Male infertility is an increasingly serious global health problem. As an organ with immune privilege, the testis possesses a unique immune microenvironment that shapes normal spermatogenesis. Distinct from the testicular microenvironment, the epididymis plays a critical role in both sperm maturation and immune regulation. This review aims to systematically describe the regulatory mechanisms of the testicular and epididymal immune microenvironment and, using various diseases as examples (varicocele, testicular torsion, prostatitis, orchitis, viral infections, environmental toxicant exposure, aging and obesity), to explore in depth how disruption of this balance leads to male infertility through immunological pathways. Targeted antioxidant and anti-inflammatory interventions on specific immune pathways currently represent major therapeutic directions. Although many precision interventions and other emerging therapies remain at the experimental stage, they provide broad prospects for the development of novel treatment paradigms.
Liu et al. (2026) studied this question.