Ethanolic seed extract of Artocarpus heterophyllus ameliorates histomorphological, morphometric and functional alterations in the rat testis induced by sildenafil citrate

Background: One in every ten men is affected by ED regardless of their age. Sildenafil citrate is the first-line drug in the treatment of ED and has been associated with seminiferous tubules and testicular degeneration, translating into decreased spermatogenesis. The study evaluated the effect of ethanolic seed extract of Artocarpus heterophyllus on changes in testicular histology, seminal fluid and serum testosterone levels alone and in ameliorating testicular changes induced by Sildenafil Citrate. Methods: Thirty-six adult male Wistar rats were randomly divided into six groups (n=6) and orally dosed daily with NS, seed extract of AH (500 or 1000 mg/kg), SC (50 mg/kg) or AH+SC (1000 mg/kg + 50 mg/kg or 1000 mg/kg + 100 mg/kg). Testicular histopathological and semen analyses were performed via H&E, PAS and Masson’s trichome staining and microscopy. Differences in sperm parameters, testicular size, seminiferous tubule characteristics, Leydig cell volume, and serum testosterone levels were determined. Results: SC administration significantly decreased the sperm count (3.47±1.46), motility (23.414±6.63) and morphology (0.038±0.02) compared to the negative control (6.04±0.47, 27.888±0.81 and 0.058±0.02, respectively). The administration of AH 1000 to SC-positive rats improved these parameters in an SC dose-dependent manner, i.e., 10.54±1.48, 31.516±0.99 and 0.0781±0.02 and 9.36±0.36, 27.314±1.45 and 0.049±0.03 for 50 mg/kg and 100 mg/kg SC, respectively. AH improved the diameter of the seminiferous tubules but decreased the height in SC-positive rats [(297.2±21.64) and (289.0±8.60)] and [100.2±5.03 and 96.8±4.20] compared with SC alone (194.0±51.05 and 60.0±15.26, respectively). SC decreased the Leydig cell diameter (6696.05±2525.53), AH 1000 significantly reversed this (8218.53±1291.49) to above those of the negative control (7584.18±816.46). Serum testosterone levels were lower in the SC group (2.53±1.88) than in the normal group (3.28±1.74), but these levels were improved by AH (4.596±0.73 and 5.46±2.55). Histological examination of the testes revealed increased spermatogenesis and Leydig cell proliferation with a higher dose of extract. Conclusion: This study revealed that the ethanolic seed extract of A. heterophyllus affects male rat reproductive system function by improving sperm parameters, testicular volume, seminiferous tubule characteristics, Leydig cell volume and serum testosterone levels. AH also improved all these parameters in SC-positive rats in an SC dose-dependent manner.