Sanders Alison P, Burris Heather H, Just Allan C, Motta Valeria, Svensson Katherine, Mercado-Garcia Adriana, Pantic Ivan, Schwartz Joel, Tellez-Rojo Martha M, Wright Robert O, Baccarelli Andrea A
a Department of Preventive Medicine; Icahn School of Medicine at Mount Sinai ; New York , NY USA.
Epigenetics. 2015;10(3):221-8. doi: 10.1080/15592294.2015.1006498.
Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified 6 miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2-1.5) days shorter on average (P = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.
早产是婴儿死亡的主要原因,可导致终生健康状况不佳和不良的神经发育结局。早产发生前的病理生理机制仍不清楚,表观遗传现象所起的作用在很大程度上尚未得到研究。本研究的目的是评估孕期采集的拭子所获宫颈细胞中微小RNA(miRNA)表达水平与妊娠时长之间的关联。我们分析了来自墨西哥城一个前瞻性队列中53名女性在妊娠16至19周时采集的宫颈样本,并对她们进行随访直至分娩。提取宫颈miRNA并使用NanoString nCounter分析系统对其表达进行定量。采用线性回归模型检验miRNA表达水平与分娩时孕周之间的关联,并对产妇年龄、教育程度、产次、体重指数、吸烟暴露情况以及巴氏涂片评估的炎症进行校正。我们鉴定出6种与分娩时孕周显著相关的miRNA,包括miR-21、30e、142、148b、29b和223。值得注意的是,miR-21表达每增加一倍,平均妊娠时长缩短0.9天(95%可信区间:0.2 - 1.5)(P = 0.009)。miR-30e、142、148b、29b和223表达每增加一倍,妊娠时长缩短1.0至1.6天。这些miRNA的预测靶标富含参与DNA复制和炎症过程的分子。孕期人类宫颈中特定miRNA的水平可预测分娩时的孕周,应在未来研究中作为早产风险的潜在生物标志物进行验证。