The Expression Pattern of MicroRNAs and the Associated Pathways Involved in the Development of Porcine Placental Folds That Contribute to the Expansion of the Exchange Surface Area.

The development of the microscopically folded structure of the diffuse epitheliochorial placenta in pigs is important because it expands the surface area for maternal-fetal exchange, resulting in an increase in placental efficiency. To better understand the regulatory mechanisms involved in this process, we characterized miRNA expression profiles in porcine placentas during the initiation and establishment of placental fold development. A total of 42 miRNAs were found to be differentially expressed, and their putative target genes were predicted using four target prediction programs. Following a comparative analysis with published gene expression pattern data obtained from porcine placentas in the corresponding stages of placental fold development, only those genes that were negatively correlated with miRNA expression were retained for further function and pathway enrichment analysis. The results showed that the up-regulated miRNAs were associated mainly with extracellular matrix remodeling and tissue morphogenesis, while the down-regulated miRNAs were related to cell proliferation and signal transduction. Furthermore, we provide evidence that miR-130b may facilitate the expression of HPSE, which has been reported to be a regulator of the folding of the pig placenta, by suppressing the expression of PPARG. In addition, we also reveal that the miRNA-target pairs expressed in the pig placenta may trigger the degradation of the stromal matrix and basement membrane (miR-29a-COL1A2, COL3A1, and LAMC1) and regulate trophoblast epithelial cell adherens junctions (the miR-200 family and miR-205-ZEB2-CDH1) and proliferation (miR-17-92 cluster-HBP1 and ULK1). Taken together, these results indicate that miRNAs and related pathways may have potential roles in porcine placental fold development.