Light and electron microscopic studies of the effect of alprazolam on the testicular tissue of mice

Alprazolam (8-chloro-1-methyl-6-phenyl-4H-s-triazolo, 4,3-á) is a benzodiazepine derivative used in the treatment of panic attacks, generalized anxiety, and depression. The present study aimed to assess the reproductive efficiency of male mice after exposure to different doses of alprazolam (ALP). This was done by estimation of serum testosterone hormone, sperm morphology, histopathological and ultrastructural investigations of the testicular tissue. Sixty male mice were divided into four experimental groups (15 mice/group); the control and three experimental mice groups. The control mice were given no treatment. The experimental mice were received daily oral by gavage three different dose levels of ALP (0.5, 1.5 and 4.5 mg/kg bw) for three months. The obtained results revealed a decrease in the body weight gain, absolute and relative testes and epididymal weights in experimental-treated group. Significant findings were detected in higher dose treatment. Also, there was dose-dependent decrease of serum testosterone hormone of ALP-treated mice, being significant at high dose level. Following investigating sperm anomalies, experimental groups exhibited significant increase. The prominent sperm deformities were as such the detached head, the amorphous head and the highly folded tail. The applied drug treatment possessed testicular damage including atrophy of seminiferous tubules (ST) and reduction of spermatogenic cells. Furthermore, detachment and sloughing of spermatogenic epithelium were a marked increase of inactive ST with degenerated spermatids, spermatozoa and severe Leydig cells. Ultrastructurally, the cytoplasm of spermatocytes showed marked vacuolation and the nuclei appeared with convoluted nuclear envelope and disintegration of their nuclear chromatin. The mitochondria in secondary spermatocytes contained wide intercristae apaces and they formed dense masses of intermitochondrial cement. Accumumulation of myelin figures were observed in the cytoplasm of these cells. Spermatids had deformed nuclei and irregularly-shaped acrosomes. In conclusion, it was found that treatment with alprazolam produced pronounced male reproductive toxicities in testes and epididymis associated with increased incidence of sperm shape abnormalities and a decrease of testosterone hormone. Also, ALP caused degeneration in seminiferous tubules, depletion of germinal epithelium, intercellular disassociation of germ cells, along with disruption in germ cell arrangement, and an increase in Leydig cells damage.