Fibroblast Growth Factor 11 Improves Fertility by Alleviating Intrauterine Adhesionss in Rats Through Inhibition of the Transforming Growth Factor‐β1/Smad Pathway

Intrauterine adhesion (IUA), a common gynecological disorder that severely impairs female reproductive health, can cause irreversible damage to patients' fertility. Notably, among patients undergoing surgical treatment, cases of severe intrauterine adhesion not only exhibit a higher postoperative recurrence rate but also present a more prominent tendency toward recurrent miscarriage. Studies have demonstrated that fibroblast growth factor 11 (FGF11) can promote the repair of vascular dysfunction-related damage. However, its role in IUA remains unclear. Clinical cohort analyses demonstrated that the expression of FGF11 in the serum of IUA patients was significantly upregulated, whereas the expression levels of other FGF11 subfamily members (FGF12, FGF13, and FGF14) exhibited no statistically significant differences, a trend further verified in rat models. Furthermore, FGF11 treatment significantly improved endometrial structure in IUA rats. Fibrosis-related protein levels (α-SMA, Collagen I) were markedly decreased, while angiogenesis-, proliferation-, and uterine function-related protein levels (vWF, VEGF-A, CK19, PCNA, PR, ER) were significantly elevated. Mechanistic studies showed that FGF11 reversed abnormal TGF-β1/Smad pathway activation in IUA models and promoted the expression of epithelial-mesenchymal transition (EMT)-related E-cadherin and N-cadherin. The TGF-β1 activator SRI 011381 attenuated FGF11 efficacy and recapitulated TGF-β1/Smad fibrotic pathway dysregulation. Notably, FGF11 enhanced pregnancy rates in IUA rats. In conclusion, FGF11 ameliorates IUAs and improves reproductive capacity in IUA rats, potentially by inhibiting the TGF-β1/Smad signaling pathway.