Global Gene Expression Analysis of Term Amniotic Fluid Cell-Free Fetal RNA. Homo sapiens

The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid. Overall design: This was a prospective whole genome microarray study comparing eight amniotic fluid samples collected from eight women at term who underwent prelabor cesarean delivery and eight second-trimester amniotic fluid samples from routine amniocenteses. A functional annotation tool was used to compare tissue expression patterns in term and second-trimester samples. Pathways analysis software identified physiologic systems, molecular and cellular functions, and upstream regulators that were significantly overrepresented in term amniotic fluid.

本研究旨在通过对比足月妊娠与妊娠中期羊水上清液的功能基因组分析，鉴定足月妊娠羊水无细胞胎儿RNA（cell-free fetal RNA）的组织表达模式及富集的生物学通路。本研究共鉴定出2871个显著差异调控基因。与妊娠中期的脑组织及胚胎神经细胞相比，足月妊娠羊水的组织表达分析显示其富集唾液腺、气管及肾脏相关转录本。对足月妊娠时上调的基因进行功能分析发现，其调控通路与产后适应高度特异性相关，涵盖免疫功能、消化、呼吸、碳水化合物代谢及脂肪生成。正常分娩涉及的两大关键过程——炎症反应与前列腺素合成，在足月妊娠羊水中也被激活。
总体设计：本研究为一项前瞻性全基因组微阵列（whole genome microarray）研究，对比了8例足月临产前接受剖宫产的孕妇的羊水样本，以及8例来自常规羊膜穿刺术（routine amniocentesis）的妊娠中期羊水样本。研究采用功能注释工具对比足月与妊娠中期样本的组织表达模式，并通过通路分析软件鉴定出在足月妊娠羊水中显著富集的生理系统、分子与细胞功能，以及上游调控因子。