MicroRNA-518d regulates PPARα protein expression in the placentas of females with gestational diabetes mellitus

The placenta is thought to have a critical role in the pathogenesis of gestational diabetes mellitus (GDM), as GDM-associated complications resolve following delivery. Placenta-specific microRNAs (miRNAs) may contribute to the pathology of the development of GDM. The aim of the present study was to evaluate whether the placenta-specific miR-518d contributes to the development of GDM. It was revealed that miR-518d expression was higher in placentas taken from patients with GDM compared with control placentas, whereas the protein levels of the predicted miR-518d target gene, peroxisome proliferator-activated receptor-alpha (PPAR alpha), were lower in placentas from patients with GDM compared with those from control subjects. It was also demonstrated that PPARa was a direct target of miR-518d with a specific binding site at the seed sequence, which determines target specificity. In the placentas of females with GDM increased levels of miR-518d were negatively correlated with the levels of PPARa protein. As PPAR alpha dysregulation may be related to the development of GDM, it is suggested that upregulation of miR-518d may be associated with the pathogenesis of GDM via an effect on the regulation of PPAR alpha expression.