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Published on: October 2, 2018
Antispermatogenic and antifertility effects of 20,25-diazacholesterol dihydrochloride in mice
Shio K Singh1, Sumana Chakravarty
1Department of Zoology, Banaras Hindu University, Varanasi 221005, India. shioks@banaras.ernet.in
Abstract:
The effect of intraperitoneal administration for 28 days of 10, 20, and 30 mg/kg body weight per day of 20,25-diazacholesterol dihydrochloride (SC 12937), a hypocholesterolemic agent, on the testis of Parkes (P) strain mice was investigated. Histologically, testes in mice treated with 10 or 20 mg/kg body weight of SC 12937 showed non-uniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; the affected tubules showed intraepithelial vacuolation, occurrence of giant cells, exfoliation of germ cells, and marginal condensation of chromatin in round spermatids. In both dosage groups, only 11-12% of the seminiferous tubules were affected, and no significant differences were found in the frequency of affected tubules between the two groups. By contrast, testes in mice treated with 30 mg/kg body weight of the drug exhibited a degenerated appearance of germ cells in all seminiferous tubules. The treatment also had adverse effects on motility, viability, morphology, and number of spermatozoa in the cauda epididymidis, and on fertility. Even 56 days after drug withdrawal, the above parameters remained markedly affected. Our results thus suggest that SC 12937 treatment causes antispermatogenic and antifertility effects in P mice and that the effects are not reversible up to 56 days after drug withdrawal. This compound may prove useful in the control of rodent populations.
Insights
The hypocholesterolemic agent 20,25-diazacholesterol dihydrochloride (SC 12937) caused significant antispermatogenic and antifertility effects in mice. These adverse effects on sperm parameters and fertility were not reversible even 56 days after drug withdrawal.
Area of Science:
- Reproductive Toxicology
- Pharmacology
- Endocrinology
Background:
- The hypocholesterolemic agent 20,25-diazacholesterol dihydrochloride (SC 12937) is known to lower cholesterol levels.
- Investigating the potential reproductive toxicity of SC 12937 is crucial due to its pharmacological activity.
Purpose of the Study:
- To evaluate the effects of SC 12937 on the testes and fertility of Parkes (P) strain mice.
- To determine the reversibility of any observed adverse effects after drug withdrawal.
Main Methods:
- Parkes (P) strain mice were administered intraperitoneally with 10, 20, or 30 mg/kg/day of SC 12937 for 28 days.
- Histological examination of testes, and assessment of sperm motility, viability, morphology, and count were performed.
- Fertility trials were conducted, and effects were evaluated up to 56 days post-treatment.
Main Results:
- SC 12937 induced dose-dependent degenerative changes in seminiferous tubules, including vacuolation and germ cell exfoliation.
- The highest dose (30 mg/kg) resulted in widespread germ cell degeneration in all tubules.
- Significant adverse effects on sperm parameters and fertility were observed, persisting for at least 56 days after SC 12937 withdrawal.
Conclusions:
- SC 12937 exhibits potent antispermatogenic and antifertility properties in mice.
- The observed reproductive toxicity is not reversible within 56 days of drug cessation.
- SC 12937 demonstrates potential for use in rodent population control due to its lasting antifertility effects.
