Abstract
BackgroundPlacental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis.MethodologyThe concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis. Their fetal specificity was investigated by comparing the transcript concentrations in pre- and post-delivery samples and through SNP genotyping by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry. The gene expression profiles of pregnant and non-pregnant whole blood were investigated by microarray analysis. Upregulated genes in pregnant whole blood were selected for further quantitative analysis.Principal FindingsThe concentrations of the four transcripts were significantly higher in third trimester maternal whole blood than corresponding plasma without significant correlations. KISS1, PLAC4 and PLAC1 were detected in non-pregnant whole blood but not plasma. The transcripts remained detectable in some postpartum whole blood samples. The PLAC4 mRNA in maternal plasma showed fetal genotype while that in corresponding whole blood indicated both fetal and maternal contributions. Microarray analysis revealed upregulation of genes involved in neutrophil functions in pregnant whole blood including DEFA4, CEACAM8, OLFM4, ORM1, MMP8 and MPO. Though possibly pregnancy-related, they were not pregnancy-specific as suggested by the lack of post-delivery reduction in concentrations.ConclusionsMaternal plasma is preferred over maternal whole blood for placenta-derived fetal RNA detection. Most studied ‘placental’ mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as ‘illegitimate transcription’.
Highlights
The analysis of fetal nucleic acids in maternal plasma holds much promise for noninvasive prenatal diagnosis [1,2,3]
Most studied ‘placental’ mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as ‘illegitimate transcription’
Using the Spearman correlation test, no statistical significant correlation was observed between the whole blood and plasma mRNA signals for CSH1 (R2 = 0.045, P = 0.583), KISS1 (R2 = 0.003, P = 0.365), PLAC4 (R2 = 0.013, P = 0.631), and PLAC1 (R2 = 0.041, P = 0.631)
Summary
The analysis of fetal nucleic acids in maternal plasma holds much promise for noninvasive prenatal diagnosis [1,2,3]. Through the detection of the mRNA of placental expressed hormones, namely chorionic somatomammotropin hormone 1 (placental lactogen) (CSH1, NM_001317) and chorionic gonadotropin, beta polypeptide (CGB, NM_000737), the placenta was shown to be a source for fetal mRNA release into maternal plasma [5]. In 2007, Lo et al demonstrated that fetal chromosomal aneuploidy, such as trisomy 21, can be detected non-invasively from maternal plasma analysis by RNA-single nucleotide polymorphism (RNA-SNP) allelic ratio determination [9]. These studies suggest that circulating placental mRNA detection offers much opportunity for the development of noninvasive prenatal diagnostic or assessment applications. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis
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