Dose-Dependent Reproductive Toxicity of Oxandrolone in Adult Male Wistar Rats: Endocrine Disruption, Spermatogenic Impairment, and Histopathological Alterations

Abstract

Objective: This study aimed to investigate the effects of repeated intraperitoneal administration of oxandrolone on reproductive hormones, epididymal sperm parameters, and testicular histopathology in adult male Wistar rats.
Materials and Methods: Twenty-four adult male Wistar rats, aged 10–12 months, were randomly divided into four groups (n = 6 per group). The control groups received distilled water or dimethyl sulfoxide (DMSO), whereas the treatment groups received oxandrolone at doses of 0.82 and 1.62 mg/kg body weight by intraperitoneal injection once daily for four weeks. Serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using enzyme-linked immunosorbent assay (ELISA). Epididymal sperm count was assessed using a Neubauer hemocytometer, and sperm abnormalities were evaluated following eosin staining. Testicular tissues were examined histologically using hematoxylin and eosin (H&E) staining.
Results: Oxandrolone administration resulted in a significant, dose-dependent reduction in serum testosterone, LH, and FSH levels compared with the control groups Oxandrolone-treated rats also exhibited a reduction in epididymal sperm count and an increase in the frequency of sperm morphological abnormalities. Histopathological examination revealed degeneration of the seminiferous tubules, sloughing of the germinal epithelium, depletion of spermatogenic cells, nuclear hypochromasia, and a reduction in the number of mature spermatozoa. These histological alterations were more pronounced in rats receiving the higher oxandrolone dose.
Conclusions: Repeated intraperitoneal administration of oxandrolone adversely affected male reproductive function by suppressing reproductive hormone levels, impairing sperm production and morphology, and inducing structural alterations in the testes. The findings suggest that prolonged or inappropriate oxandrolone exposure may compromise male fertility and highlight the importance of appropriate medical supervision during its therapeutic use