Exercise-induced circulating exosomes potentially prevent pelvic organ prolapse in clinical practice via inhibition of smooth muscle apoptosis

Background: This study aimed to explore the potential mechanisms of exercise to prevent pelvic organ prolapse (POP) and search for diagnostic indictors for POP.Methods: We used two clinical POP datasets with patients' information (GSE12852 and GSE53868), a dataset consisting of altered microRNA expression in circulating blood after ex-ercise (GSE69717) for bioinformatic analysis and clinical diagnostic analysis, while a series of cellular experiments were conducted for preliminary mechanical validation.Results: Our results show that AXUD1 is highly expressed in the smooth muscle of the ovary and is a key pathogenic gene in POP, while miR-133b is a key molecule in the regulation of POP by exercise-induced serum exosomes. The AUCs of AXUD1 for POP diagnosis were 0.842 and 0.840 in GSE12852 and GSE53868 respectively. At cut-off value = 9.627, the sensitivity and specificity of AXUD1 for predicating POP is 1.000 and 0.833 respectively for GSE53868, while at cut-off value = 3324.640, the sensitivity and specificity of AXUD1 for predicating POP is 0.941 and 0.812 separately for GSE12852. Analysis and experiments confirmed that miR-133b can directly regulate AXUD1. miR-133b mediated C2C12 myoblasts proliferation and inhibited hydrogen peroxide-induced apoptosis.Conclusions: Our study proved that AXUD1 is a good clinical diagnostic indicator for POP and provided a theoretical basis for future prevention of POP through exercise and a potential target for intervention in muscle dysfunction.