Altered expression patterns of circular RNAs between implantation sites and interimplantation sites in early pregnant mice

Abstract

Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have been found to play important roles in regulating gene expression and participate in several biological processes. However, their specific roles in embryo implantation remain unclear. This study aims to investigate the roles of circRNAs in embryo implantation. In the current study, we screened the expression profiles of circRNAs between implantation sites and interimplantation sites in the endometrial tissue of early pregnant mice on Day 5 using microarray assay. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of four dysregulated circRNAs was performed to validate the microarray results. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and circRNA–microRNA (miRNA)–messenger RNA (mRNA) negative correlation network analyses were performed. The microarray results showed 101 upregulated and 75 downregulated circRNAs (fold change [FC] ≥ 1.5 and p value < 0.05) at implantation sites compared with interimplantation sites. Four randomly selected circRNAs were successfully verified by qRT‐PCR. The GO and KEGG analyses revealed some meaningful terms. Moreover, based on circRNAs microarray data and the miRNA and mRNA high‐throughput data previously published by our groups, differently expressed circRNAs, miRNAs, and mRNAs were performed to conjoint analysis. Then circRNA–miRNA–mRNA negative correlation networks were constructed and 21 downregulated circRNAs, 14 upregulated miRNAs, and 79 downregulated mRNAs were involved in the networks. The findings of this study may provide a novel perspective on circRNAs and lay a foundation for future research into the potential roles of circRNAs in embryo implantation.

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…In mice, the day 5 is critical because blastocysts start the implantation process in the endometrium. To better understand a role of circRNAs in such a crucial developmental window, a complete profiling has been carried out in the endometrial tissues of early pregnant mice on day 5, comparing the expression levels of circRNAs between implantation and interimplantation sites [261]. This analysis strongly suggests that circRNAs may be related to endometrial receptivity and-by working as miRNA sponges-they may target several genes involved in embryo implantation.…”

Circular RNAs: Novel potential regulators in embryogenesis, female infertility, and pregnancy‐related diseases

“…The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the hosting genes were strongly associated with cancer pathways and this relationship might be due to the similarity between embryo implantation and tumor invasion. This implies that some tumor genes and signaling pathways might be involved in embryonic implantation (Zhang, Ding, et al, 2019) (Figure 3).…”

“…Through ERCC/RGC‐A80 spike in for normalization, the average copy number of circRNAs increased from zygote to 4‐cell stage and then decreased to the blastocysts, suggesting that the expression of circRNAs was stage‐specific (Dang et al, 2016). Zhang, Ding, et al (2019) found the expression of 101 circRNAs upregulated and 75 circRNAs downregulated at the implantation sites compared with inter‐implantation sites. The circ‐Foxo3, which suppresses the cell cycle (Du et al, 2016), was downregulated at implantation sites where it regulates cell proliferation and embryo implantation.…”

“…Besides, researchers established a circRNA–miRNA–mRNA network involved in embryo implantation. The target genes of circRNAs in this network were associated with protein kinase activity, response to high‐density lipoprotein particle, insulin binding, Rap1, and PI3K‐Akt signaling pathways (Zhang, Ding, et al, 2019). Elsewhere, it was reported that some circRNAs were upregulated during rabbit embryo development and modulated embryo morphogenesis (Kuang et al, 2020).…”

FBXO18/Circrna211/Mir-431/CSF1 Axis Regulates the Establishment of Endometrial Receptivity Though Activating MAPK and CSF1R/PI3K/AKT/Mtor Pathways in Dairy Goats

“…CircRNAs may act as miRNA sponges to regulate the expression of miRNAs, which regulated the expression of target gene indirectly [3]. Although circRNAs have pleiotropic roles in a variety of biological processes including regulation of myoblasts differentiation in bovine [4], embryo implantation in mouse [5], and milk synthesis in goats [6,7], but their contribution to the formation of RE remains largely unclear.…”