Evaluation of histopathologic and histomorphometric changes of testicular tissue and gonadotropin levels following consumption of methylphenidate in male mice.

BACKGROUND/AIM: One of the most common psychiatric disorders in children is attention-deficit/hyperactivity disorder, which is treated extensively by methylphenidate. This study investigates the assessment of the effects of methylphenidate on histopathologic and histomorphometric changes of the testes and serum levels of gonadotropin in mice. MATERIALS AND METHODS: In this study, 36 adult male mice were used. After determining their body weights, the animals were divided randomly into 2 experimental groups and 1 control group. The experimental groups received methylphenidate (2 and 10 mg kg(-1) day(-1)) via gavage for a period of 40 days. After evaluation of body weight, general anesthesia was used for taking blood samples from the heart in order to measure testosterone and levels of gonadotropin in serum. For the purpose of weighing the bodies and measuring the thickness of the germinal epithelium, the testes were removed and the possibility of any pathological changes was considered. RESULTS: The results showed that methylphenidate could decrease the thickness of the germinal epithelium and body weight significantly, and could increase the levels of spermatogonia and serum gonadotropins and testosterone. Histopathological changes were also seen for vascular dilatation and congestion in interstitial tissue. CONCLUSION: Our findings demonstrated that administration of methylphenidate in adulthood may have an effect on spermatogenesis due to the influence of gonadotropin hormones on testis function.

The effect of chronic administration of methylphenidate on morphometric parameters of testes and fertility in male mice.

BACKGROUND: Due to common use of methylphenidate (MPH) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and the role of the reproductive system in the production of gametes, studying the effects of this medication on the morphometry of testes, serum testosterone concentration, leydig cells function, and fertility rate was the aim of this study. METHODS: Twenty seven male mice (Balb/C), eight weeks old, were randomly divided into one control and two treated groups. After weighing the mice, the treated groups received MPH (produced in Novartis company) at the doses of 2 mg/kg and 10 mg/kg for 40 days. The control group received only normal saline. Subsequently, after weighing the animals, the weights of testes, dimensions of the testis, and the serum testosterone concentration were measured in six mice belonging to each group. After tissue processing, the samples were stained with hematoxylin and eosin, then the leydig cells were counted. In order to assess male fertility in each group, 3 male mice were chosen and each of them was kept with three female mice in a separate cage. After 10 days, the fertility rates of the male mice were determined by counting the number of embryos in uterus and the corpora lutea in their ovaries. RESULTS: The results of this study revealed that prescription of different doses of MPH can cause a significant decrease of the body weight. It reduces the number of leydig cells, too (p<0.01). Moreover, serum testosterone concentration (67.72±8.24 ng/ml in control group and 0.302±0.416 ng/ml after treatment with 2 mg/kg/day MPH) and fertility rate (95.42%±4.68% in control group and 64.96%±18.51% after treatment with 2 mg/kg/day MPH) of the male mice declined significantly in the treated groups compared with the control group (p<0.01), but it did not cause any changes in the weight or morphometric parameters of testes. CONCLUSION: The results of this study confirmed that MPH can negatively affect serum testosterone concentration and fertility rate of the male mice by decreasing the number of leydig cells and reducing the body weight.