MicroRNA expression profiles and networks in placentas complicated with selective intrauterine growth restriction

Abstract

The microRNA (miRNA) profiles of placentas complicated with selective intrauterine growth restriction (sIUGR) are unknown. In the present study, the sIUGR‑associated placental miRNA expression was investigated using microarray and confirmatory reverse transcriptase‑quantitative polymerase chain reaction studies. Placenta samples around the individual insertion region for each umbilical cord were collected from monochorionic twins complicated with (n=17) or without sIUGR (control, n=16). miRNA profile analysis was performed on two sIUGR cases and one control using an Affymetrix microRNA 4.0 Array system. A total of 14 miRNAs were identified to be specifically differentially expressed (7 upregulated and 7 downregulated) among larger twins of sIUGR cases compared with smaller twins of sIUGR cases. The target genes of the identified miRNAs participate in organ size, cell differentiation, cell proliferation and migration. In addition, according to the miRNA‑pathway network analysis, key miRNAs and pathways (transforming growth factor‑β, mitogen‑activated protein kinase and Wnt) were identified to be associated with the pathogenesis of sIUGR. To the best of our knowledge, the results of the current study have provided the most complete miRNA profiles and the most detailed miRNA regulatory networks of placental tissues complicated with sIUGR.

Figure 1.

Venn-analysis of miRNAs. (A) Overlap of L1 vs. S1 and L2 vs. S2. (B) Overlap of (L1 vs. S1, L2 vs. S2) and N1 vs. n1. L1 and L2, placenta tissues supporting larger twins from case 1 and case 2 with sIUGR (intertwin EFW discordance was more than 25%), respectively; S1 and S2, placenta tissues supporting smaller twins from case 1 and case 2 with sIUGR, respectively. N1 and n1, placenta tissues supporting larger and smaller twin form normal MC (intertwin EFW discordance was less than 5%), respectively.

Figure 2.

The 14 DEMs differentiated larger twins (L1 and L2) from smaller twins (S1 and S2). The hierarchical clustering analysis was shown.

Figure 3.

Pathway analysis based on miRNA-targeted genes. (A and B) The histogram of significant pathways targeted by up-regulated (A) and down-regulated miRNA (B) were shown. The vertical axis is the pathway category, and the horizontal axis represents-lg (P-value) of the pathways.

Figure 4.

miRNA-pathway network. Red box nodes and blue box nodes represent up-regulated miRNA and down-regulated miRNA, respectively. Blue cycle nodes represent Pathway. Edges show the inhibitory effect of miRNA on Pathway. Left network included all the pathways. When the area of box or circle is larger, the degree of the miRNA or pathway is bigger. Right network extracted from the left network including the key miRNAs and pathways.

Figure 5.

Expression of (A) has-miR-1, (B) has-miR-370-3p, (C) has-miR-5189-5p, (D) has-miR-373-3p, (E) has-miR-338-5p and (F) has-miR-590-5p in placenta tissues from sIUGR and normal NC by qRT-PCR analysis. n=15.