Natural disaster stress during pregnancy is linked to reprogramming of the placenta transcriptome in relation to anxiety and stress hormones in young offspring.
Natural disaster stress during pregnancy is linked to reprogramming of the placenta transcriptome in relation to anxiety and stress hormones in young offspring.
复制标题
DOI：
10.1038/s41380-021-01123-z
复制
发表时间：
2021-11
影响因子：
11
通讯作者：
Hurd YL
中科院分区：
文献类型：
--
作者：
Nomura Y;Rompala G;Pritchett L;Aushev V;Chen J;Hurd YL
产前压力会导致长期的不良影响，增加后代患焦虑和其他情绪障碍的风险。导致这种表型的子宫内基础仍然未知。我们分析了在怀孕期间经历过飓风桑迪的妇女与在非桑迪条件下怀孕的妇女的胎盘标本的转录组。出生后，在儿童时期（3至4岁）对其后代进行纵向评估，以测量类固醇激素（头发）以及行为和情绪问题。这揭示了产前桑迪压力（PNSS）和儿童HPA功能障碍之间的显着联系，通过改变皮质醇，脱氢表雄酮（DHEA）和皮质醇：DHEA水平来证明。此外，PNSS与焦虑和攻击性显著增加相关。这些发现与胎盘转录组通过血管、免疫和内分泌基因途径的显著重组相吻合。有趣的是，许多最显着改变的基因被称为是唯一表达的胎盘细胞的合体滋养层（STB）亚型和窝藏糖皮质激素反应元件的启动子区域。最后，一些血管发育和免疫相关的胎盘基因组被发现介导PNSS和儿童表型之间的关系。总的来说，这些发现表明，怀孕期间与自然灾害相关的压力会重新编程胎盘分子特征，可能会推动压力调节和情绪健康的长期变化。对胎盘机制的进一步研究可能会阐明环境对以后生活中焦虑症风险的影响。
Prenatal stress can lead to long-term adverse effects that increase the risk of anxiety and other emotional disorders in offspring. The in utero underpinnings contributing to such phenotypes remain unknown. We profiled the transcriptome of placental specimens from women who lived through Hurricane Sandy during pregnancy compared to those pregnant during non-Sandy conditions. Following birth, longitudinal assessments were conducted in their offspring during childhood (3 to 4 years old) to measure steroid hormones (in hair) and behavioral and emotional problems. This revealed a significant link between prenatal Sandy Stress (PNSS) and child HPA dysfunction, evident by altered cortisol, dehydroepiandrosterone (DHEA), and cortisol:DHEA levels. In addition, PNSS was associated with significantly increased anxiety and aggression. These findings coincided with significant reorganization of the placental transcriptome via vascular, immune, and endocrine gene pathways. Interestingly, many of the most prominently altered genes were known to be uniquely expressed in the syncytiotrophoblast (STB)-subtype of placental cells and harbored glucocorticoid response elements in promoter regions. Finally, several vascular development and immune-related placental gene sets were found to mediate the relationship between PNSS and childhood phenotypes. Overall, these findings suggest that natural disaster-related stress during pregnancy reprograms the placental molecular signature, potentially driving long-lasting changes in stress regulation and emotional health. Further examination of placental mechanisms may elucidate the environment’s contribution to subsequent risk for anxiety disorders later in life.