Endocrine Abstracts (2019) 65 P349 | DOI: 10.1530/endoabs.65.P349

miR-1-3p and miR-133-3p are altered in maternal serum EVs and placenta in pregnancies complicated by gestational diabetes with large-for-gestational age babies

Margeurite Kennedy1, Sarah Cartland1, Ponnusamy Saravanan2, Nigel Simpson1, Eleanor Scott1 & Karen Forbes1

1University of Leeds, Leeds, UK; 2University of Warwick, Warwick, UK

Gestational diabetes (GDM) is a form of diabetes that is first diagnosed during pregnancy, complicating 8–24% of all pregnancies. Despite treatment, substantial numbers of babies are born large for gestational age (LGA), predisposing them to cardio-metabolic disease in adulthood. It is difficult to predict which pregnancies are most at risk. The study aimed to determine if circulating maternal serum small extracellular vesicle (sEV) miRNAs have the potential to predict altered fetal growth in mothers with GDM. Maternal serum samples were collected from women at the time of GDM diagnosis (26–28 weeks); placental tissue was collected at delivery and birth outcomes recorded. Serum sEVs were isolated and characterised through electron microscopy, nanoparticle tracking analysis, and Western blotting for EV enriched proteins TSG101 and HSP70. miRNA QPCR arrays were performed and several miRNAs were altered in sEVs in women that subsequently delivered LGA (n=7) compared to appropriately grown for gestational age (AGA) babies (n=7). This includes reduced miR-145-5p and increased levels of ‘angiomiRs’ miR-1-3p, miR-133a-3p and miR-499a-3p, which are all key regulators of vascular development. GDM is associated with altered placenta vascular development, and our previous studies have shown that sEVs can be transported from the maternal circulation into the placenta where they can influence cellular processes. To determine whether altered sEV miRNAs have the potential to contribute to changes in placental vascularisation, we assessed levels of altered sEV miRNAs in placenta. QPCR analysis revealed that miR-1-3p, miR-133a-3p, miR-145-5p and miR-499a-3p were all present in the placenta at term, and that miR-1-3p and miR-133a-3p were reduced in placenta from GDM pregnancies with LGA (n= 11) compared to AGA (n= 11; P<0.05). In conclusion, angiomiRs could have predictive value for aberrant fetal growth in cases of GDM, and miR-1-3p and miR-133a-3p may also contribute to altered placental vascular development.

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