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Food and Chemical Toxicology : An... Dec 2023Previous researches have demonstrated that the silica nanoparticles (SiNPs), which are widely used in all aspects of life, are hazardous to the male reproductive system....
Previous researches have demonstrated that the silica nanoparticles (SiNPs), which are widely used in all aspects of life, are hazardous to the male reproductive system. However, the cellular and molecular mechanism underlying SiNPs toxicity to the epididymis remain unclear. In this present study, a total of 60 male mice were separated into 4 groups and then treated to SiNPs for 7 consecutive days at a dose of 0, 2.5, 10, and 20 mg/kg body weight. The results showed that SiNPs could alter the histological structure of epididymis and induce sperm granuloma formation, leading to decreased sperm quality and quantity. In addition, the ultrastructure and permeability of blood-epididymal barrier (BEB) were impaired after exposure to SiNPs, and a significant downregulation of integral membrane proteins at the BEB was detected. SiNPs were also found to raise the percentage of macrophages in the epithelium and interstitium of the epididymis, followed by increased expression of pro-inflammatory molecules including TNF α, IL-1β, and IL-6. Meanwhile, SiNPs induced oxidative stress in epididymis, as shown by the markedly elevated generation of reactive oxygen species (ROS) and malondialdehyde (MDA) and upregulated activity of superoxide dismutase (SOD). Further study showed that SiNPs activated the p38 MAPK signaling pathway, which accelerated clathrin-mediated endocytosis of integral membrane proteins and perturb vesicular trafficking. Taken together, exposure to SiNPs could induce sperm granuloma formation and impair the integrity of BEB in mice through activating the p38 MAPK pathway.
Topics: Animals; Male; Mice; Epididymis; Silicon Dioxide; Semen; Spermatozoa; Oxidative Stress; Nanoparticles; Membrane Proteins
PubMed: 37890760
DOI: 10.1016/j.fct.2023.114113 -
Journal of the American Association For... Nov 2023Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have...
Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have potential consequences such as sperm granulomas and long recovery time. Deslorelin is a gonadotropin-releasing hormone agonist that temporarily and reversibly suppresses sex hormone secretion. Our goal in this study was to investigate the effects of deslorelin on testosterone secretion and testicular volume in male rhesus macaques (). Male macaques ( = 4) each received two, 4.7-mg deslorelin implants subcutaneously in the interscapular region. Serum testosterone and testicular volume were then monitored at specific time points until 10 mo after treatment. Testosterone suppression was defined as testosterone levels lower than 0.6 ng/mL for a sustained period of at least 30 d. After implantation, mean testicular volume was significantly reduced by day 121. Testosterone suppression was observed in all subjects. However, the time from implantation to testosterone suppression and duration of suppression varied. Two macaques were hormonally suppressed by day 26 after implantation and remained suppressed for at least 6 mo. The other 2 macaques were hormonally suppressed by 2 mo after implantation; of these two, one remained suppressed for 70 days while the other was suppressed for at least 245 days. We conclude that deslorelin can safely suppress testosterone secretion in male rhesus macaques, but individual variation in onset and duration of action should be considered when establishing reimplantation time points and potential return to reproductive activity.
Topics: Male; Animals; Testis; Gonadotropin-Releasing Hormone; Macaca mulatta; Testosterone; Semen; Drug Implants; Triptorelin Pamoate
PubMed: 37844997
DOI: 10.30802/AALAS-JAALAS-22-000116