Sex-comparative analysis of the miRNome of human amniotic stem cells during obesity

Experimental evidence indicates differences between women and men in several medical areas, including susceptibility to metabolic diseases. Sexual dimorphism could be influenced by microRNA (miRNA)-mediated regulation of gene expression, and miRNAs have also been implicated in fetal programming of obesity. Our previous finding of altered proteome in human amniotic stem cells (hA-MSCs) during obesity (Ob-) prompted us to look for gender-related differences in the miRNA regulation of gene expression in Ob-hA-MSCs that might be involved in metabolic changes. Using small RNA-sequencing we studied the miRNomes of 7 Control (Co-) hA-MSCs and 13 Ob-hA-MSCs from mothers of boys (3 M-Co, 6 M-Ob-) or girls (4 F-Co-, 7 F-Ob-). Most miRNAs were similarly expressed in the Co-hA-MSCs regardless of offspring gender, whereas 13 miRNAs were down-expressed and miR-146a was up-expressed in F-Ob-hA-MSCs vs M-Ob-hA-MSCs (p<0.05). Analysis of the gene targets of gender-deregulated miRNAs predicted impairment of various mechanisms (inflammatory and immune responses, transcriptional and post-transcriptional RNA machinery, and macromolecule metabolism and organization, cell cycle). In conclusion, although the post-partum implications of the gender-related miRNA differences identified in Ob-hA-MSCs are obscure, we provide the first demonstration that the obesogenic environment could affect the fetal hA-MSC epigenetics in a gender-specific fashion.