ESPE Abstracts (2015) 84 FC10.2

The Altered Circulating miRNA Profile in Maternal Obesity Associate with Pre- and Post-Natal Growth

Judit Bassolsa, Gemma Carreras-Badosaa, Alexandra Bonmatíb, Francisco-Jose Ortegaa, Josep-Maria Mercaderc, Anna Prats-Puiga,d, Josefa Sanchezb, 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: Gestational obesity has not only adverse effects on the mothers’ health but also on the developing fetus. Newborns of obese pregnant women have increased birth weight and increased risk for obesity and associated diseases in adulthood. The mechanisms by which maternal nutrition induce these changes in the offspring may involve microRNAs (miRNAs) regulation.

Aims and objectives: To study the associations between circulating miRNAs altered in obese pregnant women and pre- and postnatal growth-related parameters.

Methods: Thirteen circulating miRNAs differentially expressed in maternal obesity were quantified in second trimester plasma samples of 42 pregnant women (20 with normal weight and 22 with pre-pregnancy obesity and/or gestational obesity, as defined by international references)). Patients with preeclampsia, gestational diabetes or with pathologies other than obesity were excluded. Placentas and newborns were weighed at delivery and the latter also at 1, 4 and 6 months of life.

Results: Decreased levels of miR-340 and miR-652 associated with higher placental weight; and decreased levels of miR-423-5p and miR-652 associated with higher birthweight (all P<0.05 to P<0.001). On infants’ follow-up, decreased levels of miR-128a associated with increased weight at 1, 4 and 6 months, and decreased levels of miR-29c and miR-221 associated with increased weight at 6 months. In multivariate analysis, miR-128a (β=−0.474, −=0.001; R2=19.1), miR-29c (β=−0.379, P=0.01; R2=14.3) and miR-221 (β=−0.377, P=0.01; R2=12.14) were predictors of infant’s weight at 6 months, independently of maternal obesity. Insulin/IGF signalling and chemokine signalling pathways were predicted targets of these miRNAs.

Conclusions: We report new data on the potential role of miRNAs as modulators of pre- and post-natal growth. Interventions on these miRNAs might modulate the deleterious effect of maternal obesity in the 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).