ESPE Abstracts (2015) 84 FC10.3

Circulating miRNA Expression Profile in Pregestational and Gestational Obesity

Judit Bassolsa, Gemma Carreras-Badosaa, Alexandra Bonmatíb, Francisco-Jose Ortegaa, Josep-Maria Mercaderc, Anna Prats-Puiga,d, Neus Sacotb, Francis deZeghere, Lourdes Ibáñezf, Jose-Manuel Fernandez-Reala,b & Abel López-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: miRNAs are valuable circulating biomarkers and therapeutic targets for metabolic diseases. A differential pattern of miRNAs has been described in pregnant women with preeclampsia or gestational diabetes; however, it is unknown whether maternal obesity affects the profile of circulating miRNAs.

Aims and objectives: To define the circulating pattern of miRNAs in pregestational and gestational obesity; and to explore their associations with maternal metabolic parameters.

Methods: TaqMan Low-Density Arrays (TLDAs) were used to profile plasma miRNAs in 18 pregnant women (six with pregestational obesity (PregestOB), six with gestational obesity (GestOB) and six with normal pregnancies (Control)], during the 2nd trimester of gestation. The most relevant miRNAs were validated in 70 pregnant women (20 PregestOB, 25 GestOB and 25 Control). Maternal metabolic parameters including fasting glucose, HbA1c, HOMA-IR, C-peptide and lipids were assessed.

Results: We identified 13 circulating miRNAs differentially expressed in maternal obesity, including decreased levels of miR-29c, miR-99b miR-103, miR-221, miR-340, and increased levels of miR-30a-5p, miR-130a and miR-150 in GestOB; and decreased levels of miR-122, miR-324-3p, miR-375, miR-652 and increased levels of miR-625 in both PregestOB and GestOB (P<0.05 to P<0.0001 vs control). Decreased levels of several of these miRNAs associated with a more adverse maternal metabolic status (more pregnancy weight gain, glucose, HbA1c, HOMA-IR, C-peptide, TG and less HDL) (all P<0.05 to P<0.001). These miRNAs have been heralded as ‘ribo-regulators’ of glucose homeostasis and lipid metabolism.

Conclusions: This study provides the first identification of altered circulating miRNAs in maternal obesity. The next step will be to demonstrate whether interventions on these miRNAs can avoid the adverse effects of gestational obesity in the mother and/or her offspring.

Funding: This study was supported by grants from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (MS12/03239 and PI13/01257), projects co-financed by FEDER (Fondo Europeo de Desarrollo Regional).