Mucuna pruriens mitigates aging-related testicular dysfunction and sperm parameters by restoring cell adhesion molecules and junctional complexes.

Aging is associated with progressive testicular dysfunction, including disruption of the blood-testis barrier (BTB), loss of junctional proteins, impaired spermatogenesis, and reduced fertility. This study examined the therapeutic effects of Mucuna pruriens (M. pruriens), a leguminous plant with potent antioxidant and anti-inflammatory properties, on age-related degeneration of testicular junctional molecules in male Wistar albino rats. Adult (4-5 months) and aged (20-22 months) rats were divided into M. pruriens-treated and untreated groups, with 6 animals in each group. The treatment groups received a dose of M. pruriens seed extract (gavage) of 200 mg/Kg body weight for an experimental period of 45 d. Testicular tissues were analyzed via histology, Western blotting, and immunofluorescence to assess BTB protein expression, while epididymal sperm were evaluated for count, motility, viability, and membrane integrity. Results showed that aging causes a significant decrease in BTB proteins, including claudin-1, E-cadherin, N-cadherin, β-catenin, and zonula occludens-1 (ZO-1), along with disrupted seminiferous tubules, thinning of the epithelium, increased interstitial spaces, Sertoli cell vacuolization, and germ cell loss. However, M. pruriens-treated rats showed increased expression of the mentioned BTB proteins. In treated aged rats, the anti-inflammatory cytokine TGF-β emerged as a senescence marker, whereas IL-10 levels mirrored those of IL-6. Pro-inflammatory markers TNFα and IL-1β decreased in the M. pruriens-treated groups. At the same time, MIF, AR and ERα expression increased in the aged rats treated with M. pruriens, indicating recovery of the testicular microenvironment. Functionally, aged rats experienced notable reductions in sperm count, viability, motility, and membrane integrity. Conversely, M. pruriens-treated aged rats displayed a marked restoration of BTB protein levels and proper localization at Sertoli-Sertoli and Sertoli-germ cell junctions. Histological analysis showed improved seminiferous structures, fewer interstitial gaps, a thicker germinal epithelium, and increased spermatozoa. M. pruriens treatment significantly enhanced sperm parameters in aged rat testes. These findings demonstrate that M. pruriens supplementation can reduce age-related testicular degeneration by restoring junctional protein expression, maintaining BTB integrity, and supporting spermatogenesis.