title: Methylphenidate has dose-dependent negative effects on rat spermatogenesis: decreased round spermatids and testicular weight and increased p53 expression and apoptosis.
abstract: In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental groups of 14 rats each. For 90 days, each group via gavage received the following: group 1 = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-β1 and p53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction of round spermatids in stage II. Group 3 had reduction in both stage II and stage V spermatids, as well as lower testicular weight. The p53 expression was increased in group 3. In groups 2 and 3, the TGF-β1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round spermatids but also by increasing apoptotic death and p53 activation. The findings of the study, however, must be cautiously interpreted.
authors.affiliation: Department of Pediatric Neurology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Cansu
authors.forename: Ozgür
authors.initials: O
authors.lastname: Ekinci
authors.forename: Ozalp
authors.initials: O
authors.lastname: Ekinci
authors.forename: Ayse
authors.initials: A
authors.lastname: Serdaroglu
authors.forename: Deniz
authors.initials: D
authors.lastname: Erdogan
authors.forename: Zafer Kutay
authors.initials: ZK
authors.lastname: Coskun
authors.forename: Seren Gulsen
authors.initials: SG
authors.lastname: Gürgen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D008297:Male; D008774:Methylphenidate / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D008774:Methylphenidate