Placental mesenchymal stem cell-derived exosomes treat endometrial injury in a rat model of intrauterine adhesions.

Intrauterine adhesion (IUA) refer to persistent inflammation and fibrosis due to damaged or infected endometrium and eventually lead to dysfunction. This study aimed to explore the therapeutic effects of exosomes (Exos) derived from placental mesenchymal stem cells (PMSCs) on endometrial repair in a rat model of IUA and to elucidate the underlying molecular mechanisms. PMSCs were characterized using flow cytometry and differentiation assays (osteogenic, adipogenic, and chondrogenic). Exos were isolated via ultracentrifugation and validated through transmission electron microscopy, nanoparticle tracking analysis and Western blot. An IUA model was established via electrocoagulation, and endometrial repair was assessed using hematoxylin-eosin (HE) and Masson staining. RNA sequencing, differential expression analysis and protein-protein interaction (PPI) network construction were employed to investigate the molecular mechanisms of PMSC Exos mediated repair. The role of miR-143 in targeting MyD88 and modulating the NF-κB signaling pathway was confirmed using Dual-Luciferase Reporter Assay and qRT-PCR. PMSC Exos significantly improved endometrial thickness, increased glandular number and reduced fibrosis in the IUA model. RNA sequencing and differential expression analysis screened 3980 differentially expressed genes (DEGs) common to the IUA vs normal groups and Exo vs IUA groups. Enrichment analysis revealed significant involvement of immune system processes, natural killer cell-mediated cytotoxicity and NF-κB signaling. PMSC Exos delivered miR-143, which targeted MyD88, thereby regulating the NF-κB pathway. PMSC Exos effectively repaired endometrial damage in the IUA model by modulating the NF-κB signaling pathway through miR-143 delivery. These findings suggest that PMSC Exos hold promise as a novel therapeutic strategy for IUA, offering insights into the molecular mechanisms underlying endometrial repair.