MXRA7 Alleviates Epididymitis from Exercise-Induced Fatigue by Inhibiting Pyroptosis

Aims To explore exercise-induced fatigue (EIF)’s effects on the male reproductive system and MXRA7’s regulatory role herein.

We 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; MXRA7’s function was verified via its knockdown/overexpression in DC-2 cells. PKCα-MXRA7 association was explored by phosphorylation assays and CO-IP, and sperm incubation experiments evaluated MXRA7’s effect on sperm function.

EIF 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 PKCα, inhibited the NF-κB pathway to alleviate inflammation, and mitigated pyroptosis-induced sperm motility damage.

EIF 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. Competing Interest Statement The authors have declared no competing interest.