Endocrine Abstracts

Introduction: Gestational diabetes (GDM) affects 1 in 6 pregnancies globally, increasing babies’ risk of being born large-for-gestational-age (LGA). This can cause birth injuries and predisposes offspring to developing cardio-metabolic disease in adulthood. The cause of LGA in GDM is unclear, however GDM placentas have been shown to display abnormal morphology indicative of vascular network immaturity. MicroRNAs (miRNAs) are known regulators of vascular development, including skeletal muscle specific ‘myomiRs’, which control vascular smooth muscle (VSM) differentiation in other systems. We aimed to determine whether myomiRs may be involved in the development of LGA in GDM pregnancies and to investigate their roles in placental VSM differentiation.

Methods: Placentas were collected at delivery and birth outcomes recorded. Levels of vascular myomiRs were quantified via RTQPCR. Primary placental mesenchymal stromal cells (PMSCs) from uncomplicated pregnancies were isolated by collagenase and dispase digestion. PMSCs were characterised via flow cytometry and immunocytochemistry. Differential potential of PMSC was assessed through their ability to differentiate down adipogenic and osteogenic lineages. Differentiation down the VSM lineage was induced through supplementation of growth media with TGF-β1 on a collagen matrix, myomiRs and MYH11 were measured by RTQPCR.

Results: Two of the four myomiRs tested, miR-1-3p and miR-133a-3p, were significantly decreased in GDM-LGA (n = 15) placentas compared to GDM pregnancies with appropriately-grown-for-gestational-age offspring (n = 12; P < 0.05). Characterisation of MSC markers and differential potential confirmed that the cells isolated were PMSCs (n = 3). When induced to differentiate down the VSM lineage, PMSCs on average showed a 6-fold upregulation of VSM marker MYH11, as well as 15- and 12-fold increases in miR-1-3p and miR-133a-3p, respectively (n = 3; P > 0.05).

Conclusions: Decreased levels of placental miR-1-3p and miR-133a-3p in GDM-LGA may be contributing to placental vascular immaturity since these myomiRs appear to be involved with VSM differentiation, however further experiments with a larger cohort are required to confirm this.