Tagliaferri, Salvatore (2021) IDENTIFICATION OF HYPOXIA-REGULATED MICRORNAs IN MATERNAL BLOOD AS EARLY PERIPHERAL BIOMARKERS FOR FETAL GROWTH RESTRICTION. [Tesi di dottorato]

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Abstract

Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction(FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus(FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidate for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p that were upregulated in FGR blood samples before the 32nd week of gestation as compared to aged matched control group. By contrast, miRNA103-3p and miRNA107-3p analyzed between the 32nd and 37th week of gestation showed lower expression in the FGR group compared to aged matched controls. Notably, the expression of all miRNAs was increased through gestation in healthy control group. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic strategies in order to alleviate the burden of this disease.

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