Exploring the mechanism of IL-33-mediated activation of the Wnt/β-catenin signaling pathway through Ror2 in intrauterine adhesions.

BACKGROUND

Intrauterine adhesions (IUA) are a major cause of secondary infertility, yet existing treatments have limited efficacy. This study explores the potential of targeting Ror2, a key mediator in the IL-33/Wnt/β-catenin signaling pathway for IUA treatment.

METHODS

First, we established an IL-33-induced intrauterine adhesion (IUA) mouse endometrial organoid (EMOs) model. Using parallel reaction monitoring (PRM) technology, we identified Ror2 as the target protein linking IL-33 to the Wnt/β-catenin signaling pathway in mouse uterine tissue. Subsequently, we constructed lentiviral vectors for Ror2 knockdown (Lv-shRor2) and overexpression (Lv-Ror2) to evaluate the role of Ror2 in endometrial fibrosis and stem cell proliferation. Finally, we assessed murine fertility via in situ injection of Ror2-overexpressing adenoviral particles (Ad-Ror2) into the uterine cavity.

RESULTS

The results showed that IL-33 at 100 ng/ml for 24 h had the strongest effect on the model. Lv-shRor2 promoted endometrial fibrosis by activating the Wnt/β-catenin pathway, while Lv-Ror2 inhibited this pathway, enhancing endometrial stem cell proliferation and improving fertility in IUA mice.

CONCLUSIONS

These findings suggest that Ror2 could be a promising target for regulating the Wnt/β-catenin pathway in IUA treatment.