Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved

Abstract

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

“…The miRNAs showing significantly different expression in exosomes were all up-regulated ( Table 3 ) and the majority of them have already been described in connection with various pregnancy-related disorders. These included hsa-miR-1-3p ( 81 ), hsa-miR-183-5p ( 82 , 83 ), hsa-miR-185-5p ( 84 ), hsa-miR-186-5p ( 85 ), and hsa-miR-20a-5p ( 81 ), and the latter three are also normally expressed at higher levels in the first trimester of healthy pregnancies ( 86 ), although in certain studies where exosomes were not separated they are referred to as plasma-specific miRNAs ( 87 ). Interestingly, hsa-miR-26b-5p showed a tendency for upregulation in PE, but was not found to be differentially expressed in another study ( 88 ), which may be due to the heterogeneous patient population included in that study.…”

Appearance of small extracellular vesicles in the mouse pregnant serum and the localization in placentas

“…This effect is considered to maintain the calcium homeostasis in the myometrium and contribute to avoiding preterm birth. On the other hand, miR-25b-3p is suggested for adverse pregnancy outcomes including hypertensive disorders, fetal growth restriction, and preterm birth [ 17 , 35 , 42 ].…”

“…The miRNAs are one of the small noncoding RNAs that can regulate gene expression by targeting messenger RNAs [ 4 ]. It is suggested that miRNAs in maternal circulation influence the state of metabolism during pregnancy, and the variation of miRNAs is beneficial for finding pregnancy disorders such as preeclampsia and fetal intrauterine growth retardation [ 17 , 18 ]. In addition, miRNAs have a possibility to influence delivery processes [ 21 , 36 ] presented the existence of placenta-derived miRNAs and the possibility of miRNAs in the signaling from the fetal membrane to the uterus, especially in the mechanism of birth induction.…”

Identification of miRNAs Involved in Foetal Growth Restriction Due to Maternal Smoking during Pregnancy

“…Another possible target, in this case for the 3′ end of miRNA-25, found with regards to vascular dysfunction is angiogenic factor 1, which is related to correct blood vessel development [ 25 ].…”