Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood

Abstract

The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student's t test, and pathway analyses were performed. In whole blood, 157 gene transcripts met statistical significance. These fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Transcripts were predominantly expressed or restricted to the fetus, the embryo, or the neonate. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts; SNP analysis demonstrated the presence of 3 fetal transcripts in maternal antepartum blood. Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. Transcriptional analysis of maternal whole blood identifies a unique set of biologically diverse fetal genes and has a multitude of clinical applications.

Noninvasive in vivo monitoring of tissue-specific global gene expression in humans

“…Plasma cellfree RNA has been investigated in cancer patients (9)(10)(11)(12) and maternal plasma (13,14) and was assumed to be packaged in apoptotic bodies that give it stability in plasma (15). Studies of maternal plasma mRNA transcripts have focused mainly on transcripts that are exclusively expressed from the placenta (16)(17)(18) or on isolated plasma samples (19) and have not attempted to comprehensively study global fetal gene expression in vivo.…”

The effect of pregnancy on production of maternal endogenous hematopoietic stem cells

“…Despite the placental barrier, there is significant evidence that fetal cells and biomarkers can be detected in maternal blood during pregnancy and for several decades after delivery. 16 However, it has also been shown that exposure of adult HSCs to human umbilical cord blood stem cells in vitro culture conditions promotes expansion and differentiation of HSCs. 17,18 This supports the hypothesis that exposure of maternal stem cells to fetal cells promotes their expansion.…”

Fetal Nucleic Acids in Maternal Circulation: A Genetic Resource for Noninvasive Prenatal Diagnosis

“…Subsequently, it was postulated that the placental-expressed mRNAs were encapsulated within a syncytiotrophoblast-derived microvesicle (STBM), which gave RNase resistance to "free" fetal RNA in maternal plasma [20]. us, with the development of RNA markers, analysis of maternal plasma allowed the noninvasive monitoring of fetal gene expression in a multitude of physiological and pathological conditions [21]. e various possible pathways by which cfDNA/cfRNA is released into circulation have been shown in Figure 1.…”