Testicular and Epididymal Histology of Rats Chronically Administered High Doses of Phosphodiesterase-5 Inhibitors and Tramadol

Victor U Nna, Augustine L Udefa, Emmanuel O Ofutet, Eme O Osim


Testicular oxidative stress, endocrine disruption and abnormal spermatogenesis in rats exposed to high doses of
phosphodiesterase-5 inhibitors (PDE5i) and opioids, with poor reversibility following withdrawal of treatment had been
reported. In this study, we examined the histopathological effects of high doses of sildenafil, tadalafil, tramadol and
sildenafil+tramadol on the testes and epididymis of rats. Seventy male rats (180 – 200 g b.w) were assigned to one of five
groups (n = 14), namely; A: control (0.2 mL normal saline), B: sildenafil (1 mg/100g b.w), C: tadalafil (1 mg/100g b.w), D:
tramadol (2 mg/100g b.w) and E: sildenafil+tramadol group (dose as in groups B and D). The drugs were administered orally
for 8 weeks. Seven rats were sacrificed per group while the remaining 7/group continued for 8 weeks without treatment.
Histopathological examination was carried out at the end of both phases. After 8 weeks of treatment, mean Johnsen’s
testicular biopsy score (MJTBS) and Leydig cell count decreased significantly (p<0.001) in all treated groups compared with
the control. The MJTBS and Leydig cell count decreased significantly in tramadol (p<0.05) and sildenafil+tramadol (p<0.01)
groups compared with tadalafil group. After recovery, MJTBS and Leydig cell count were significantly (p<0.05) lower in
all the groups compared with the control. Histology of the testes of rats in groups B – E showed reduced germ cell and
spermatozoa population in the seminiferous tubules after 8 weeks treatment. Additionally, their epididymis showed decreased
spermatozoa density. There was no complete reversibility of histopathological alterations following withdrawal of treatment.
High doses of sildenafil, tadalafil, tramadol or sildenafil+tramadol impact negatively on testicular histology with poor
reversal following withdrawal of treatment.

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