Repeated inhalation of crack-cocaine affects spermatogenesis in young and adult mice

Abstract

To investigate the effects of repeated crack-cocaine inhalation on spermatogenesis of pubertal and mature Balb/c mice, ten young (Y(ex)) and ten adult (A(ex)) Balb/c mice were exposed to the smoke from 5 g of crack with 57.7% of pure cocaine in an inhalation chamber, 5 days/week for 2 months. The young (Y(c)) and adult (A(c)) control animals (n = 10) were kept in a specially built and controlled animal house facility. The morphologic analysis of both testes of all animals included the analysis of quantitative and qualitative histologic parameters to assess the effect of crack-cocaine on spermatogenesis and Leydig cells. Apoptosis was determined by immunolabeling with caspase-3 antibodies. Compared to the Y(c) animals, Y(ex) animals showed a significant reduction in the number of stage VII tubules per testis (p = 0.02), Sertoli cells (p < 0.001) and elongated spermatids (p = 0.001). Comparisons between the Y(ex) and A(ex) groups identified a significant reduction in the number of Sertoli cells (p < 0.001) and round spermatids (p < 0.001) in the Y(ex) group and a significant increase in apoptotic Leydig cells (p = 0.04) in the A(ex) group. The experimental results indicate that crack-cocaine smoke inhalation induced spermatogenesis disruption in chronically exposed mice, particularly in pubertal mice.

A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine

“…The negative pressure allowed the use of less drug than required by other devices, and exposure to the smoke of 250 mg of crack cocaine achieved similar plasma cocaine concentrations as reported by Herculiani et al (2009) andPires et al (2012).…”

Psychostimulant-Induced Testicular Toxicity in Mice: Evidence of Cocaine and Caffeine Effects on the Local Dopaminergic System

“…Importantly, the caffeine-cocaine combination induced lower DAZL-positive cell counts than cocaine-alone, indicating that caffeine was able to potentiate cocaine-induced germ cell loss. Accordingly Pires et al [ 48 ] reported that crack cocaine induced a reduction in the number of germ cells and Sertoli cells, leading to a reduction of the tubular diameter in mouse testis. However, we did not detect changes in FSHR protein expression, which is considered a marker of Sertoli cell number [ 44 ], probably indicating that Sertoli cell number may not be altered under our experimental conditions.…”

“…In particular, lipid peroxidation is considered to be the main mechanism by which ROS can induce tissue damage leading to impaired cellular function in the testis [ 52 , 53 ]. It has been reported that prolonged exposure to cocaine leads to increased ROS production, germ cell apoptosis, and fibrosis of the seminiferous tubules in the male rat [ 54 , 6 , 51 , 48 ]. Accordingly, we observed that cocaine treatments induced TBARS production indicative of increased lipid peroxidation.…”

“…Additionally, there is evidence that caffeine can scavenge ROS and protect against lipid peroxidation [ 55 , 56 ]. It is important to point out that other reports using different cocaine protocols showed reduced glutathione peroxidase levels [ 6 ], and increased expression of pro-apoptotic markers such us DNA fragmentation, cytochrome c, caspase 3, and caspase 9 in rodent testis [ 57 , 51 , 48 ]. We did not observe changes in BAX expression in the cocaine-only treatment group, which could be related to the lower cocaine doses used in this study compared to previous ones [ 6 , 57 , 51 ].…”

Chronic exposures and male fertility: the impacts of environment, diet, and drug use on spermatogenesis

“…Inhaled crack cocaine decreases testicular volume, numbers of Sertoli cells, and impairs spermatid differentiation in mice (Pires et al ., ). Chronic cocaine administration decreases seminiferous tubule diameter and spermatid count in rats (George et al ., ), and has been shown to decrease cAMP responsive element modulator (CREM) expression, which is essential for spermatogenesis (Li et al ., ).…”