Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring.

Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders.

The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behavior, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.

孕妇在怀孕期间承受压力会增加后代后代患精神病的风险。孕产妇压力传递到胎儿的机制尚不清楚，但是胎盘作为母亲与胎儿之间的界面，可能起关键作用。使用大鼠模型，我们调查了胎盘氧化应激在将母体社会应激对胎儿的影响中的作用以及使用纳米粒子结合的抗氧化剂治疗以防止后代不良后果的潜力。

母亲的社会心理压力增加了母亲体内循环皮质酮的水平，但胎儿却没有。孕产妇应激还会在胎盘中引起氧化应激，但在胎儿脑中却不会。使用抗氧化剂阻止氧化应激可防止雄性后代产前应激诱发的焦虑表型，并防止性别特异性的神经生物学变化，特别是海马中树突长度的减少，以及小白蛋白阳性神经元和神经元的减少。雄性后代的海马和基底外侧杏仁核中的GABA受体亚基。重要的是，许多这种作用在神经元文化中都是通过施加来自压力怀孕的胎盘条件培养基或胎儿血浆来模仿的，提示胎盘释放的分子可能介导产前压力对胎儿大脑的影响。确实，胎盘条件培养基和胎儿血浆在母体应激后均含有差异丰富的microRNA，其预测靶点富含与神经系统发育和精神疾病有关的基因。

结果强调胎盘氧化应激是传递母体社会应激对后代大脑和行为的关键介体，并提供了潜在的干预措施，以防止应激引起的胎儿对情感障碍的编程。