Kee Michelle Z L, Teh Ai Ling, Clappison Andrew, Pokhvisneva Irina, MacIssac Julie L, Lin David T S, Ramadori Katia E, Broekman Birit F P, Chen Helen, Daniel Mary Lourdes, Karnani Neerja, Kobor Michael S, Gluckman Peter D, Chong Yap Seng, Huang Jonathan Y, Meaney Michael J
Translation Neuroscience, Singapore Institute for Clinical Sciences, ASTAR, Singapore 117609, Singapore.
Bioinformatics, Singapore Institute for Clinical Sciences, ASTAR, Singapore 117609, Singapore.
iScience. 2022 Aug 4;25(9):104860. doi: 10.1016/j.isci.2022.104860. eCollection 2022 Sep 16.
Prenatal maternal mental health is a global health challenge with poorly defined biological mechanisms. We used maternal blood samples collected during the second trimester from a Singaporean longitudinal birth cohort study to examine the association between inter-individual genome-wide DNA methylation and prenatal maternal depressive symptoms. We found that (1) the maternal methylome was significantly associated with prenatal maternal depressive symptoms in mothers with a female fetus; and (2) this sex-dependent association was observed in a comparable, UK-based birth cohort study. Qualitative analyses showed fetal sex-specific differences in genomic features of depression-related CpGs and genes mapped from these CpGs in mothers with female fetuses implicated in a depression-associated WNT/β-catenin signaling pathway. These same genes also showed enriched expression in brain regions linked to major depressive disorder. We also found similar female-specific associations with fetal-facing placenta methylome. Our fetal sex-specific findings provide evidence for maternal-fetal interactions as a mechanism for intergenerational transmission.
产前母亲心理健康是一项全球性的健康挑战，其生物学机制尚不明确。我们利用新加坡一项纵向出生队列研究中孕中期采集的母亲血液样本，来研究个体间全基因组DNA甲基化与产前母亲抑郁症状之间的关联。我们发现：（1）在怀有女胎的母亲中，母亲的甲基化组与产前母亲抑郁症状显著相关；（2）在一项类似的、基于英国的出生队列研究中也观察到了这种性别依赖性关联。定性分析显示，在与抑郁相关的CpG以及从这些CpG定位出的基因的基因组特征方面，怀有女胎的母亲存在胎儿性别特异性差异，这些基因与一条与抑郁相关的WNT/β-连环蛋白信号通路有关。这些相同的基因在与重度抑郁症相关的脑区中也表现出表达富集。我们还发现了与面向胎儿的胎盘甲基化组类似的女性特异性关联。我们关于胎儿性别的特异性研究结果为母婴相互作用作为代际传递的一种机制提供了证据。
