Abstract: BACKGROUND: MicroRNAs, as important molecules regulating gene expression, play a crucial role in tissue repair. Exosomes, as promising drug carriers, have provided a new strategy for targeted therapy by delivering miRNAs. 
OBJECTIVE: To investigate the therapeutic effect of exosomes from adipose-derived mesenchymal stem cells overexpressing miR-122-5p on intrauterine adhesions in rats.
METHODS: Endometrial tissues were collected from patients with intrauterine adhesions and normal endometrial tissue from healthy individuals. The expression difference of miR-122-5p was detected by qPCR. miR-122-5p was transfected into human adipose-derived mesenchymal stem cells using lentiviral vectors, and exosomes were extracted using the 3D FloTrix viva Exo exosome harvesting system. Thirty-six female SD rats were randomly divided into normal group, model group, exosome group, and miR-122-5p-transfected exosome group. The latter three groups were used to establish a model of intrauterine adhesions using a double injury method of curettage and lipopolysaccharide. On day 7 after surgery, the normal group and the model group received PBS injection via the tail vein, while the exosome group and the miR-122-5p-transfected exosome group received natural exosomes and miR-122-5p-transfected exosomes from human adipose-derived mesenchymal stem cells via the tail vein, respectively. On day 7 of treatment, three rats were randomly selected from each group, and uterine tissues were isolated for hematoxylin-eosin staining, Masson staining, and immunohistochemical detection. The remaining six female rats in each group were caged with male rats at a ratio of 2:1. After two weeks of cohabitation, the implantation sites and numbers of embryos in the rats were observed.
RESULTS AND CONCLUSION: (1) miR-122-5p was lowly expressed in the endometrial tissue of patients with intrauterine adhesion (2) A dual-injury method was used to successfully establish a Sprague-Dawley rat intrauterine adhesion model on day 7 post-surgery. Compared with the normal group, the expression of miR-122-5p in the endometrial tissue of the model group was decreased (P < 0.01). (3) After 7 days of treatment, hematoxylin-eosin staining and Masson staining showed that, compared with the normal group, the endometrial thickness and gland number were significantly reduced, and the fibrotic area was significantly increased in the model group (P < 0.05). Compared with the model group, both the exosome group and the miR-122-5p transfected exosome group significantly increased endometrial thickness and gland number and reduced fibrosis (P < 0.05), and the therapeutic effect of the miR-122-5p transfected exosome group was more significant. (4) The pregnancy rates of the normal group, model group, exosome group, and miR-122-5p transfected exosome group were 100%, 33.3%, 66.7%, and 83.3%, respectively. The number of embryos in the model group was significantly lower than that in the normal group (P < 0.05), while the number of embryos in the miR-122-5p transfected exosome group was higher than that in the model group (P < 0.05). The results indicate that miR-122-5p-transfected human adipose-derived mesenchymal stem cell exosomes effectively improve the fertility of rats with intrauterine adhesions by promoting endometrial regeneration and inhibiting fibrosis.

Key words: intrauterine adhesions, endometrial injury, uterine adhesions, endometrial fibrosis, miR-122-5p, adipose-derived mesenchymal stem cells, exosomes