Placental microRNAs as molecular links between maternal metabolic health and neonatal outcomes

Background and aims: Gestational diabetes (GDM) predisposes women and their offspring to future cardiometabolic disease. Dysregulation of microRNAs (miRNAs) has been linked to environmental influences and complex diseases. MiRNAs (namely miR-27a-3p, -222-3p, -423-3p and -16-5p) and lipoprotein lipase (LPL) are involved in insulin-signaling, glucose and lipid metabolism. Nevertheless, the role of the placental miRNAs in metabolic adaptation in pregnancy remains poorly understood. This cross-sectional study aimed to evaluate the association between placental selected miRNAs expression and clinical parameters of pregnant women and newborns. Methods and results: MiRNAs expression on maternal and fetal side of placenta tissues was analyzed in GDM (n = 25) and normoglycemic (NGT) women (n = 24). Correlations between these miRNAs and placental LPL expression were examined. MiR-27a rs895819 was genotyped. No significant differences in miRNAs expression between GDM and NGT were detected. On the maternal side, placental miR-423-3p expression was negatively associated with total cholesterol (p = 0.037) and triglycerides (TGs) (p = 0.043) at the third trimester. On the fetal side, miR-423-3p was inversely correlated with 2-h OGTT glucose level in GDM (p = 0.029). MiR-222-3p and miR-16-5p expression correlated with HDL-c (p = 0.017 and p = 0.030, respectively). Regarding neonatal outcomes, an association between miR-222-3p on maternal side with birth weight (p = 0.009) and length (p = 0.007) was found. MiR-27a rs895819 TT carriers exhibited higher 2-h OGTT glucose levels compared with other genotypes. In GDM, LPL expression was associated with miR-16-5p (p = 0.014) and TGs (p = 0.036). Conclusions: These findings suggest that the miRNA expression may reflect metabolic dysregulation during pregnancy and influence cardiometabolic risk in both women and their offspring.