BioProject

Acute chorioamnionitis (aCA) is a commonly reported histologic lesion in at least 40% of spontaneous preterm deliveries. More...

Acute chorioamnionitis (aCA) is a commonly reported histologic lesion in at least 40% of spontaneous preterm deliveries. It is typically characterized by an infiltration of maternal neutrophils into the chorioamniotic membranes and is also associated with other placental inflammatory lesions such as acute intervillositis and acute villitis. DNA methylation (DNam) is an easily measurable epigenetic mark, which is more stable than mRNA. While DNAm may influence gene expression in specific cell types, it may also reflect altered cell composition. Studies have previously documented aCA-associated cellular changes primarily in the context of a polymicrobial invasion of the amniotic space. We, thus hypothesize that changes in DNAm associated with aCA will occur predominantly as a consequence of the response to infection, in particular due to alterations in the number of neutrophils and/or other alterations in cell populations inherent to the placenta. Pooled chorionic villus samples (22 aCA cases, 22 non-aCA cases) and fetal membranes (amnion and chorion) (9 aCA cases, 7 non-aCA cases) were evaluated using the Illumina EPIC array, which quantifies DNAm at >850,000 sites in the genome. We identified 66 differentially methylated sites associated with aCA (FDR <0.15, methylation difference >0.05). At the same thresholds, ~20% chorionic villi sites were also differentially methylated in chorion, but none were observed in amnion. Using publicly available datasets, we identified 2069 neutrophil-specific CpGs by differential methylation analysis. Euclidean clustering of our chorionic villi DNAm data (n=44 samples) using 2069 neutrophil-specific CpG sites largely separated aCA cases from the non-aCA cases, suggesting activation of innate immune responses in aCA-associated placentas. Overall design: Placental samples from 44 preterm placentas (chorionic villi), and matched chorion and amnion for 16 of these cases were were profiled using theInfinium HumanMethylation850 BeadChip. 4 chorionic villi samples were run in duplicates as technical replicates Less...