Placenta-Derived Fetal Specific mRNA Is More Readily Detectable in Maternal Plasma than in Whole Blood

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’.

Aberrant Concentrations of Liver-Derived Plasma Albumin mRNA in Liver Pathologies

“…Some researchers have suggested that ALB mRNA in blood originates from malignant or nonmalignant hepatocytes that have entered the peripheral circulation (14,15,18,20 ); however, Muller et al (16 ) reported that peripheral mononuclear cells can be induced to produce ALB mRNA. Indeed, previous reports have indicated that certain supposedly organ-specific transcripts detectable in the circulation may in fact be derived from other cell populations, such as hematopoietic cells (27,37 ), owing to illegitimate gene transcription (24,38 ).…”

Increased Levels of Cell-Free Human Placental Lactogen mRNA at 28–32 Gestational Weeks in Plasma of Pregnant Women With Placenta Previa and Invasive Placenta

“…7 Additionally, cell-free human placental lactogen (hPL) messenger RNA (mRNA), which is entirely produced by trophoblast cells, is detectable in maternal plasma form early stages of pregnancy and undetectable postdelivery. [8][9][10] Interestingly, cell-free hPL mRNA has been reported to be increased in pregnancies complicated by placenta previa and invasive placenta. [11][12][13] Yet, the mechanisms of increasing hPL observed in patients with invasive placenta are not clear; it is interesting to note that hPL has also been reported to be decreased in pregnancies complicated by preeclampsia, 14 where there is an abnormally shallow invasion of the trophoblast into the myometrium.…”

Circulating mRNA for the PLAC1 Gene as a Second Trimester Marker (14-18 Weeks' Gestation) in the Screening for Late Preeclampsia

“…We dosed PLAC1 in the second trimester since it is definitely detectable at that time [25] and also because the low degree or absence of placental insufficiency typical of late PE makes predicting late PE in the first trimester quite challenging. Some biochemical markers like PlGF, however, when combined with a panel of specific markers, yielded a more promising result in late PE screening, also in the first trimester [23] .…”