The circRNA Landscape in Recurrent Pregnacy Loss (RPL): A Comparison of Four Reproductive Tissues

Recurrent Pregnancy Loss (RPL), also named Recurrent Spontaneous Abortion (RSA), is a common fertility problem that refers to at least two consecutive pregnancy losses and affects 1-2% of couples all over the world. Despite common causes such as genetic abnormalities, uterine anomalies or hormonal and metabolic disorders, there is still a huge challenge in identifying the causes of about 40-60% of RPL patients. Circular RNAs (circRNAs) are endogenous ncRNAs with a unique closed-loop and single-stranded structure. Accumulated evidence indicates the role of circRNAs in embryonic development and implantation, which may help decipher the mechanisms and causes underlying RSA. Four works were selected in the SRA public repository that used RNAseq analysis in control and RPL samples in four tissues: endometrium, chorionic villus tissue, decidua and decidua immune cells. Two programs were selected for circRNA detection: DCC and CIRI2. A total of 1715 candidate circRNAs were detected after filtering the results. In the differential expression analysis, decidual tissue showed the highest percentage of circRNA with differential expression between cases and controls. CircRNAs originating from genes OGA, FNDC3B, RAB11FIP1, SIPA1L2 and GREB1L showed the highest expression in women suffering from pregnancy losses, in decidual tissue or endometrium. In the GO term enrichment analysis, multiple terms related to embryonic development and immunological response were consistently enriched in villus and decidual tissues. Although some differentially expressed circRNAs were shared between tissues, decidua seems the tissue of choice for analyzing the role of circRNAs in RPL.