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Endocrine Abstracts (2019) 65 OC6.3 | DOI: 10.1530/endoabs.65.OC6.3

SFEBES2019 ORAL COMMUNICATIONS Reproductive Endocrinology and Biology (6 abstracts)

Investigating the impact of altered maternal extracellular vesicle miRNAs on placental function in women with gestational diabetes complicated by large for gestational age infants

Kate Timms 1 , Sarah J Cartland 1 , Panagiotis Ntostis 1 , Ponnusamy Saravanan 2 , Nigel Simpson 1 , Eleanor Scott 1 & Karen Forbes 1

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

Gestational diabetes mellitus (GDM) increases fetal morbidity/mortality, and is associated with elevated risks of offspring cardiometabolic disease. These risks are compounded in infants born large for gestational age (LGA) rather than appropriate size (AGA), a common complication of GDM associated with altered placental function. Circulating extracellular vesicle (EV)-associated miRNAs are internalised into the placenta and are emerging as key GDM mediators, with their role in LGA yet to be explored. We hypothesise that maternal EV-miRNAs may alter placental function in concurrent GDM-LGA. Serum was collected from GDM women (26–28 weeks). Birth outcomes and placental tissue were collected at delivery. EV-associated miRNAs were profiled using qPCR arrays (n=7) which showed that miR-200c-3p (2.78-fold; P<0.05 vs. AGA) and miR-375 (4.74-fold; P<0.01 vs. AGA) were elevated in the sera of GDM women with LGA infants and in the placentas of a separate cohort (P<0.05 vs. AGA; qPCR). Gene ontology enrichment analysis identified that predicted targets (e.g. insulin-like growth factor receptor-1 (IGF1R), a key regulator of placental proliferation) of these miRNAs are central to placental metabolism/development. To functionally confirm these predictions, miR-200c-3p and miR-375 were overexpressed in the placental BeWo cell-line (miR-200c-3p 8000-fold, P<0.05; miR-375 13-fold, P<0.05; n=4) or normal human term placental explants (miR-200c-3p 9-fold, P<0.05; miR-375 30-fold, P<0.05; n=3) by transfecting with specific miRNA-mimics or non-targeting control (NT; 100 nM; 73 h). The percentage of proliferative Ki67+ve BeWo cells (fluorescence immunocytochemistry) was reduced by miR-200c (−17%; P<0.01 vs. NT) and miR-375 (−19%; P<0.05 vs. NT) transfection (n=10). Preliminary Western blot data indicates a trend towards decreased IGF1R in placental explants overexpressing miR-375 (56% reduction vs. NT; n=3). These data demonstrate that miR-200c-3p and miR-375 – miRNAs elevated with concurrent GDM and LGA in maternal serum/placenta with concurrent GDM-LGA – alter placental proliferation, potentially linking maternal serum components to fetal growth in GDM.

Volume 65

Society for Endocrinology BES 2019

Brighton, United Kingdom
11 Nov 2019 - 13 Nov 2019

Society for Endocrinology 

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