Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during the First-Trimester Screening

Version 1 : Received: 9 December 2023 / Approved: 12 December 2023 / Online: 12 December 2023 (05:46:17 CET)

A peer-reviewed article of this Preprint also exists.

Timofeeva, A.V.; Fedorov, I.S.; Suhova, Y.V.; Tarasova, A.M.; Ezhova, L.S.; Zabelina, T.M.; Vasilchenko, O.N.; Ivanets, T.Y.; Sukhikh, G.T. Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening. Int. J. Mol. Sci. 2024, 25, 871. Timofeeva, A.V.; Fedorov, I.S.; Suhova, Y.V.; Tarasova, A.M.; Ezhova, L.S.; Zabelina, T.M.; Vasilchenko, O.N.; Ivanets, T.Y.; Sukhikh, G.T. Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening. Int. J. Mol. Sci. 2024, 25, 871.

Abstract

Abstract: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, the condition remains undiagnosed before delivery because of the lacking clear evaluation criteria for each of the three grades of PAS. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. While using deep sequencing, miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profile in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or preeclampsia, were obtained. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset preeclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to literature data, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for 1st trimester screening pregnant women, subject to validation on independent test samples.

Keywords

miRNA; NGS; real-time PCR; peripheral blood; placenta; myometrium; placenta accreta spectrum; first-trimester screening

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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