Abstract: As a synthetic analog of codeine, tramadol is often prescribed to treat mild to moderate pains. This study was
designed to estimate and compare the histological effect of tramadol on testes of both juvenile and adult male albino mice. A
total number of 40 healthy male albino mice were classified into two main groups as follows: group I (juvenile group, includes
20 mice aged three weeks) subdivided equally into group Ia (control group received isotonic saline) and group Ib (tramadoltreated
group received 40 mg/kg/d tramadol orally for 30 days); group II (adult group, includes 20 mice aged two months)
subdivided equally into group IIa (control group received isotonic saline) and group IIb (tramadol-treated group). Juvenile
and adult tramadol-treated groups showed numerous testicular changes, including blood vessels congestion, widening of
intercellular spaces, vacuolization in interstitial tissues, luminal germ cells exfoliation, and increased expression of caspase-3
that indicated cellular apoptosis. In the ultrastructural examination, spermatogenic cells degenerated with the frequent
appearance of apoptotic cells. Sertoli cells showed vacuolations, large lipid droplets, and disrupted intercellular cell junctions.
These observed testicular changes were markedly observed in the juvenile group. Testicular abnormalities and apoptotic
changes can be caused by tramadol administration. These abnormalities are more common in juvenile mice.