Recombinant human granulocyte colony-stimulating factor improves implantation partly by downregulating Hsa_circ_0001550

Embryonic implantation is a crucial developmental phase characterized by intricate molecular crosstalk between the embryo and endometrium, with emerging evidence implicating circular RNAs (circRNAs) as important regulators. This study elucidated the role of hsa_circ_0001550 in impairing embryo adhesion and evaluated recombinant human granulocyte colony-stimulating factor (rhG-CSF) as a therapeutic strategy. Overexpression of hsa_circ_0001550 in an in vitro adhesion model using Ishikawa cells reduced the adhesion capacity of BeWo or JAR spheroids and diminished the murine blastocyst implantation rate. Knocking down hsa_circ_0001550 increased the adhesive ability of BeWo spheroids. Crucially, administration of rhG-CSF downregulated hsa_circ_0001550 expression and upregulated homeobox A10 and leukemia inhibitory factor, thereby restoring the adhesive capacity. In an endometrial injury model, administration of rhG-CSF enhanced epithelial proliferation (as measured by Ki67), suppressed apoptosis (based on the TUNEL assay), and activated mesenchymal-to-epithelial transition pathways, ultimately improving the embryo implantation rate. Collectively, this study reveals that rhG-CSF improves implantation partly by downregulating hsa_circ_0001550. These findings provide new perspectives for understanding implantation mechanisms and developing therapeutic strategies.