母体孕期压力性情感状况对子代健康效应的影响及表观遗传机制研究

Pregnant women have high risk for anxiety and depression. The quantitative assessment of the effects of maternal stress on the offspring's health effects and the mechanisms involved are unclear, and epigenetic modification may play an important role. Based on the current prospective cohort platform, this study intends to explain the effect of maternal stress during pregnancy on the health effects of offspring and its mechanism through three dimensions: effect markers, effect evaluation and effect mechanism. First of all, based on the sample bank of the cohort study and the related scale score, the correlation analysis was used to explore the effect markers that could be used to quantitatively evaluate the maternal emotional status. Secondly, to clarify the effects of maternal stress conditions on the early physical growth and neurodevelopment of the offspring through the prospective cohort study and big data analysis. Finally, to explore the role of epigenetic regulation mechanism during the maternal emotional impact on the early growth and development of the offspring using epigenomics. The results will further clarify the stress status of pregnant women in China and reveal their effects and mechanisms on the health effects of offspring in order to contribute to the promotion of mental health of pregnant women and reduce the burden of disease in children.

妊娠期妇女是焦虑抑郁症状高发人群。母体孕期压力性情感状况影响子代健康效应的定量评估方法及相关机制尚不明确，胎盘表观遗传学修饰可能发挥重要作用。本课题拟在当前开展的前瞻性队列平台的基础上，通过效应标志物测定、效应评价、效应机制研究三个维度阐释母体孕期压力性情感状况对子代健康效应的影响及机制。首先，基于队列样本库并结合相关量表评分，运用相关性分析，探索可以用于定量评估妊娠期母体压力性情感状况的效应标志物；其次，通过前瞻性队列研究，借助大数据分析，阐明妊娠期母体压力性情感状况对子代早期体格生长和神经发育的影响；最后，利用组学分析技术，筛选并验证胎盘表观遗传学标志物，探讨母体各种压力性情感状况对子代早期生长发育影响的表观遗传学调控机制。研究结果将进一步明确我国妊娠期妇女压力性情感状况，揭示其对子代健康效应的影响及机制，以期能够为促进孕妇心理健康和降低儿童疾病负担做出贡献。

根据健康与疾病的发育起源(DOHaD)理论，孕期母体压力可能对后代的健康产生影响。本项目基于出生队列设计，评估整个妊娠期的母体压力性情感状况对子代早期体格生长和神经发育的影响及其生物学机制。采用相关量表对母体在整个孕期的妊娠压力与焦虑抑郁症状分别进行分数评定；通过相关性分析，探寻多巴胺代谢产物作为效应标志物的可能性。分析母体妊娠压力和焦虑抑郁症状影响胎儿宫内生长发育的相对风险、暴露关键窗口期及相应的暴露-反应关系；分析母体妊娠压力与焦虑抑郁症状对婴幼儿神经发育的影响及可能的暴露-反应关系；组学筛选并验证 DNA 甲基化差异表达区，探寻相关的表观遗传标志物。首次发现孕晚期睡眠潜伏期在孕晚期客观严重负性事件与新生儿出生体重之间的中介作用；发现孕晚期皮质醇浓度受应激压力影响最大，与应激压力评分呈正相关；阐明孕妇压力性情感因素对婴幼儿 0~24 月龄的体格生长以及心理行为发育均有影响，且效应大小和方向因压力性情感因素的性质不同而异，心理行为发育的效应更明显；发现胎盘IGF2和BID基因 DNA甲基化水平与胎儿生长发育相关。项目研究结果将进一步明确我国妊娠期妇女压力性情感状况，揭示其对子代健康效应的影响及机制，有望能够为促进孕妇心理健康和降低儿童疾病负担做出贡献。