Antispermatogenic and antifertility effects of 20,25-diazacholesterol dihydrochloride in mice.

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.

Diazacholesterol-induced ichthyosis in the hairless mouse. Assay for comparative potency of topical retinoids.

Although the new synthetic retinoids are effective when administered systemically, they have not been shown to be effective as topical agents. We compared the topical activity of six synthetic retinoids (two arotinoids, etretinate, all-trans- and 13-cis-tetrazole-retinamide, isotretinoin, and tretinoin) on tail skin in the diazacholesterol-fed mouse model of ichthyosis. Responses were assessed clinically and by measurement of stratum corneum thickness. Although the arotinoids dramatically reduced scaling, they were toxic at concentrations above 0.1%, as was etretinate at 1.0% or greater. Lower concentrations were effective without producing local or systemic toxic reactions. Clinical responses were paralleled by equivalent decrements in stratum corneum thickness, which also permitted quantitative comparisons. The order of potency for the retinoids was as follows: arotinoids, etretinate, tetrazole-retinamides, tretinoin = isotretinoin, vehicle. These results demonstrate that (1) the synthetic retinoids hold promise as topical agents; (2) irritation is not an absolute requirement for topical retinoid activity; and (3) the diazacholesterol-fed mouse offers a new assay of topical retinoid potency in a well-defined animal model of ichthyosis.