DNA methylation profiling of acute chorioamnionitis-associated placentas and fetal membranes: insights into epigenetic variation in spontaneous preterm births

Abstract

BackgroundPlacental inflammation, often presenting as acute chorioamnionitis (aCA), is commonly associated with preterm birth. Preterm birth can have both immediate and long-term adverse effects on the health of the baby. Developing biomarkers of inflammation in the placenta can help to understand its effects and potentially lead to new approaches for rapid prenatal diagnosis of aCA. We aimed to characterize epigenetic variation associated with aCA in placenta (chorionic villi) and fetal membranes (chorion and amnion) to better understand how aCA may impact processes that lead to preterm birth. This study lays the groundwork for development of novel biomarkers for aCA.MethodsSamples from 44 preterm placentas (chorionic villi) as well as matched chorion and amnion for 16 of these cases were collected for this study. These samples were profiled using the Illumina Infinium HumanMethylation850 BeadChip to measure DNA methylation (DNAm) at 866,895 CpGs across the genome. An additional 78 placental samples were utilized to independently validate the array findings by pyrosequencing.ResultsUsing a false discovery rate of < 0.15 and average group difference in DNAm of > 0.05, 66 differentially methylated (DM) CpG sites were identified between aCA cases and non-aCA cases in chorionic villi. For the majority of these 66 DM CpGs, the DNAm profile of the aCA cases as compared to the non-aCA cases trended in the direction of the blood cell DNAm. Interestingly, neutrophil-specific DNAm signatures, but not those associated with other immune cell types, were capable of separating aCA cases from the non-aCA cases.ConclusionsOur results suggest that aCA-associated placentas showed altered DNAm signatures that were not observed in the absence of aCA. This DNAm profile is consistent with the activation of the innate immune response in the placenta and/or reflect increase in neutrophils as a response to inflammation.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0234-9) contains supplementary material, which is available to authorized users.

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

“…Regarding methylation, chorionic villi, maternal decidua, fetal membranes, and embryonic tissues have a unique DNAm setting ( Robinson and Price, 2015 ). Particular alterations in DNAm signatures were observed in placentas and fetal membranes with acute chorioamnionitis ( Konwar et al, 2018 ). Moreover, many investigators have described cord blood DNAm related to prematurity and inflammation ( Liu et al, 2013 ; de Goede et al, 2017 ), but data on telomere-associated methylation are scarce.…”

Association of a placental Interleukin-6 genetic variant (rs1800796) with DNA methylation, gene expression and risk of acute chorioamnionitis

“…Ethics approval was obtained from the University of British Columbia Children’s & Women’s Research Ethics Board (H04–70488). The study cohort is based on an ongoing collection of samples for our Epigenetics in Pregnancy study (EPIC), and overlaps with samples described in previous publications related to placental DNA methylation [56–58]. Most cases were obtained in a deidentified manner with pathology and birth information available, but limited information on maternal health or demographics.…”

Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

“…Within the placenta, inflammation might alter epigenetic processes, as suggested by the finding that acute chorioamnionitis is associated with altered DNA methylation in placentas from preterm deliveries, with DNA methylation profiles consistent with activation of the innate immune response. 153 In the ELGAN cohort, placental microorganisms were associated with differential methylation within genes coding for growth and transcription factors, the immune response, and the inflammatory response, specifically the nuclear factor-κB pathway. 44 These observations support the concept that microorganisms in the placenta could influence health and development in the offspring fetal development via altered placenta epigenetic programming.…”