Placental DNA methylation marks are associated with maternal depressive symptoms during early pregnancy

Abstract

<p>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 <a href="https://www.sciencedirect.com/topics/neuroscience/dna-methylation" title="Learn more about DNA methylation from ScienceDirect's AI-generated Topic Pages">DNA methylation</a> of candidate genes, which can influence <a href="https://www.sciencedirect.com/topics/neuroscience/blood-placenta-barrier" title="Learn more about placental barrier from ScienceDirect's AI-generated Topic Pages">placental barrier</a> function and development of the fetus. Our objective in this study was to determine <a href="https://www.sciencedirect.com/topics/neuroscience/epigenome" title="Learn more about epigenome from ScienceDirect's AI-generated Topic Pages">epigenome</a> 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 <a href="https://www.sciencedirect.com/topics/neuroscience/postpartum-depression" title="Learn more about Postnatal Depression from ScienceDirect's AI-generated Topic Pages">Postnatal Depression</a> Score ranging from 0 to 19 at gestational week 14. According to our results maternal depressive symptoms are associated with DNA methylation of 2833 <a href="https://www.sciencedirect.com/topics/neuroscience/cpg-site" title="Learn more about CpG sites from ScienceDirect's AI-generated Topic Pages">CpG sites</a>, 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 <a href="https://www.sciencedirect.com/topics/neuroscience/single-nucleotide-polymorphism" title="Learn more about single nucleotide polymorphisms from ScienceDirect's AI-generated Topic Pages">single nucleotide polymorphisms</a> associated with <a href="https://www.sciencedirect.com/topics/neuroscience/psychopathology" title="Learn more about mental disease from ScienceDirect's AI-generated Topic Pages">mental disease</a> 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.<br></p>