Ameliorative Effects of Coenzyme Q10 Against Hypoxia‐Induced and Varicocele‐Associated Spermatogenesis Dysfunction in Rat

ABSTRACT Background Studies show that coenzyme Q10 (CoQ10) has multiple benefits for improving idiopathic male infertility. However, its protective effects against hypoxia‐induced damage to the male reproductive system and varicocoele‐associated spermatogenesis dysfunction need further investigation. Objectives This study aims to evaluate CoQ10's preventive efficacy against testicular damage caused by chronic hypoxia and varicocoele, and to explore the underlying mechanisms. Materials and Methods Chronic hypoxia‐induced and varicocoele male rat models were established. CoQ10 was administered intragastrically. Transcriptome analysis of testicular tissue, along with qRT‐PCR and Western blot, was performed to elucidate mechanism and confirm gene and protein expression changes. Results The study revealed that both chronic hypoxia and varicocoele reduce sperm concentration, motility, vitality, and cause vacuolation of seminiferous tubules. Both conditions also lower reproductive hormone levels, increase oxidative stress, and promote germ cell apoptosis. CoQ10 treatment protected against these testicular changes and improved testosterone levels in rats. Seven differentially expressed genes ( Slc38a5 , Adgrg2 , Gpc1 , Arx , Egr2 , Ebp , Il2rb ) were identified in CoQ10‐treated rats with either condition. Enrichment analysis highlighted inflammation as the main affected process in testes for both conditions. qRT‐PCR and Western blot confirmed that CoQ10 significantly reduced IL1β, Egr2, Il2rb, and caspase‐1 expression at both gene and protein levels. Conclusion These findings suggest that CoQ10 improves chronic hypoxia‐induced and varicocoele‐related spermatogenesis dysfunction by reducing inflammation via the caspase1‐IL1β‐egr2 pathway. The study highlights CoQ10's protective role in male reproduction and its potential for treating male infertility linked to hypoxia and varicocoele.