Abstract

Impaired embryo implantation is a major cause of early gestational failure and represents a significant reproductive challenge. Seminal plasma-derived small extracellular vesicles (SP-sEVs) have been demonstrated as critical regulator in embryo implantation. Circular RNAs (circRNAs) constitute key SP-sEVs cargo that modulate intercellular communication via competitive endogenous RNA (ceRNA) network, providing novel and comprehensive insights into implantation defects. However, the functions and molecular mechanisms of SP-sEVs encapsulated circRNAs in this process remain to be elucidated. This study conducted the first comprehensive characterization of circRNA expression profile in ovine SP-sEVs, identifying 504 distinct circRNAs, with ceRNA network construction and functional enrichment analysis indicating its implantation-related functions. Among these, circSATB1 was the second most abundant and contained the most miRNA targets (21 miRNAs) of the top 10 circRNAs. Subsequent construction of circSATB1-mediated ceRNA network revealed its potential regulatory role in implantation. Following gain- and loss-of-function experiments, circSATB1 was identified to promote endometrial receptivity and embryo implantation by enhancing endometrial epithelial cell (EEC) proliferation, migration, and anti-apoptosis capacities. Mechanistically, circSATB1 exerts its effects by competitively binding miR-200c, thereby alleviating its repression of GATA2 . CircSATB1-regulated endometrial functions may represent potentially therapeutic strategies for addressing impaired embryo implantation.