A Comprehensive Review of the Potential Effects of Ophiocordyceps sinensis and Cordyceps militaris on Spermatogenesis

Spermatogenesis depends on coordinated endocrine regulation, intact seminiferous tubule architecture, oxidative balance, and preservation of the blood–testis barrier (BTB). Disturbance of these processes contributes to impaired sperm production and male infertility. Ophiocordyceps sinensis (syn. Cordyceps sinensis) and Cordyceps militaris are medicinal fungi of growing interest in reproductive biology, while cordycepin, a Cordyceps-derived pure compound, has emerged as a major candidate mediator of these effects. Previous reviews have focused mainly on general pharmacology or Leydig-cell steroidogenesis and have not comprehensively integrated evidence across structural, endocrine, and functional aspects of spermatogenesis. This literature review provides a mechanism-oriented synthesis of the potential effects of O. sinensis, C. militaris, and cordycepin on male reproductive function. Experimental evidence indicates that these agents can improve male reproductive outcomes through multiple convergent mechanisms. At the structural level, they preserve or restore seminiferous tubule architecture, improve Sertoli- and germ-cell organisation, maintain Leydig-cell integrity, and protect BTB function. At the functional level, they enhance Leydig-cell steroidogenesis, support testosterone synthesis, improve sperm count, motility, and kinematic parameters, and may also promote sperm hyperactivation and the acrosome reaction during capacitation. The principal mechanisms implicated include adenosine receptor-dependent cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/steroidogenic acute regulatory protein signalling, sirtuin 1 (SIRT1)/ forkhead box o3a (Foxo3a)-mediated antioxidant defence, suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/Mitogen-Activated Protein Kinase (MAPK) inflammatory pathways, and reduction of apoptosis and oxidative damage. O. sinensis, C. militaris, and cordycepin show multi-target potential to support both the morphology and function of spermatogenesis. However, the evidence remains predominantly preclinical, and clinical translation will require standardised preparations, pharmacokinetic characterisation, long-term safety assessment, and rigorous human trials. Major Findings: O. sinensis, C. militaris, and cordycepin improve male reproductive function through preserving seminiferous tubule architecture, supporting Sertoli cell and Leydig cell integrity, protecting the BTB, enhancing testosterone synthesis, and improving sperm count, motility, and kinematic parameters.