Morphological, histopathological, and immunohistochemical changes in tissues of adult male Sprague-Dawley rats orally treated with isotretinoin

Abstract

Isotretinoin (ISO) is the most effective drug prescribed by dermatologists for the treatment of acne vulgaris and other clinical skin cases. A significant obstacle to using ISO is concerns regarding its adverse effect profile. Despite the well-established reproductive toxicity in females, information on the effects on human male fertility is scarce, contradictory, and inconclusive. This study aimed to investigate the potential histological and histochemical effects of ISO. Isotretinoin was administered orally for seven successive days to Sprague Dawley male rats in a 5-20 mg/kg/day dose range. Standard histological and immunohistochemical techniques were used to evaluate ISO side effects. High doses of ISO led to infiltration of inflammatory cells in hepatic tissues, atrophy of the kidney glomeruli, and collapse of testicular compartments. Decreased E2F4 production was positively correlated to a reduced rate of spermatogenesis. The findings provide further evidence for ISO's cytotoxic and reprotoxic potencies. These effects are probably partly due to slowing down the expression of an E2F4 transcription factor. The dysregulated gene may play an essential role in spermatogenesis. The diagnostic value of the E2F4 gene needs to be further validated by different proteomics approaches, and its precise role in spermatogenesis needs to be investigated.