Embryonic miRNA Profiles of Normal and Ectopic Pregnancies

Abstract

Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p) and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223) in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans.

MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy

“…miR-873 was previously shown to be among five miRNAs downregulated in EP in a miRNA microarray comparison of pregnancy derived tissues from patients with EP and those with voluntary termination of pregnancy (VTOP) [24], which is consistent with the results of the present study. However, Dominguez et al showed that miR-223 was upregulated in EP, which differs from our results showing that miR-223 expression was significantly lower in EP than in SA.…”

“…In the study by Dominguez et al the upregulation of miR-223 was further validated by real-time PCR in a larger sample of embryonic tissues from EP and VTOP, and it was further shown to target GALNT1, a gene in the mucin biosynthesis pathway. Nevertheless, the study by Dominguez et al did not compare EP and SA [24]; therefore, whether the results of the two studies are in accordance is difficult to determine. Zhi et al showed that miR-223 was shown to inhibit bladder cancer cell migration and invasion by downregulating its target ZEB1 [25].…”

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

“…MiRNAs are small, non-coding RNAs that can modulate (mainly repress) gene/protein expression, primarily via interaction with seed regions at the 3' untranslated region (3'-UTR) of target genes, thereby promoting mRNA degradation or Kisspeptin and miR-324-3p in Ectopic Pregnancy preventing protein translation (26). Deregulation of miRNA expression in embryonic/ placental tissues and the fallopian tube has been reported in EP (27)(28)(29). These studies have surfaced changes in the expression patterns of miRNAs of the let7 family, as well as mir-132, miR-145, miR149, miR-182, miR-196, miR-223, and miR-424 in ectopic implantation; yet, the putative mechanistic implications for these alterations are yet to be elucidated.…”

Genome-wide identification of novel ovarian-predominant miRNAs: new insights from the medaka (Oryzias latipes)

“…Hsa-miR-487b is more widely expressed in endothelial and muscle cells in humans and mice, including in cancer cells464748. Hsa-miR-1288 is upregulated in ectopic pregnancy patients49 and associated with the progression of colorectal cancer50. Mmu-miR-743a is expressed in mouse brain and testis and has possible roles in oxidative stress and neurodegeneration5152.…”