High-Throughput Sequencing of Circulating MicroRNAs in Plasma and Serum during Pregnancy Progression.

Elena S Vashukova,Roman A Illarionov,Lada A Ivanova,Mariya G Butenko,Olga V Pachuliia,Natalya O Yurkina,Marina S Zainulina,Olesya N Bespalova,Andrey S Glotov,Polina Y Kozyulina,Dina R Eremeeva,Tatyana B Postnikova

doi:10.3390/life11101055

Abstract

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities.

Highlights

IntroductionMiRNAs negatively regulate gene expression by binding to the 30 -untranslated region of the target mRNAs and may possess important control functions in diverse biological processes, including embryonic development, cellular differentiation, proliferation, and apoptosis [1,2,3]
Perhaps even more important is the study of the miRNAs role in the progression of normal pregnancy, which was the subject of our pilot research
Our results confirmed that miRNA concentrations and profiles in plasma and serum change across the normal pregnancy

Summary

Introduction

MiRNAs negatively regulate gene expression by binding to the 30 -untranslated region of the target mRNAs and may possess important control functions in diverse biological processes, including embryonic development, cellular differentiation, proliferation, and apoptosis [1,2,3]. MiRNAs are shown to be involved in regulation of pregnancy progression [4]. Biomarkers found in biological fluids are useful to study physio-pathological processes and to define actual disease progression [9]. MiRNAs can play an important role as one of these biomarker types. Some circulating miRNAs have already been established as prospective biomarkers of various diseases [12,13,14,15]. The profile of circulating miRNAs in normal pregnancy remains poorly investigated

Objectives

Methods

Discussion

Conclusion