Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4; Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
Neurosci Biobehav Rev. 2015 Jan;48:70-91. doi: 10.1016/j.neubiorev.2014.11.013. Epub 2014 Nov 24.
Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in miRNA expression and DNA methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety- or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.
在过去几十年的研究中，有令人信服的证据表明，孕妇在怀孕期间经历的压力会对母亲和她的孩子未来的心理健康产生长期影响。最近的人类流行病学和动物研究表明，子宫内或生命早期的压力经历可能会增加神经和精神疾病的风险，这可能是通过改变表观遗传调控实现的。表观遗传机制，如 miRNA 表达、DNA 甲基化和组蛋白修饰，容易因应激体验和恶劣环境因素而发生变化。表观遗传调控的改变可能会影响胎儿的内分泌编程和大脑发育，跨越多个世代。然而，直到最近，人们才开始更多地关注压力的可能跨代效应。在这篇综述中，我们讨论了人类研究和动物模型中应激暴露的跨代表观遗传遗传的证据。我们强调了产前应激暴露、胎盘和大脑中 miRNA 表达和 DNA 甲基化的相关变化以及与精神分裂症、注意力缺陷多动障碍、自闭症、焦虑或抑郁相关障碍风险增加之间的复杂相互作用。基于现有证据，我们提出，产前应激通过表观遗传改变的产生，成为影响晚年心理健康的最有力因素之一。考虑祖先和产前应激对终身健康轨迹的影响对于改善支持健康发展和成功老龄化的策略至关重要。
