Circulating microRNAs overexpressed in macrosomia: an experimental and bioinformatic approach

J Dev Orig Health Dis. 2020 Oct;11(5):464-472. doi: 10.1017/S2040174420000422. Epub 2020 May 26.

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.

Keywords: Newborn screening cards; birth weight; circulating miRNAs; macrosomia; obesity.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / metabolism*
  • Computational Biology
  • Dried Blood Spot Testing
  • Feasibility Studies
  • Female
  • Fetal Macrosomia / blood
  • Fetal Macrosomia / diagnosis*
  • Fetal Macrosomia / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Humans
  • Infant, Low Birth Weight / blood
  • Infant, Newborn
  • Male
  • Metabolic Diseases / epidemiology*
  • Metabolic Diseases / etiology
  • Metabolic Diseases / genetics
  • Metabolic Diseases / prevention & control
  • Neonatal Screening / methods
  • Pregnancy
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / prevention & control
  • Risk Assessment / methods

Substances

  • Circulating MicroRNA