Lund Riikka J, Kyläniemi Minna, Pettersson Nina, Kaukonen Riina, Konki Mikko, Scheinin Noora M, Karlsson Linnea, Karlsson Hasse, Ekholm Eeva
FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Neurobiol Stress. 2021 Jul 31;15:100374. doi: 10.1016/j.ynstr.2021.100374. eCollection 2021 Nov.
Maternal depressive symptoms during pregnancy are a significant risk factor for adverse developmental and health outcomes of the offspring. The molecular mechanisms mediating the long-term effects of this exposure are not well understood. Previous studies have found association between prenatal exposure to maternal psychological distress and placental DNA methylation of candidate genes, which can influence placental barrier function and development of the fetus. Our objective in this study was to determine epigenome wide association of maternal depressive symptoms in early pregnancy with the placental DNA methylation. For this purpose we examined DNA methylomes of 92 placental samples by using reduced representation bisulfite sequencing. The placental samples were collected after deliveries of 39 girls and 59 boys, whose mothers had Edinburgh Postnatal Depression Score ranging from 0 to 19 at gestational week 14. According to our results maternal depressive symptoms are associated with DNA methylation of 2833 CpG sites, which are particularly over-represented in genic enhancers. The genes overlapping or nearest to these sites are functionally enriched for development of neurons and show expression enrichment in several regions of developing brain. The genomic regions harboring the DNA methylation marks are enriched for single nucleotide polymorphisms associated with mental disease trait class. Potential cellular signaling cascades mediating the effects include inflammatory and hormonal pathways. As a conclusion our results suggest that maternal depressive symptoms during early pregnancy are associated with DNA methylation marks in placenta in genes, which are important for the development and long-term health of the brain. Whether similar marks can be detected in exposed children remains to be elucidated in further studies.
孕期母亲的抑郁症状是后代发育和健康出现不良结果的一个重要风险因素。介导这种暴露长期影响的分子机制尚未完全明确。先前的研究发现，产前暴露于母亲的心理困扰与候选基因的胎盘DNA甲基化之间存在关联，这可能会影响胎盘屏障功能和胎儿发育。本研究的目的是确定孕早期母亲抑郁症状与胎盘DNA甲基化的全表观基因组关联。为此，我们使用简化代表性亚硫酸氢盐测序检测了92份胎盘样本的DNA甲基化组。这些胎盘样本是在39名女孩和59名男孩出生后收集的，他们的母亲在妊娠第14周时爱丁堡产后抑郁评分在0至19分之间。根据我们的结果，母亲的抑郁症状与2833个CpG位点的DNA甲基化有关，这些位点在基因增强子中特别富集。与这些位点重叠或最接近的基因在神经元发育方面功能富集，并在发育中的大脑的几个区域显示表达富集。含有DNA甲基化标记的基因组区域富含与精神疾病性状类别相关的单核苷酸多态性。介导这些效应的潜在细胞信号级联包括炎症和激素途径。总之，我们的结果表明，孕早期母亲的抑郁症状与胎盘中对大脑发育和长期健康至关重要的基因中的DNA甲基化标记有关。在暴露的儿童中是否能检测到类似的标记有待进一步研究阐明。
