Circulating microRNAs overexpressed in macrosomia: an experimental and bioinformatic approach

Abstract

Low birth weight (LBW) and macrosomia have been associated with later-in-life metabolic alterations. The aim of this study was to elucidate whether the expression levels of circulating microRNAs (c-miRNAs) associated with adult metabolic diseases are also dysregulated in newborns with LBW or macrosomia. The expression levels of five microRNAs (miRNAs) associated with metabolic diseases were quantified in dried blood spots of newborns with adequate birth weight, LBW and macrosomia by stem-loop real-time polymerase chain reaction. miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p were significantly overexpressed in newborns with macrosomia and showed no significant change in the LBW group compared to normal weight controls. miR-320a showed no statistical difference among groups. We predicted the putative target genes and pathways of the overexpressed miRNAs with bioinformatic tools. Bioinformatic analyses of overexpressed miRNAs predicted target genes involved in carbohydrate metabolism, participate in FoxO and PI3K/Akt signaling pathways, and are associated with diabetes, obesity, and cardiovascular diseases. The overexpression of circulating miR-29a-5p, miR-126-3p, miR-221-3p, and miR-486-5p may explain the increased risk of obesity and diabetes associated with macrosomia. The use of dried blood spots from newborn screening cards to quantify miRNAs expression levels could be an early and minimally invasive predictive tool for these metabolic alterations.

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

“…Moreover, miR-126 plays a protective role in vascular injury and hypoxia through the target FOXO (forkhead box protein O) and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway [reviewed in Pishavar et al ( 101 )]. In addition, reporting the upregulated expression of miR-126 in dried blood spots of macrosomia, the researchers further demonstrated with biological analysis that high levels of miR-126 were associated with a higher risk of obesity and diabetes associated with macrosomia, with a putative target of FOXO and the PI3K/AKT pathway ( 102 ).…”

“…In contrast, overexpression of PGC1α can mediate fatty acid oxidation, attenuating HFD-induced hepatic steatosis ( 124 ). Interestingly, in clinical studies, Ortiz-Dosal et al ( 102 ) quantified miRNAs associated with metabolic diseases in dried blood spots of newborns with adequate birth weight, low birth weight (LBW) or macrosomia. They determined that miR-29a-5p was also upregulated in macrosomia, which may explain the increased risk of obesity and diabetes associated with macrosomia ( 102 ).…”

“…Interestingly, in clinical studies, Ortiz-Dosal et al ( 102 ) quantified miRNAs associated with metabolic diseases in dried blood spots of newborns with adequate birth weight, low birth weight (LBW) or macrosomia. They determined that miR-29a-5p was also upregulated in macrosomia, which may explain the increased risk of obesity and diabetes associated with macrosomia ( 102 ). Consistent with a previous study, Munetsuna et al found that maternal fructose intake resulted in an increase in miR-29a in the livers of the offspring at 160 days of age, which decreased Igf1 mRNA expression.…”

The challenge of spreading DOHaD concept throughout Latin America

“…Likewise, González-Candia et al 5 reviewed diverse studies from their own and other groups to propose the newborn sheep as a translational animal model to study mechanistic aspects of neonatal pulmonary arterial hypertension at high altitude, a recurrent perinatal concern in Andean countries. Still on perinatal health, Ortiz-Dosal et al 6 assessed the expression of microRNAs, related to adult metabolic outcomes, in dried blood spots from newborns with low or high birth weight, which were compared to normal weighed babies. The authors found out a set of microRNAs targeting carbohydrate metabolism-related genes which were increased in macrosomic but not low birth weighted ones.…”