Bone Marrow Mesenchymal Stem Cell-Originated Exosomes Curb Oxidative Stress and Pyroptosis Triggered by Ovarian Ischemia/Reperfusion via the TXNIP/NLRP3 Inflammasome Pathway

Mesenchymal stem cells (MSCs) and their secreted exosomes (Exos) have attracted much interest for their potential against ischemia/reperfusion injury (IRI). In the present research, we employed rat ovarian ischemia/reperfusion injury (OIRI) model and hypoxia/reoxygenation (H/R) model of primary rat ovarian granulosa cells (RGCs) to investigate whether BMSC-Exos could alleviate OIRI. Our data suggested that administration of BMSCs in rats significantly reduced OIRI-resultant histopathological changes, oxidative stress, inflammation, and pyroptosis. In addition, BMSCs downregulated the expression of proteins related to the TXNIP/NLRP3 inflammasome pathway. Based on in vitro experiments, BMSC-Exos could be internalized by RGCs and curbed oxidative stress and pyroptosis in H/R-injured RGCs. This effect may be due to the regulation of TXNIP/NLRP3 inflammasome pathway. Remarkably, our in vivo data were in concordance with our in vitro results, suggesting that BMSC-Exos suppressed OIRI-induced oxidative stress and pyroptosis via the TXNIP/NLRP3 inflammasome pathway. Overall, these results demonstrate good therapeutic efficacy of BMSC-Exos for treating OIRI, which may provide experimental evidence for the potential clinical benefits of BMSC-Exos for ovarian protection.