MicroRNA expression profile in the basal plate of human placenta associates with spontaneous preterm birth

Abstract

Abstract

Introduction: MicroRNAs regulate post-transcriptional gene expression. Their expression has been linked to many pregnancy complications, including preterm birth. Placental microRNA levels differ between preterm and term pregnancies. Not much is known about the targets that are affected by these differences in microRNA expression. We investigated associations between microRNA expression levels in the basal plate of the placenta and their targets and the onset of preterm birth.

Methods: MiRNAomes of spontaneous preterm (n = 6) and term (n = 6) placentas were characterized using RNA sequencing. MicroRNA target and enrichment analyses were performed to explore potential gene targets and pathways. Selected findings were validated using qPCR (n = 41). MicroRNA mimic transfection and luciferase reporter assays were performed to test if certain microRNAs regulate their predicted target, SLIT2, the expression of which has been shown to associate with preterm birth.

Results: We identified 39 differentially expressed microRNAs from the preterm placentas compared to term. Many downregulated microRNAs were from the placenta-specific C14MC microRNA cluster. Target gene and pathway analyses showed that microRNAs that associate with preterm birth target transcription related factors and genes linked with protein binding and invasive pathways. Eight of the identified microRNAs putatively target SLIT2, including miR-766-3p and miR-489-3p. Luciferase reporter assay suggested that these microRNAs regulate SLIT2 expression.

Discussion: MicroRNA expression changes are associated with spontaneous preterm birth. A group of microRNAs targeting the same gene or genes belonging to the same pathway can have a significant effect on the critical processes maintaining pregnancy and placental functions.