Assessment of the In Vivo Reprotoxicity of Isotretinoin in Sprague-Dawley Male Rat

Abstract

Background: Isotretinoin (ISO) belongs to a family of drugs called retinoids. It is the most effective drug prescribed by dermatologists for the treatment of the inflammatory disease, acne vulgaris. A significant barrier to the use of ISO has worries regarding its adverse effect profile. Despite the well-recognized reproductive toxicity and teratogenicity in females, there is no warning related to the use by male patients in the medication prospectus. Current data on the effects on human male fertility is contradictory and inconclusive. Objectives: This study was undertaken to investigate the potential effects of ISO oral doses in the Sprague–Dawley male rat germ cells using the sperm morphology assay. Also, the serum levels of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured. Methods: The rat groups were given varying ISO doses via gastric gavage for seven consecutive days. The epididymis sperm specimens were microscopically examined for the following reproductive toxicity parameters: sperm concentration, examined viability, motility, and morphology. The serum FSH, LH, and testosterone levels were measured by using the corresponding enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed statistically by one-way analysis of variance (ANOVA) followed by the Tukey test at P ≤ 0.05 significance level. Results: The results indicated that the drug did not significantly increase the sex hormone levels but notably affected both the sperm quantity and quality. Conclusion: These observations suggest that ISO was reprotoxic, and future therapies should be further reassessed.

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

“…The relatively prompted level of expression of E2F4 verified in the testicular epithelium during spermatogenesis was in general agreement with what was reported before. 12,28 It was consistent with its function identified concerning expression patterns. 31 As suggested previously, the relationship between E2F4 expression and tissues that are actively multiplying like testis proposes two conceivable alternative explanations.…”

“…The results of the present research, added to those published before, 28 suggest that subchronic exposure to high-dose therapy of ISO may have severe side consequences on the spermatogenic cycle as well as on liver and kidney functions. This outcome diverges from some reports on the protective effects of ISO against kidney damage in a rat model 6 and the amendment of sperm production in men with infertility.…”

“…5 Cytotoxicity may be followed by cell death, apoptosis, or necrosis, 29 leading to a drop in germinal epithelial cells. The results gained for the percentages of sperm aberrations 28 permit establishing a connection between the seminiferous epithelium changes and the decrease in the epididymal weight. 30 These workers demonstrated that ISO lowered the reproductive organ's weight and the amount of Sertoli and Leydig cells.…”

“…This microenvironment shields the developing cells in seminiferous tubules from obstructing molecules. 26 In rats, ISO has been established to be reprotoxic; 27,28 administration of a high dose of ISO caused statistically significant declines in rat sperm motility, sperm viability, seminiferous tubule thickness, and germinal epithelium. Also, ISO was cytogenotoxic.…”