Embryonic miRNA profiles of normal and ectopic pregnancies.

Francisco Dominguez,Antonio Pellicer,Juan Manuel Moreno-Moya,Ainhoa Romero,Carlos Simón,Marta Gurrea,Teresa Lozoya,Mercedes Monterde,Sebastian Martínez,Blanca Ferri,Maria Jose Núñez,Rossella Rota

doi:10.1371/journal.pone.0102185

Francisco Dominguez, Antonio Pellicer + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0102185

Copy DOI

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.

Highlights

Ectopic pregnancy (EP) is an early pregnancy complication in which a fertilized ovum implants outside the uterine cavity
Among the 866 miRNAs screened in our microarray, the expression of seven of them were significantly different miRNA in Ectopic Pregnancies between pregnancy-derived tissue obtained from EPs and voluntary termination of pregnancy (VTOP) after applying significance analysis of microarrays (SAM) with an false discovery rate (FDR) correction of less than 5% (Figure 1A)
The miRNA downregulated by the highest amount was hsa-miR-196b, with a 5.94-fold change compared to VTOP tissue, and the miRNA with the most increased expression was hsa-miR-223 with a 9.56-fold change compared to VTOP controls

Summary

Introduction

Ectopic pregnancy (EP) is an early pregnancy complication in which a fertilized ovum implants outside the uterine cavity. The etiology of EP is not completely known, but it is probably due to retention of the embryo caused when the embryo-tubal environment is impaired, allowing tubal implantation to occur [1,2]. EP affects approximately 1–2% of pregnant women, and may seriously compromise women’s health and their future fertility as tubal rupture is a common complication [3]. Recent evidence has conclusively demonstrated that the regulation of numerous key biological processes does not depend only on classical transcriptional mechanisms, and that other regulatory phenomena such as epigenetic mechanisms do have important roles. These epigenetic mechanisms include DNA methylation and the post-translational modification of histones, and small non-coding RNAs, including microRNAs (miRNAs) [6,7]

Objectives

Results

Conclusion