Abstract
The present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff < 4% were matched with a control group with normal levels of cfDNAff > 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.
Highlights
Non-invasive prenatal testing (NIPT) is a sophisticated method used worldwide for testing chromosomal abnormalities in the fetus
A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, Placenta Associated 8 (PLAC8))
The NIPT method is based on the detection of the cell-free DNA fetal fraction, in which the concentration can vary in the maternal blood from 4 to 30% [2]
Summary
Non-invasive prenatal testing (NIPT) is a sophisticated method used worldwide for testing chromosomal abnormalities in the fetus. Because the fetal component of the circulating DNA comes from the placenta, the NIPT screening test is still considered to have discordant results compared to the fetal karyotype. This is due to maternal chromosomal rearrangements or mosaicism, maternal malignancy, confined placental mosaicism, or vanishing twin pregnancies [3,4,5]. It was estimated that in humans, miRNAs modulate up to 60% of protein-coding genes in a ubiquitous manner For this reason, they are involved in several biological processes, such as differentiation, proliferation, apoptosis and development [17]. The fine-scale adjustment role of miRNAs in protein output leads, in cases of dysregulation, to human diseases, such as diverse types of cancer, several types of neurological disorders [18] and, as previously described, pregnancy complications [12,19]
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