MXRA7 Alleviates Epididymitis from Exercise-Induced Fatigue by Inhibiting Pyroptosis

AimsTo explore exercise-induced fatigue (EIF)s effects on the male reproductive system and MXRA7s regulatory role herein. MethodsWe recruited EIF volunteers for semen/serum tests, established a mouse EIF model via weight-loaded swimming to assess epididymal segmental injury, and constructed pyroptosis models of PC-1/DC-2 cells. Public database transcriptomic analysis identified MXRA7 expression and enriched pathways in epididymitis; MXRA7s function was verified via its knockdown/overexpression in DC-2 cells. PKC-MXRA7 association was explored by phosphorylation assays and CO-IP, and sperm incubation experiments evaluated MXRA7s effect on sperm function. ResultsEIF impaired human sperm motility, reduced mouse sperm quality and induced epididymitis with segment-specific pyroptosis. MXRA7 expression differed in PC-1/DC-2 cells and correlated with pyroptosis; it was phosphorylated by PKC, inhibited the NF-{kappa}B pathway to alleviate inflammation, and mitigated pyroptosis-induced sperm motility damage. ConclusionEIF induces epididymal epithelial pyroptosis and epididymitis, and MXRA7 exerts a protective effect mainly in caudal epididymal cells by alleviating pyroptosis, thus reducing sperm quality damage.