Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth

Abstract

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women—15 preterm and 16 term—were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

MicroRNA Associations with Preterm Labor—A Systematic Review

“…Ramos et al investigated miRNA expression in small extracellular vesicles (sEV) from peripheral blood, comparing term and preterm pregnancies. The study identified differential expression of miR-612 and other miRNAs associated with cellular senescence in preterm pregnancies, highlighting miRNAs' potential role in preterm labor and premature rupture of membranes [35].…”

Maternal–Infant Factors in Relation to Extracellular Vesicle and Particle miRNA in Prenatal Plasma and in Postpartum Human Milk

“…This is not surprising, as miRNAs in prenatal plasma and miRNAs in postpartum human milk are thought to have different tissue sources, with the placenta being a major source of circulating miRNA during pregnancy and the mammary epithelium being the main source of miRNA in human milk [3][4][5]. Of these shared, ubiquitously expressed EVP miRNAs, several have important roles in immune function or have been implicated in pregnancy complications (e.g., hsa-miR-302d-3p, hsa-miR-320e, hsa-miR-1253, hsa-miR-378e, has-miR-1253) [34][35][36][37]. These common miRNAs may, therefore, serve important regulatory purposes for child development and growth across these two windows.…”

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

“…Elevated serum BEV IgG antibody-based asthma and chronic obstructive pulmonary disease diagnosis have also been tested [137] . Additionally, metagenomic and metabolomic profiling of stool BEVs revealed significantly altered Firmicutes and Proteobacteria as well as amino acids, carboxylic acids, and short-chain to long-chain fatty acids metabolism in colorectal cancer patients [305] . Similarly, human EVs and BEVs found in placental tissues can facilitate the identification of new preeclampsia or preterm birth-associated inflammatory biomarker targets.…”