160. THE POTENTIAL ROLE OF microRNAs IN THE DEVELOPMENT OF THE HUMAN PLACENTA IN EARLY PREGNANCY

Abstract

Placental functional development is characterised by dynamic and co-ordinated changes in expression of genes that drive invasion, differentiation and growth. These changes may arise in part from altered expression of microRNAs (miRNAs) via their regulatory networks. MiRNAs are short, single-stranded, non-coding RNAs involved in the post-transcriptional repression of gene expression. MiRNAs bind to complementary sites in the 3'UTR of target mRNAs to repress or silence translation. MiRNAs have been detected in the mammalian placenta, but their patterns of expression throughout pregnancy have not been systematically characterized. Using microarrays, miRNA gene expression was compared at two stages (6–8 weeks, 10–12 weeks) in early gestation, in chorionic villi of human placentas (term ~40 weeks). Putative and validated targets of differentially expressed miRNAs were extracted from freely accessible databases, miRBase [1], PicTar [2], TargetScan [3] and miRecords [4]. 15 miRNAs were differentially expressed between these gestational ages (p<0.05). 11 of these miRNAs were upregulated in 10–12 week villi and 4 were downregulated. Many of the differentially expressed miRNAs are members of the same polycistronic clusters, suggesting that these miRNAs may be co-expressed. Shared targets of differentially expressed miRNAs from the same clusters were assessed using Ingenuity Pathways Analysis, to search for significantly represented molecular networks. All downregulated miRNAs at 10–12 weeks shared 35 putative targets and fell into 1 of 2 clusters, on chromosome 13 or X. Previously validated targets include PTEN [5], Notch1 [6], VEGFA [7], CDKN2A [8] and DHFR [9] . Six of the upregulated miRNAs at 10–12 weeks are members of 3 clusters on chromosome 19, 9 and X. Networks targeted by these cluster members include PTEN, HIF1α and IL-12 signalling. Together all of these processes are active and important in early placentation and their predicted targeting by differentially expressed miRNAs is consistent with an important role in placental development.