Histological effect of melatonin and its agonist on testes in light-exposure and pinealectomized rats

Melatonin (MEL), beyond its role as a pineal hormone, supports male reproduction by regulating circadian rhythms and exerting antioxidant and anti-apoptotic actions in the testes. Disruption of pineal function by pinealectomy and/or continuous light exposure is negatively correlated with spermatogenic activity and is linked to testicular degeneration. This study assessed testicular changes in MEL-deficient models and the capacity of MEL and the MEL-receptor agonist ramelteon (RAM) to ameliorate injury. Adult male albino rats underwent continuous light exposure and/or pinealectomy, then were allocated to control, untreated, MEL-treated, or RAM-treated subgroups. Animals in the continuous light model were exposed to constant light for 10 weeks, whereas animals in the pinealectomy model underwent surgical pinealectomy and were maintained for 9 weeks post-operatively. At the end of the experimental periods, animals were sacrificed and testicular tissues were collected for histological and morphometric evaluation. Seminiferous tubule area, diameter, and epithelial thickness were measured. Continuous light and pinealectomy caused marked disruption of germinal epithelium, epithelial cell and nuclear detachment, tubular necrosis, prominent vacuolar degeneration, widened interstitial spaces, and reduced spermatogenic activity, with the combined model showing the most severe damage. Melatonin treatment significantly improved tissue architecture and spermatogenic layering. Ramelteon produced greater recovery, approaching normal tubular organization and spermatogenesis. Morphometry confirmed reductions in tubule area, diameter, and epithelial thickness in melatonin-deficient rats, with improvement after melatonin and a larger improvement after RAM administration. Based on the histological findings of the present study, RAM treatment was associated with an overall improvement in the structural organization of the seminiferous epithelium compared with the untreated experimental groups. This was evidenced by better preservation of seminiferous tubule architecture, reduced epithelial disorganization, and improved morphometric indices. These findings support melatonergic therapies for preserving fertility during environmental circadian disruption in adult males.