Potential role of circulating microRNAs as a biomarker for unexplained recurrent spontaneous abortion

Abstract

Objective: To compare circulating microRNA (miRNA) profiles between unexplained recurrent spontaneous abortion (URSA) and normal early pregnancies (NEP) and to evaluate the potential role of circulating miRNA as a biomarker for URSA.

Design: Laboratory study using human plasma samples.

Setting: Special hospital and research institutes.

Patient(s): From September 2012 to April 2013, samples of plasma were obtained from 27 URSA patients and 28 NEP patients at 6-10 weeks of gestation at the Department of Reproductive Immunology in Family Planning Special Hospital of Guangdong Province.

Intervention(s): Differential miRNA profiling analysis of plasma collected from URSA and NEP patients was performed with the use of microarray.

Main outcome measure(s): The circulating miRNA expression profile was assessed by means of microarray and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Result(s): Twenty-five circulating miRNAs were expressed differentially in URSA compared with NEP. Of these, nine were overexpressed and 16 down-regulated. Six differentially expressed circulating miRNAs were selected to validate the microarray results, and qRT-PCR data confirmed the reliability of the microarray results. Further analysis showed that four circulating miRNAs (miR-320b, miR-146b-5p, miR-221-3p, miR-559) were up-regulated. In URSA, one circulating miRNA (miR-101-3p) was down-regulated in other larger scale samples according to qRT-PCR. Based on target gene analysis, we speculate that these circulating miRNAs regulate URSA by targeting immune, apoptosis, and angiogenic gene functions.

Conclusion(s): Circulating microRNAs may be involved in URSA pathogenesis and provide a promising new diagnostic biomarker for URSA.

Keywords: Circulating microRNA; biomarker; microarray; normal early pregnancy; unexplained recurrent spontaneous abortion.