The levels of hypoxia-regulated microRNAs in plasma of pregnant women with fetal growth restriction

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level. While mostly intracellular, a portion of cellular miRNAs is released to the circulation and their level in the plasma is altered in certain pathological conditions such as cancer, and also during pregnancy. We examined the circulating levels of a set of trophoblastic miRNAs, which we recently found to be regulated by hypoxia, in the plasma of pregnant women with fetal growth restriction. As expected, pregnancy was associated with increased plasma levels of several placenta-specific miRNAs, compared to non-pregnant controls. Among pregnant women, the overall levels of miRNA species that we analyzed were increased by 1.84-fold (p ≤0.01) in plasma of women with pregnancies complicated by FGR, but decreased in FGR placentas by 24% (p ≤0.01) compared to values from uncomplicated pregnancies. Together, our results show that plasma concentration of miRNAs is regulated in pregnancy, and that FGR is associated with increased circulating miRNA levels, highlighting the need to explore plasma miRNAs as potential biomarkers for placental diseases.

Human placental trophoblasts confer viral resistance to recipient cells

“…Interestingly, many of these miRNAs, including members of the C19MC, are found in the maternal blood throughout pregnancy and rapidly decline in the first 24 h postpartum (19,20), suggesting a miRNA-based mechanism for fetal-maternal communication (13,21). Our data thus provide evidence for a unique paracrine and/or systemic function of placental trophoblasts, using exosome-mediated transport of a unique set of primate-specific effector miRNAs to directly communicate with maternal cells and possibly neighboring placental cells and regulate their immunity to viral infections.…”

“…The human C19MC is the largest known miRNA cluster, comprising 46 miRNAs that are highly expressed almost exclusively in the human placenta. Moreover, as a group, C19MC miRNAs are also the most abundant miRNA species in trophoblastic exosomes, with a strong correlation between C19MC miRNA levels in PHT cells and in PHT-derived exosomes (4,5,8,13). To date, the function of these miRNAs has remained elusive.…”

Plasma miR-221 as a Predictive Biomarker for Chemoresistance in Breast Cancer Patients who Previously Received Neoadjuvant Chemotherapy

“…Specific expression of miRNAs might correlate with particular human tumour phenotypes and biological characters such as response to treatment and prognosis [14][15][16]. Recent studies have indicated that serum and plasma contain high levels of stable miRNAs, and the expression profile of these miRNAs has shown great promise as a novel non-invasive biomarker for thediagnosisofcancerandotherdiseases [17][18][19].…”

Peripheral blood microRNAs: A novel tool for diagnosing disease?

“…Further research demonstrated that chorionic villous trophoblasts continuously released placenta-specific miRNAs into maternal circulation via exosomes (52). The level of expression of placenta-specific miRNAs in maternal peripheral blood is closely related to pre-eclampsia (PE) (3), congenital heart defects (CHD) (53), and fetal growth restriction (54).…”