Adiponectin Ameliorates Intrauterine Adhesion-Related Endometrial Inflammation and Fibrotic Changes by Downregulating the NLRP3/IL-1β/TGF-β1 Axis

INTRODUCTION: Intrauterine Adhesions (IUA), a common gynecological condition often caused by infection or endometrial injury, significantly impact women's reproductive and mental health. Its unclear pathogenesis hinders the development of effective treatments. Adiponectin, a bioactive protein with anti-inflammatory and antifibrotic properties, may offer therapeutic potential. This study investigates adiponectin's effects and mechanisms in IUA to inform new clinical strategies.. METHODS: Endometrial tissues from IUA patients and controls were analyzed via immunohistochemistry to assess NLRP3, IL-1β, TGF-β1, and adiponectin expression. A human IUA cell model was established by stimulating human endometrial stromal cells (HESCs) with TGF-β1 (10 ng/ml, 48 hours). Interventions using the NLRP3 inhibitor MCC950, activator nigericin sodium salt, and adiponectin were applied. Protein and mRNA expression levels of NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 were evaluated via Western blot and RT-qPCR. In vivo, IUA model rats were treated with adiponectin, and uterine morphology, gland count, collagen deposition, and inflammatory/fibrotic markers were analyzed. RESULTS: NLRP3, IL-1β, and TGF-β1 expression were significantly upregulated in IUA patient tissues, while adiponectin was downregulated (P<0.05). In the TGF-β1-induced IUA cell model, NLRP3 inhibition with MCC950 reduced IL-1β and TGF-β1 levels, whereas NLRP3 activation with nigericin increased them. Adiponectin intervention significantly decreased NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 expression in vitro (P<0.05). In IUA rats, adiponectin improved uterine morphology, increased endometrial glands, reduced collagen fiber deposition, and downregulated NLRP3, IL- 1β, and TGF-β1 expression (P<0.05). DISCUSSION: Adiponectin alleviates endometrial inflammation and fibrosis in IUA, potentially by modulating the NLRP3/IL-1β/TGF-β1 signaling pathway. These findings highlight adiponectin's role in mitigating IUA progression and provide a theoretical basis for its clinical applications. CONCLUSION: Adiponectin reduces inflammation and fibrosis in IUA by suppressing the NLRP3/IL-1β/TGF-β1 axis, offering new insights for IUA treatment strategies.