Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 11000, Mexico.
Departamento de Medicina Traslacional, Instituto Nacional de Perinatología, Mexico City 11000, Mexico.
Int J Mol Sci. 2020 May 20;21(10):3597. doi: 10.3390/ijms21103597.
Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP ( = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP ( = 39), including 9 lncRNAs with a high correlation degree ( < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.
子痫前期 (PE) 和宫内生长受限 (IUGR) 是围产期发病率和死亡率的主要原因。这些妊娠疾病与胎盘功能障碍有关,具有相似的病理生理特征。本研究旨在比较包括 mRNA 和 lncRNA 在内的来自四个研究组(PE、IUGR、PE-IUGR 和正常妊娠(NP))孕妇的胎盘基因表达谱。在分娩时获得胎盘组织进行基因表达微阵列分析,并使用 RTq-PCR 进行验证。差异基因表达分析显示,与 NP 相比,IUGR 样本的转录本变化最大(=461;314 个 mRNAs:252 个上调,62 个下调;133 个 lncRNAs:36 个上调,98 个下调)。我们还检测到一组与 NP 相比,PE 和 IUGR 样本之间共有的差异表达转录本(=39),包括 9 个具有高相关性(<0.05)的 lncRNAs。这些共享转录本的功能富集表明,细胞因子信号通路、蛋白质修饰和 JAK-STAT 级联的调节在两种胎盘缺血性疾病中过度表达。这些发现有助于对胎盘缺血的分子特征进行描述,表明与 PE 和 IUGR 病理生理学相关的常见表观遗传调控。