 0.003;r2回归 = 0.129)这两个孕期母亲心理社会压力指标相关。
我们的数据支持线粒体在应对孕期母亲心理社会压力中的作用,这在胎盘中得到评估,同时也表明线粒体在婴儿气质发展中具有重要作用。