Assistant Professor Tufts Childrens Hospital WESTON, Massachusetts, United States
Background: Obesity affects almost one third of all pregnant people in the US. Infants born to mothers affected by obesity have a higher incidence of neonatal adiposity, which is known to correlate with obesity, diabetes (Type II) and cardiometabolic syndrome later in life. The mechanisms that mediate the effects of maternal obesity on fetal fat accrual remain unknown. The epigenetic machinery, a complex network of molecular systems which include non-coding RNAs, has the capacity of modulating fetal gene expression. We hypothesize that the pre-pregnancy BMI modulates the placental miRNAs networks, potentially impacting neonatal adiposity. Objective: To correlate placental miRNA profiles with neonatal adiposity in lean and obese mothers. Design/Methods: Placentas were collected at the time of scheduled cesarean delivery from lean mothers (L) with pre-gravid BMI < 25 kg/m2 (N=39) and from mothers with obesity (OB) with BMI >30 (N=40). The two groups were further divided according to high neonatal adiposity (HA) vs low adiposity (LA) calculated via skinfolds measurements within 48 hours of birth. Next Generation Sequencing (NGS) was performed on placental RNA from all 79 patients. A Spearman correlation analysis between placental miRNAs and neonatal adiposity in L and OB mothers was performed using an absolute correlation coefficient of 0.3 ρ as cut-off and a p-value < 0.05. Results: Globally, 76 placental miRNAs correlated significantly with neonatal adiposity in L and/or OB mothers. No common adiposity sensitive miRNAs were found. In the OB group, 31 miRNAs were identified with the majority (25/31) correlating positively with neonatal adiposity. Notably, a cluster of 3 miRNAs (miR421, 374B and C), from the Xq13.2 region were detected, a genomic duplication in the same region has been associated with obese phenotype in Prader-Willy patients. In the L group, a total of 42 adipose sensitive miRNAs were identified, 26 of these correlated positively. Four of these miRNAs were part of the C19 miRNA cluster (C19MC). Low levels of C19MC expression have been associated with fetal growth restriction supporting a role for these miRNAs on fetal growth.
Conclusion(s): The correlation analysis between placental miRNAs expression and neonatal adiposity in OB and L mothers did not show common miRNAs between the two groups, suggesting that maternal, BMI-specific, placental miRNAs networks modulate fetal fat accrual impacting neonatal adiposity. Further work is necessary to elucidate the role of these adiposity sensitive miRNAs on placental gene expression and function.
