Viral orchitis and male infertility: A comprehensive review of pathogenic mechanisms and outcomes.

Male reproductive tract infections and inflammations are recognized as significant aetiological contributors of infertility. Orchitis and epididymo-orchitis caused by systemic or local infection, as well as non-infectious aetiological causes, are of special concern with respect to their effect on male reproductive function. Male fertility can be affected by various microorganisms especially viruses. Viruses like HIV and mumps can target testicular cells, result in orchitis. This inflammation of the testes can impair fertility and, in some cases, increase the risk of developing testicular cancer. When microbial infections interact with sperm cells, can cause direct negative consequences including decreased motility, reduced sperm count, and causing sperm cell death. These infections may also compromise male fertility through the disruption of spermatogenesis and impairment of reproductive organ function, primarily mediated by infection-induced inflammatory cytokine release. Epidemiological data connects viral orchitis to male infertility and subfertility. Even with the recognition of these correlations, effective therapeutic strategies remain largely inadequate. Current pharmacologic interventions, including antiviral and anti-inflammatory agents, exhibit suboptimal efficacy, underscoring the necessity for novel, targeted approaches. Hence it is clear to develop therapeutic strategies that can effectively address the complex pathophysiology of viral-mediated testicular impairment. Emerging translational approaches, such as testicular organoid models, are offering novel insights into disease progression and facilitating therapeutic interventions. Advances in single-cell sequencing and multi-omics technologies are further enabling precise mapping of virus-host interactions and cellular vulnerability within the testis. This review summarizes viral impacts on testicular function and outlines emerging strategies to guide for future interventions.