Induction of Testicular Damage by Daily Methamphetamine Administration in Rats

Abstract

Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

“…The hypothalamic-pituitary-gonadal axis can be affected by many factors. Chemicals including drugs can decrease fertility and even lead to infertility in both males and females by disrupting the normal function of this axis [41]. It has been shown that antiepileptic drugs also influence hypothalamic-pituitary-gonadal axis and cause reproductive dysfunction [6, 36–38, 42–44].…”

“…A decrease in serum LH levels can directly decrease the testosterone production from Leydig cells [40]. Additionally, a decrease in testosterone levels is considered to be related to the severity of spermatogenic cell damage and disruptions in spermatogenesis, and can therefore cause reproductive dysfunction [40, 41]. Histopathological findings in our study also indicated that vacuolization that was mildly observed in our low-dose group was followed by cellular swelling, spermatid damage, degeneration, and necrosis becoming more pronounced in a dose-dependent manner.…”

GABAergic Alterations in the Rat Testis after Methamphetamine Exposure

“…Several studies have reported impairments of testis, sperm quality and endocrine disruption after METH exposure 7-10. Apoptosis of Leydig cells and a decrease of serum testosterone were found 8, 9. Furthermore, METH administration resulted in the reduction of progesterone and estrogen receptor expression in testis 9.…”

Administration of high dose of methamphetamine has detrimental effects on sperm parameters and DNA integrity in mice

“…It is also suggested that MA affects male reproductive function at multiple levels due to its effects on the endocrine control of spermatogenesis (13, 14). Recently, it has been reported that MA decreases normal sperm morphology and count, as well as increase apoptotic cells in seminiferous tubules (15, 16). In a study conducted by Zuloaga et al , histopathological and histomorphometric alterations in seminiferous tubules have been reported in MA-treated animals (17).…”