Early-Pregnancy Serum Maternal and Placenta-Derived Exosomes miRNAs Vary Based on Pancreatic ß-Cell Function in GDM.

ABSTRACT

CONTEXT Pancreatic ß-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro-RNAs (miRNAs) with GDM development. To date, no studies have been reported that evaluate the profile of miRNAs present in maternal and placental exosomes in the early stages of gestation from pregnancies that develop GDM. OBJECTIVE: We assessed whether early-pregnancy serum maternal and placenta-derived exosomes miRNA profiles vary according to pancreatic ß-cell function in women who will develop GDM. METHODS: A prospective nested case-control study was used to identify exosomal miRNAs that vary in early-pregnancy stages (<18 weeks of gestation) from women with normoglycemia and those who developed GDM based on their pancreatic ß-cell function using the homeostasis model assessment of pancreatic ß-cell function (HOMA-%ß) index. Early-pregnancy serum maternal and placenta-derived exosomes were isolated to obtain miRNA profiles. Potential target and pathway analyses were performed to identify molecular and metabolic pathways associated with the exosomal miRNAs identified. RESULTS: In early-pregnancy stages, serum maternal exosome size and concentration are modified in GDM group and fluctuate according to HOMA-%ß index. Serum maternal exosomal hsa-miR-149-3p and hsa-miR-455-3p in GDM are related to insulin secretion and signaling, lipolysis, and adipocytokine signaling. Early-pregnancy serum placenta-derived exosomes hsa-miR-3665 and hsa-miR-6727-5p in GDM are related to regulating genes involved in response to immunological tolerance of pregnancy and pathways associated with placental dysfunction. CONCLUSION: Early serum exosomal miRNAs differ depending on their origin (maternal or placental) and pancreatic ß-cell function. This research provides insights into the interactions between maternal and placental exosomal miRNAs and may have implications for identifying potential biomarkers or therapeutic targets for GDM.