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

Abstract

Background:Methamphetamine (MA) was shown to have harmful effects on male reproductive system. Objective:To investigate probable effects of daily administration of MA on sperm parameters and chromatin/DNA integrity in mouse.Material and Methods:Thirty-five NMRI male mice were divided into five groups including low, medium, and high dosage groups which were injected intraperitoneally with 4, 8 and 15 mg/kg/day for 35 days, respectively. Normal saline was injected in sham group and no medications were used in control group. Then, the mice were killed and caudal epididymis of each animal was cut and placed in Ham’s F10 medium for sperm retrieval. To evaluate sperm chromatin abnormalities, the aniline blue, toluidine blue and chromomycine A3 were used. For sperm DNA integrity and apoptosis, the acridine orange, sperm chromatin dispersion, and TUNEL assay were applied. For sperm morphology, Papanicolaou staining was done Results:Normal morphology and progressive motility of spermatozoa decreased in medium and high dosage groups in comparison with the control group (p=0.035). There was a significant increase in rate of aniline blue, toluidine blue, and chromomycine A3 positive spermatozoa in high dosage group. In a similar manner, there was an increase in rates of acridine orange, TUNEL and sperm chromatin dispersion positive sperm cells in high dosage group with respect to others.Conclusion:MA abuse in a dose-dependent manner could have detrimental effects on male reproductive indices including sperm parameters and sperm chromatin/DNA integrity in mice.

Assessment of sperm morphology, chromatin integrity, and catSper genes expression in hypothyroid mice

“…In accordance with our findings, the morphological deformities of sperm in the tail region of hypothyroid and hyperthyroid men have been reported [37]. Moreover, inconsistent with our results, several experiments have shown that administration of methamphetamine, gold nanoparticles, and acrylamide leads to a decrease in the sperm normal morphology [22,26,31]. To our knowledge, the present study was the first report that showed the relationship between the abnormal sperm chromatin quality and hypothyroidism.…”

“…Finally, the slides were cleared with xylene and mounted with Entellan (Merck, Germany). After imaging with Olympus (BX51, Japan) light microscope at ×1000 magnification objective lenses (UPlan FI, Japan), normal and abnormal forms of sperm morphology were determined [31].…”

“…Besides, today, it is well known that the quality of sperm chromatin can be a good biomarker in the evaluation of the male fertility potential. During spermatogenesis, sperm chromatin is tightly compacted by replacement of histones with protamines, and this nuclear compaction preserves sperm DNA from external damages such as oxidative stress [26,30,31,39]. Oxidative stress known as one of the important causes of male infertility arises from exposure to high levels of reactive oxygen species (ROS).…”

“…ROS as by-products of tissue metabolism is normally scavenged by physiological antioxidants defense systems. In reproductive system, intrinsic antioxidants maintain the functional integrity of the cell membrane, spermatogenesis, sperm morphology, and motility [7,11,31,32]. There are increasing bodies of evidence that show hypothyroidism is associated with the high production of ROS in testis.…”

“…There are increasing bodies of evidence that show hypothyroidism is associated with the high production of ROS in testis. It is well known that high amounts of ROS negatively affect the quality of sperm DNA as well as sperm morphology and motility [11,22,31,32,38]. This study was conducted to determine the effect of hypothyroidism on the alteration of sperm chromatin, sperm morphology, and CatSper 1 and CatSper 2 genes expression.…”