hsa_circ_0004121 and hsa_circ_0030162 Differentially Expressed in Plasma of Patients with Recurrent Implantation Failure

Abstract

Background: Recurrent or repeated implantation failure (RIF) is a significant challenge that hampers the success rate of assisted reproductive technology (ART) in achieving pregnancy. The underlying mechanisms of RIF remain unclear. Recent studies have identified distinct expression patterns of circular RNAs (circRNAs) in the endometrial tissues of individuals with RIF. The objective of this research is to evaluate the expression of six candidate circRNAs in the plasma of RIF patients.

Methods: The study included a total of sixty participants, comprising 30 RIF patients and 30 age-matched controls. Specific primers were designed for six circRNAs (hsa_circ_0001713, hsa_circ_0004121, hsa_circ_0030162, hsa_circ_0034642, hsa_circ_0034762, and hsa_circ_0092337), and expression analysis was carried out by RT-qPCR. Blood samples were collected from individuals during the implantation window, and cell-free RNA was extracted from plasma. Statistical analysis was performed using Graphpad Prism software.

Results: Control and RIF groups had mean ages of 34.68 ± 6.2 and 36.80 ± 3.8 years, respectively. Plasma from RIF patients showed significant downregulation of hsa_circ_0030162 (p=0.02) and upregulation of hsa_circ_0004121 (p=0.003) compared to controls. Bioinformatic analysis predicted hsa-miR-125a-3p and hsa-miR-125a-5p as potential targets of hsa_circ_0030162 and hsa_circ_0004121, respectively.

Conclusions: This study demonstrates the differential plasma expression of hsa_circ_0030162 and hsa_circ_0004121 in RIF patients, consistent their expression in endometrial tissue. These circRNAs may contribute to RIF pathogenesis. Further research is needed to validate these findings and explore their clinical utility.

Keywords: Circular RNA; Plasma; Pregnancy; Recurrent implantation failure.

Fig. 1

Expression level of hsa_circ_0034642 and hsa_circ_0034762 in RIF samples. Expression of hsa_circ_0034762 (A) and hsa_circ_0034642(B) in RIF plasma samples in comparison to controls sample showed slightly elevated expression that did not significant. ns: not significant.

Fig. 2

Expression of hsa_circ_0030162 and hsa_circ_0004121 in RIF samples. Expression of hsa_circ_0030162 (A) and hsa_circ_0004121 (B) in RIF plasma samples in comparison to controls samples significantly dysregulated. *: <0.05, **: <0.005.

Fig. 3

CircRNA–miRNA–mRNA regulatory network, which consists of hsa_circ_0030162 and hsa_circ_0004121, two predicted target microRNAs, and 11 predicted target genes.