Clusterin and Its Potential Regulatory microRNAs as a Part of Secretome for the Diagnosis of Abnormally Invasive Placenta: Accreta, Increta, and Percreta Cases

Abstract

Magnetic resonance imaging (MRI) and ultrasound methods used for the diagnosis of an abnormally invasive placenta (AIP) have a wide range of sensitivity (Se, 33–93%) and specificity (Sp, 71–100%) levels, which results in a high risk of unfavorable maternal and perinatal outcomes. The relevance of optimizing the diagnosis of AIP is beyond doubt. Given the epigenetic nature of trophoblast invasion, we aimed to quantitate microRNAs and proteins of their target genes that are potentially associated with AIP in blood plasma samples from 64 pregnant women at gestation weeks 30–34 by reverse transcription coupled with polymerase chain reaction (RT-PCR) and Western blotting, respectively. Statistically significant increases in the expression levels of hsa-miR-17-5p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, and hsa-miR-320a-3p were revealed in the groups of women with AIP (accreta, increta, percreta) relative to the group of women with scars on the uterus or to the group with placenta previa. Opposite changes in the expression level of “gene–target protein/miRNA” pairs were found for the α-subunit of the clusterin secretory form and any of the hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-320a-3p, and hsa-miR-17-5p in all cases of AIP. The developed logistic regression models to diagnose AIP cases of various severity gave Se values of 88.8–100% and Sp values of 91.6–100% using a combination of hsa-miR-21-5p, hsa-miR-92a-3p, hsa-miR-320a-3p, or clusterin levels.

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

“…Disruption of this process can lead to EMT, which can in turn lead to carcinomatosis [45,46]. EMT can be induced by many oncogenic pathways, such as transforming growth factor-β (TGF-β), MAPK, Ras pathway, ERK, PI3K/Akt signaling, and cyclin kinase inhibitor p27mediated signaling [47][48][49]. Reduction or lack of CDH1 expression has been observed in tumors and metastases of many organs, including the gastrointestinal tract, urinary tract, uterus, ovary, thyroid gland, prostate, and skin [43,45,50,51].…”

“…Timofeeva et al attempted to develop diagnostic methods for the abnormally invasive placenta (AIP), which includes placenta accreta, percreta, and increta [49]. As we know, trophoblasts require EMT to invade the decidua, which is controlled by multiple signaling pathways, as mentioned earlier.…”

“…The activation of these pathways leads to changes in CDH1 expression, reducing its level and altering cell-to-cell adhesion junctions, ultimately allowing cells to invade and migrate. During the reduction of CDH1 quantity, proteolysis of CDH1 by A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and presenilin-1 (PSEN1) lead to the formation of soluble forms of CDH1 that circulate in the blood plasma [46,49]. This phenomenon could be used to differentiate a normal invasive placenta from an abnormal invasive placenta, as proteolysis is aberrant in the latter.…”

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer

“…MiR-7 plays a role in trophoblasts' invasion via the TGF-β-Smad pathway [ 58 ]. MiR-92a-3p plays a role in endometriosis [ 59 ] and is associated with endometrial receptivity [ 60 ] and trophoblast invasion [ 61 ].…”

Potential Serum Biomarkers in Prenatal Diagnosis of Placenta Accreta Spectrum

“…It is believed that miRNAs may predict PAS. Recently, scientists have also proven that some microRNAs, such as miR-17-5p, miR-21-5p, miR-25-3p, miR-92a-3p, and miR-320a-3, are associated with severity of PAS ( 23 ). Researchers also found that miRNA can predict PAS prognosis.…”