ESPE Abstracts (2016) 86 RFC10.2

Dysregulation of Placental Mirna in Maternal Obesity is Associated with Pre-and Post-Natal Growth

Judit Bassolsa, Gemma Carreras-Badosaa, Alexandra Bonmatib, Francisco-Jose Ortegaa, Josep-Maria Mercaderc, Anna Prats-Puigd, Francis deZeghere, Lourdes Ibañezf, Jose-Manuel Fernandez-Reala,b & Abel Lopez-Bermejoa,b

aGirona Institute for Biomedical Research, Girona, Spain; bDr.JosepTrueta Hospital, Girona, Spain; cBarcelona Supercomputing Center, Barcelona, Spain; dEUSES University School, Girona, Spain; eUniversity of Leuven, Leuven, Belgium; fHospital Sant Joan de Déu, Barcelona, Spain

Background: Human placenta exhibits a specific miRNA expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders like preeclampsia and intrauterine growth restriction (IUGR), and are potential biomarkers for these pathologies. No studies have been performed in maternal obesity.

Objective and hypotheses: (1) Define the placental miRNA profile in pregnant women with: a) pre-pregnancy (preOB) or gestational obesity (gestOB), b) gestational diabetes (GDM) and c) small for gestational age children (SGA). (2) Explore the associations of circulating miRNAs dysregulated in maternal obesity with pre- and post-natal growth.

Method: TaqMan Low-Density Arrays (TLDAs) were used to profile the placental miRNAs in 30 pregnant women (6 preOB, 6 gestOB 6 GDM, 6 SGA and 6 controls). The miRNAs differentially expressed in maternal obesity were validated in 80 pregnant women (25 preOB, 25 gestOB and 30 control). Placentas and new-borns were weighed at delivery and at 1 month of life.

Results: 9 miRNAs were specific of placentas from women with preOB; 8 miRNAs of placentas from women with gestOB, 8 miRNAs of placentas from GDM women; 13 miRNAs of placentas from women with SGA children, and 386 miRNAs were common in all groups. Among the common miRNAs, 6 miRNAs were decreased in preOB or gestOB (miR-1285, miR-1269, miR-487, miR-214, miR-185 and miR-181) (all P <0.05). In silico analysis showed that these miRNAs were related with cell proliferation and insulin signalling pathway. The miR-1285, miR-1269 and miR-487 were predictors of decreased birth weight independently of maternal obesity (all P<0.010 and R2>15%). Moreover, the miR-1285 was predictor of decreased birth height and increased weight gain in the first month of life (all P<0.008 and R2>10%).

Conclusion: We identified a specific placental miRNA profile in several pregnancy disorders including maternal obesity, GDM and SGA. The dysregulation of placental miRNAs may mediate the growth promoting effects of maternal obesity on the offspring.