Integrating Analysis to Identify Differential circRNAs Involved in Goat Endometrial Receptivity

Abstract

Endometrial receptivity is one of the main factors underlying a successful pregnancy, with reports substantiating the fact that suboptimal endometrial receptivity accounts for two-thirds of early implantation event failures. The association between circRNAs and endometrial receptivity in the goat remains unclear. This study aims to identify potential circRNAs and regulatory mechanisms related to goat endometrial receptivity. Therefore, the endometrial samples on day 16 of pregnancy and day 16 of the estrous cycle were analyzed using high-throughput RNA-seq and bioinformatics. The results show that 4666 circRNAs were identified, including 7 downregulated and 11 upregulated differentially expressed circRNAs (DE-circRNAs). Back-splicing and RNase R resistance verified the identified circRNAs. We predicted the competing endogenous RNA (ceRNA) regulatory mechanism and potential target genes of DE-circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these predicted target genes suggest that DE-circRNAs were significantly involved in establishing endometrial receptivity. Furthermore, Sanger sequencing, qPCR, correlation analysis and Fluorescence in Situ Hybridization (FISH) show that circ_MYRF derived from the host gene myelin regulatory factor (MYRF) might regulate the expression of interferon stimulating gene 15 (ISG15), thereby promoting the formation of endometrial receptivity. These novel findings may contribute to a better understanding of the molecular mechanisms regulating endometrial receptivity and promoting the maternal recognition of pregnancy (MRP).