Abstract
BackgroundAmniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation.MethodsWe isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions.ResultsSample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity.ConclusionThe AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0138-5) contains supplementary material, which is available to authorized users.
Highlights
Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation
Transcriptomic profiles of amniotic fluid from different gestational stages After passing quality control, samples were clearly separated by gestational age group of prenatal, preterm or term, as previously defined (Fig. 1b)
Hierarchical clustering of differentially expressed genes segregated by gestational age revealed two major expression patterns: genes induced with time and genes suppressed with time (Fig. 1c)
Summary
Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation. Amniotic fluid (AF) is a dynamic mixture that both contributes to and reflects the status of the fetus [1,2,3], and has been shown to provide a screenshot into the maturational processes of fetal development [2,3,4,5]. AF from different time points in pregnancy is used to provide obstetricians and pregnant women with important information for decision-making about pregnancy management and delivery planning, such as mid-trimester. Highly sensitive methods of detection are needed to distinguish the small size and quantity of fetal DNA from maternal DNA in maternal serum samples
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