Tomlinson Martha Scott, Bommarito Paige A, Martin Elizabeth M, Smeester Lisa, Fichorova Raina N, Onderdonk Andrew B, Kuban Karl C K, O'Shea T Michael, Fry Rebecca C
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Laboratory of Genital Tract Biology, Department of Obstetrics and Gynecology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2017 Dec 14;12(12):e0188664. doi: 10.1371/journal.pone.0188664. eCollection 2017.
Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort. A total of n = 1,789 CpG sites, corresponding to n = 1,079 genes, displayed differential methylation (q<0.1) in relation to microorganisms. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. These data support bacteria-dependent epigenetic patterning in the placenta and provide potential insight into mechanisms that associate the presence of microorganisms in the placenta to pregnancy and neonatal outcomes. This study lays the foundation for investigations of the placental microbiome and its role in placental function.
胎盘内的微生物已被证实与不良妊娠结局以及新生儿疾病有关。胎盘炎症被认为是导致这种关联的一个因素，但其潜在的生物学机制尚未完全明确。胎盘表观基因组可能是胎盘微生物与炎症之间的中介，从而导致后代出现不良结局。在本研究中，我们利用极低孕周新生儿（ELGAN）队列收集的样本，分析了84份胎盘的全基因组DNA甲基化情况（共486,428个CpG位点），并与16种胎盘微生物进行关联分析。共有1789个CpG位点（对应1079个基因）显示出与微生物相关的差异甲基化（q<0.1）。这些发生改变的基因编码参与免疫/炎症反应的蛋白质，特别是NF-κB信号通路相关蛋白。这些数据支持胎盘内细菌依赖的表观遗传模式，并为胎盘内微生物的存在与妊娠及新生儿结局之间的关联机制提供了潜在见解。本研究为胎盘微生物组及其在胎盘功能中的作用研究奠定了基础。
