Differential Expression of Micro-RNA in Maternal Blood of Pregnancies Affected with Late-Onset Fetal Growth Restriction.

Abstract

Introduction: Micro-RNAs (miRNAs) participate in different biological processes, including fetal hypoxia. In this work, we aimed to evaluate the existence of a miRNA differential expression profile in maternal blood of pregnancies affected with late-onset fetal growth restriction (LO-FGR).

Methods: In a prospective study, a group of 35 fetuses were evaluated with Doppler ultrasound after 36 weeks. These included 15 fetuses with LO-FGR defined as fetal birth weight <10th centile plus a cerebroplacental ratio (CPR) <0.6765 MoM and 20 normal fetuses (normal BW plus a normal CPR). Afterward, for every pregnancy, maternal blood plasma was collected at birth, miRNAs were extracted, and full miRNA sequencing was performed using 20 of the indicated samples (12 with LO-FGR and 8 normal), determining the existence of differentially expressed miRNAs. Finally, this differential expression was validated in a wider population of 35 fetuses by means of quantitative reverse transcription polymerase chain reaction.

Results: Full mRNA sequencing showed that FGR mothers expressed differential expression of several miRNA. The highest differences were seen for miR-486-5p/3p, miR-516a/b-5p, miR-19a/b-3p, miR-296-5p, miR-10b-5p, miR-205-5p, and Let-7g-5p. However, PCR validation only confirmed significant differences in miR-486-5p/3p.

Conclusion: Mothers delivering FGR fetuses express a miRNA profile, which includes differential expression of miR-486-5p/3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose maternal blood miRNAs as a valid tool in the diagnosis and management of FGR.