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

Abstract

BackgroundThis study aimed to explore the potential mechanisms of exercise to prevent pelvic organ prolapse (POP) and search for diagnostic indictors for POP. MethodsWe used two clinical POP datasets with patients’ information (GSE12852 and GSE53868), a dataset consisting of altered microRNA expression in circulating blood after exercise (GSE69717) for bioinformatic analysis and clinical diagnostic analysis, while a series of cellular experiments were conducted for preliminary mechanical validation. ResultsOur 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. ConclusionsOur 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.