Characterization of methylation profiles in spontaneous preterm birth placental villous tissue

Abstract

AbstractPreterm birth (PTB) is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous PTB (isPTB) and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in isPTB. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique isPTB DNA methylation signature and identify loci where isPTB DNA methylation is more similar to that of term birth than the gestational age matched controls. Our results indicate the isPTB DNA methylation pattern mimics the TB methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions (DMRs) fitting the isPTB specific hypomethylation (relative to the controls) pattern were identified, indicating unusually high similarity in DNA methylation between isPTB and term birth samples. In contrast, 1718 acute histologic chorioamnionitis (AHC) specific DMRs were identified with hypermethylated DMRs in WNT and cadherin pathways when compared to isPTB and term birth samples. In these AHC DMRs, there were no significant differences between the isPTB and term birth, which indicated again, a striking level of similarly between isPTB and term birth sample sets. Taken together, these data reflect a more mature placenta than expected which may be impacting birth timing.