Soluble inflammatory mediators induce transcriptional re-organization that is independent of dna methylation changes in cultured human chorionic villous trophoblasts

The studies proposed here were undertaken to test the hypothesis that, under specific circumstances (e.g., a strong enough inflammatory stimulus), genes that are repressed at the maternal-fetal interface via DNA methylation might be de-methylated, allowing either a maternal immune response to the semi-allogenic fetus or the onset of early labor. Chorionic trophoblasts (CT) were isolated from fetal membranes, followed by incubation with medium from LPS-activated PBMC or resting PBMC medium for 2 h. RNA and DNA were isolated from the cells for RNA-seq and DNA methylation studies. Two hrs after being exposed to conditioned medium from LPS-activated PBMC, CT showed differential expression of 114 genes, all but 2 of which showed higher expression in the stimulated cells than is the unstimulated cells. We also identified 318 differentially methylated regions (DMRs) that associated with 306 genes (155 protein coding genes) in the two groups, but the observed methylation changes had negligible impact on the observed transcriptional changes in CT. CT display complex patterns of transcription in response to inflammation. DNA methylation does not appear to be an important regulator of the observed transcriptional changes.