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

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.

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).

These findings suggest that the miRNA expression may reflect metabolic dysregulation during pregnancy and influence cardiometabolic risk in both women and their offspring.